Undergraduates: Open Research Positions & Projects

Students: contact Dr. Anna Babakhanyan, Science Undergraduate Research advisor, to help identify research laboratories.
Faculty: if you are interested in posting your open research position, please contact  Dr. Anna Babakhanyan.

 

Paid Summer Research Opportunity: Texture analysis of radiography images to predict femoral fracture load, BIDMC, OrthoBiomechanics Lab, Posted May 14, 2018

Research Opportunity cryo-EM analysis of the structure of the hair-cell mechanotransduction channel, HMS Department of Neurobiology, Posted May 1, 2018

Undergraduate research opportunity on finding Alzheimer’s disease cure, MEEI, Posted April 9, 2018

Undergraduate Research Opportunity – Molecular Imaging, MGH, Posted April 3, 2018

Biomedical Engineering Summer Intern, Harris Orthopaedics Laboratory, Massachusetts General Hospital, Posted March 23, 2018

Undergraduate research opportunity at the Laboratory for Computational Neuroimaging, Martinos Center for Biomedical Imaging, MGH, Posted March 23, 2018

Undergraduate research opportunity, Cognitive Neuroscience Group, MGH Institute of Health Professions, Posted March 23, 2018

Undergraduate research opportunity in Mars science, Posted March 15, 2018

Undergraduate Researcher, Dr. Catherine Dulac, Harvard MCB, Posted Feb 20, 2018

Investigating the effects of weather on surface air quality, SEAS, Posted Feb 15, 2018

Immunology Undergraduate Research, Wucherpfennig lab, Dana-Farber Cancer Institute, Posted Feb 15, 2018

Undergraduate Position, Dr. Aizenberg Laboratory, SEAS, Posted Feb 2, 2018

Undergraduate research opportunity, Dr. Balskus Laboraotry, Posted Jan 30, 2018

Center for Depression, Anxiety and Stress Researc, Dr. Pizzagalli Lab, Center for Depression, Anxiety, and Stress Research, McLean Hospital / Harvard Medical School, Posted Jan 4, 2018

Uncovering novel etiologies for male infertility, Dr. Morton Lab, Brigham and Women’s Hospital, Boston, MA, USA , Posted Jan 4, 2018

100 Million years of Fish in the Sea, Dr. Sibert Lab, Department of Organismic and Evolutionary Biology AND Department of Earth and Planetary Sciences, Posted Jan 4, 2018

Regulation of cholesterol metabolism in diabetes, Dr. Biddinger Lab, Department of Medicine/Division of Endocrinology, Boston Children's Hospital Harvard Biological and Biomedical Sciences Program, Harvard Medical School , Posted Jan 4, 2018

 

 

Posted May 1, 2018

Research Opportunity cryo-EM analysis of the structure of the hair-cell mechanotransduction channel, HMS Department of Neurobiology

Within the inner ear are fast, sensitive receptor cells, working on a scale of microseconds and nanometers to convert the mechanical stimulus of sound into electrical signals that the brain can understand. In recent years, this process has become better understood, as many proteins involved in the submicroscopic mechanotransduction complex have been identified. Our group in the Neurobiology Department at Harvard Medical School is working to understand the complex, with a combination of electrophysiology, 3D electron microscopy, biochemistry, and single-protein mechanics. We have  openings for one or two students to join this effort.

In one project, we are working to solve the atomic structure of the protein that forms the ion channel of the complex. This project involves synthesizing and purifying protein, preparing for cryo-electron microscopy, and analysis of the single-protein images. Students will gain experience in cell culture, biochemistry, protein engineering and structural biology.  They will help screen for conditions that stabilize the ion channel in one conformation using different approaches and participate in cryo-imaging work.

In another project, we need to understand how the mechanotransduction proteins assemble into a functional complex. We use state-of-the-art biochemical and biophysical techniques such as biolayer interferometry, multi-angle light scattering, microscale thermophoresis and isothermal calorimetry, as well as more conventional methods like co-immunoprecipitation, to understand how different proteins interact with each other to form the mechanotransduction apparatus. Students will help us with DNA cloning, protein synthesis, and cell culture to generate a library of proteins. Students will then participate in the collection and analysis of biophysical and biochemical interaction data to generate an interaction model.

To apply, email: Dr. David P. Corey, Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, dcorey@hms.harvard.edu

 

Paid Summer Research Opportunity: Texture analysis of radiography images to predict femoral fracture load, BIDMC, OrthoBiomechanics Lab

 

If you're still looking for summer employment opportunities, the laboratory, the Center for Advanced Orthopedic Studies, is looking for a summer student. The lab (www.bouxseinlab.org/) is in the Orthopedics department at Beth Israel Deaconess Medical Center and Harvard Medical School. The lab is a highly interdisciplinary environment, with biomedical engineers, biologists and medical professionals working together. Please read below for project details and email the post-doc running the project (Dr. Fjola Johannesdottir) with your resume if you are interested in the position. The starting date is flexible. The mentor will introduce the student to medical processing and provide support throughout course of the project. The mentor will have weekly meetings with the student to ensuring that progress is made and to help resolving problems if any.

Mentors: Mary L. Bouxsein and Fjola Johannesdottir

Project description: Osteoporosis is common, as 1 in 3 women and 1 in 5 men aged over 50 will break at least one bone due to osteoporosis. Osteoporosis is a disease that is characterized by reduced bone mass and impaired architecture which causes bones to become weak and brittle. The current clinical standard for fracture risk assessment is bone mineral density (BMD) by dual energy absorptiometry (DXA), although half of all fractures occur in those who do not have osteoporosis by BMD testing. Thus, new methods are needed to identify those at high risk for fracture so that they can be offered therapies to reduce their risk of fracture. DXA measurements are assessments of bone quantity and do not provide information on impaired bone architecture that is associated with bone fragility. Radiography images have sufficient spatial resolution to enable assessment of bone structure by applying texture analysis. The purpose of this study is to determine if gray level co-occurrence (GLCM) textural features (Haralick 1973) from plain hip radiography combined with BMD predict femoral failure load better than BMD alone. The student participating in this project will gain a complete understanding of how to perform textural analysis using GLCM and exposure to all related Matlab tools while being introduced to medical image processing and the clinical problem of fragility fractures. The results of this research experience are the implementation of a statistical method to medical imaging. Coding skills are required (being familiar with Matlab is preferred).

Email Fjola Johannesdottir (fjohanne@bidmc.harvard.edu) with your resume if you are interested.

 

 

Posted April 9, 2018

 

Undergraduate research opportunity on finding Alzheimer’s disease cure, MEEI

PI name: Joseph F. Arboleda-Velasquez, M.D., Ph.D.

Department: Ophthalmology

Contact Information: joseph_arboleda@meei.harvard.edu

Location: Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114. Two blocks from the MGH T-stop on the Red Line.

Description of the project and duties: Through genetic studies we identify gene candidates capable of modifying the start and progression of symptoms in individuals predetermined to suffer from Alzheimer’s disease. We test the ability of these gene mutations to modify molecular and cellular changes associated with Alzheimer’s disease in vitro and in vivo. Students will have the opportunity to learn and conduct studies of protein aggregation and cellular dysfunction relevant to Alzheimer’s disease.

Skills required. The students are not expected to have laboratory skills but will be expected to learn fast and be self-motivated.

Learning outcome: students will learn to conduct protein aggregation studies, circular dichroism, western blot, cell culture, cell death assays, experimental design, and data analysis and presentation. Most importantly, students will be encouraged to love what they do and work hard towards our goal of finding a cure for Alzheimer’s disease.

Number of hours students are expected to work: hours will be flexible but it will be important that the student can commit for Summer 2018 and hopefully continue through the year.

Mentoring: Dr. Arboleda-Velasquez will personally mentor the student via meetings and via participation in group meetings.

Does laboratory provide any funds to pay student’s stipend?

The lab will fund reagents for the project but no the stipend. Dr. Arboleda-Velasqeuz will support fellowship applications and exceptcional students may be considered for funding after a training period. Students are encouraged to apply to the HCRP and other fellowships or register for a research course credit.

What information students need to submit and contact information for submitting this information:  Please email me with a stamen of interest.

 

Posted April 3, 2018

Undergraduate Research Opportunity – Molecular Imaging, MGH

PI: Pedro Brugarolas, PhD, Assistant Professor of Radiology, Harvard Medical School and Gordon Center for Medical Imaging, Massachusetts General Hospital

Contact info: Pedro Brugarolas, PhD  pbrugarolas@mgh.harvard.edu

Lab location: Massachusetts General Hospital, 55 Fruit St, Bulfinch 051, Boston, MA 02114

Lab website 

Department website

Description of the project and duties:

The candidate will work alongside the PI and a postdoc producing and characterizing new radioactive small molecules for medical diagnostics. The goal of the lab is to develop new radiotracers for positron emission tomography (PET) and characterize them in animal models of disease. See Development of a PET tracer for potassium channels to image demyelination for an example of the work.

Requirements: 1 semester of general chemistry with lab. Desired: 1 semester of organic chemistry with lab. Previous research experience in a chemistry or biochemistry lab.

Learning outcome: Students will learn the fundamentals of radiochemistry and PET imaging. Students will learn how to work safely in a radiochemistry lab. Students will also learn methods to generate and characterize small molecules including HPLC, NMR, etc.

Number of hours students are expected to work, length of the project: Term and hours are negotiable. Preference will be given to students interested in working 12+ months to allow them to master techniques and produce results. During summers, students are encouraged to spend 25+ hours a week in the lab. During the school year, students are encouraged to attend lab meetings and spend time in the lab as their schedule permits (minimum 8h/week).

Mentoring: Students will work alongside a postdoc (1 student per postdoc). As they become proficient in certain tasks, students will gain independence. Students may not work alone in the lab. Postdoc will provide day-to-day supervision. PI will meet with the student regularly (once or twice a week) to review progress and assist with the research experiments.

Funding: Students are encouraged to apply to the HCRP and other fellowships or register for a research course credit. Limited funding may be available from the lab.

Interested: Please send CV/resume and interests to Dr. Pedro Brugarolas at pbrugarolas@mgh.harvard.edu

 

Posted March 23, 2018

 

Biomedical Engineering Summer Intern, Harris Orthopaedics Laboratory, Massachusetts General Hospital

Harris Orthopaedics Laboratory (HOL) at the Massachusetts General Hospital is seeking for two rising seniors for a 8-10 week paid summer research internship, with concentrations preferably in Chemical/Biomedical Engineering or Chemistry to begin in June.

Our investigators are authors of over 600 publications, including some of the 100 most frequently cited papers in orthopedic surgery. The laboratory’s more than 75 patents worldwide, some of which have led to licensed technologies, have positively impacted the quality of life for over 7 million patients. Our research interns and technicians have the opportunity to contribute to ongoing translational research projects focused on improving materials in orthopedics to allow for a better quality of life for patients. Our members gain invaluable research experience usually prior to entering medical or graduate school. Previous technicians in our laboratory have authored articles in several peer-reviewed journals, presented their research at conferences, and gone on to medical school at Harvard, Tufts, Case Western, and Arizona or to graduate school at Dartmouth, UT, Georgia Tech, UPenn, and UVA.

Interested candidates: Contact Slav Lerner (Manager), Harris Orthopaedics Laboratory, Massachusetts General Hospital 
55 Fruit St.,  Jackson 1121B, Boston, MA 02114  www.harrisortholab.org

 

 

Undergraduate research opportunity, Cognitive Neuroscience Group, MGH Institute of Health Professions

PI: Dr. Yael Arbel, co-director Cognitive Neuroscience Group, Department of Communication Sciences and Disorders, MGH IHP, 79 13th Street, Boston, MA 02129. https://www.mghihp.edu/research/cognitive-neuroscience-group

A research assistant is needed for an NIH funded project focusing on the neural function associated with cognition and learning in typically developing children and children with developmental language disorders. The study involves the recording and analysis of Event Related Potentials (ERPs) extracted from EEG recorded from the scalp, and the administration and analysis of cognitive and language tests.

Duties: The research assistant will be involved in all aspects of data analysis: scoring and analysis of behavioral data as well as EEG signal processing. EEG signal processing will include the use of Matlab based tool boxes for artifact detection/correction, latency jitter correction, and Principal Component Analysis (PCA).

Skills required: The RA must have experience with Matlab and PCA. The RA should also have the ability to create scripts in Excel (or using other tools) for the purpose of data analysis. Preferred skills include: signal processing, statistical analysis using SPSS or R, and programing. No research experience is required.

Learning outcome: The RA will receive training in behavioral and EEG data collection and data analysis. Training in eye-tracking data acquisition and analysis is also possible. The RA will participate in weekly lab meetings that will include presentations by PIs, and students at all levels (PhD, graduate, undergraduate). The RA will gain understanding of research design related to the study of learning in individuals with typical and atypical cognitive profiles. The RA will have the opportunity to present at the biweekly CNG meetings and to participate in scientific writing.

The RA is expected to work 20 hours per week (preferably 3-4 days a week) for 3 months

Mentoring: The RA will be mentored by the PI, Dr. Arbel, and her research coordinator, and will interact with other CNG members in training, meetings, and data collection sessions. The RA will attend weekly lab meetings, and weekly mentorship meetings with the PI.

Dr. Arbel will provide funds to support one RA for a period of 3 months. However, additional RA positions are available for students who receive funds through the HCRP or other fellowships.

Please submit a cover letter and a CV to Dr. Arbel at yarbel@mghihp.edu

 

 

Undergraduate research opportunity at the Laboratory for Computational Neuroimaging, Martinos Center for Biomedical Imaging, MGH

PI: Anastasia Yendiki, Ph.D.
Martinos Center for Biomedical Imaging
149 13th St. Suite 2301
Charlestown, MA 02129
ayendiki@mgh.harvard.edu
http://scholar.harvard.edu/a-y

The student researcher will contribute to a project that aims to map connections in the human brain, based on a combination of in vivo diffusion MRI brain scans with prior information from microscopic resolution ex vivo MRI and optical imaging. Brain pathways will be labeled manually to produce training data for an automated image analysis algorithm. Algorithms developed by our team learn the anatomical neighborhood of the pathways from such training data and then reconstruct the same pathways automatically in novel data sets. Depending on the student researcher's interests and skills, the work can focus more on neuroanatomical exploration of the in vivo and ex vivo data, software development, or both.
Prior experience working in a Unix-based computer environment is desired but not required.
The student will gain experience in neuroanatomy and in the analysis of neuroimaging data. Depending on progress and interest, the student may also assist with preparing conference abstracts and publications.
Project duration and hours per week are negotiable.
The student will be mentored by Dr. Yendiki and a postdoctoral research fellow. There will be opportunities to participate in weekly group meetings, as well as receive one-on-one mentoring as needed.
Students are encouraged to apply to the HCRP and other fellowships or register for a research course credit.
Please email a resume and a short (one paragraph) description of your research interests and career goals to Dr. Yendiki (ayendiki@mgh.harvard.edu).

 

Posted March 15, 2018

UNDERGRADUATE RESEARCH OPPORTUNITY IN MARS SCIENCE
Dr. Mathieu Lapotre (mlapotre@fas.harvard.edu)
Department of Earth and Planetary Sciences, Harvard Museum of Natural History
http://www.mathieulapotre.com

The history of Mars is one of dramatic change that transformed a hospitable environment into the barren land we know today. Over the past few decades, several studies have used different lines of geologic evidence to propose that oceans once existed on Mars; however, whether the Martian climate ever allowed an ocean to be stable remains a subject of intense debate. In recent years, it was suggested [e.g., 1] that large boulder fields on Mars are evidence for giant tsunamis that were caused by meteor impacts into a large northern ocean. If proven true, these boulder deposits would represent unequivocal proof of an early Martian ocean.

We are looking for an undergraduate student interested in helping us prove or disprove that these boulders were eroded and deposited by giant Martian tsunamis. To do so, we expect the student to conduct a systematic morphometric characterization of the boulder deposits (sizes, shapes, orientations, etc.) around the speculated paleo-shoreline of the northern ocean.

No prior research experience is required.

Outcomes: The student will learn to work with space-exploration orbital data. Although we envision that the student will mostly perform the analysis with the ArcGIS software, we are open to creative suggestions from the student. If time permits, the student will start analyzing the collected data using, e.g., Matlab. The student will be involved in the writing of a scientific publication based on these data. 

Expected hours: 35 hours/week for ~6-8 weeks, preferably over July-August 2018 (negotiable).

Mentoring: Dr. Lapotre will be mentoring the student on an as-needed basis, with weekly meetings built-in the schedule. Further mentorship may be provided by Mark Baum (graduate student in EPS) and Prof. Robin Wordsworth (SEAS/EPS).

Funding: The students are encouraged to apply to HCRP (deadline: March 28!) or other fellowships, or register for research course credit (see https://uraf.harvard.edu/undergraduate-research). Please make sure to contact me anyway if these funding options fall through but you are still interested in pursuing the research project.

Applying: Please submit a CV and a short (< 1 page) letter to introduce yourself and tell us why you are interested in this research project (mlapotre@fas.harvard.edu).

Reference:

[1] Rodriguez et al. (2016), Tsunami waves extensively resurfaced the shorelines of an early Martian ocean. Scientific Reports, 6:25106, doi: 10.1038/srep25106.

 

Posted February 20, 2018

Undergraduate Researcher, Dr. Catherine Dulac, Harvard MCB

PI: Dr. Catherine Dulac, MCB, dulac@fas.harvard.edu, Biolabs 4017, https://www.dulaclab.com/ -- this will be the main site of work for the student

Aviv Regev, Broad Institute, 415 Main St -- there may be occasional work to be done at the Broad

 

Students will be conducting behavioral experiments in mice, measure mice hormone levels, and prepare samples for deep sequencing (both microbial DNA and neuronal RNA). If students wish, they will be taught computational skills to conduct their own analysis on the cluster.

Skills: Prior research experience is strongly preferable. Additionally, students with prior experience working with mice will be at an advantage.

Learning outcome: The student will be able to pose a scientific question, carry it out with the laboratory skills that s/he would learn, interpret results, and write. For those with a computational/quantitative leaning, they will be able to conduct data analysis in MATLAB and Python on the cluster and become a trained bioinformatician; however, this will be secondary to the wet-lab work.

During the term, students are expected to work 10-15 hours a week. During the summer, it would be 40 hours a week. The project is long-term, i.e. at least one year and ideally two.

Mentoring: Postdoc Hattie Chung will be mentoring the student. Student will meet with Hattie every 1-2 weeks to discuss progress.

The laboratory can fund the student, both during the term and summer, but they are still encouraged to apply for HCRP: https://lifesciences.fas.harvard.edu/research-opportunities

Please submit your resume highlighting prior lab experience with a brief description of your research interests to hchung@fas.harvard.edu

 

 

Posted Feb 15, 2018

Investigating the effects of weather on surface air quality, SEAS

Supervisor: Loretta J. Mickley, senior research fellow; Yang Li, postdoc fellow, SEAS
Location: Pierce Hall Lab website: http://acmg.seas.harvard.edu/

Our research focuses on chemistry-climate interactions in the troposphere.  We seek to understand how gases and particles affect climate and how climate change, in turn, can influence the composition of the atmosphere.  Our group analyzes observations from a range of sources (ground-based monitors, aircraft, and satellites) and conducts modeling studies of atmospheric chemistry and climate. Key topics for summer projects include investigating the effects of meteorology on wildfires, smog episodes, or dust storms. Interest in programming is essential, and some knowledge of statistics would be helpful.

Learning outcome: research skills including data analysis, presentation and scientific writing

Mentoring: meet 1-2 times per week
Funding: students are encouraged to apply for fellowships (PRISE, HCRP, email ababakhanyan@fas.harvard.edu for more info)
Please email your resume/CV and a short statement of interest to Dr. Mickley at mickley@fas.harvard.edu and Dr. Li at yangli@seas.harvard.edu.

 

Immunology Undergraduate Research, Wucherpfennig lab, Dana-Farber Cancer Institute

Mentors: Kai W. Wucherpfennig, MD, PhD Email: Wucherpfennig_Lab@DFCI.HARVARD.EDU http://t-cells-treating-cancer.dana-farber.org/

Cancer Immunology and Virology
Contact: Charles Thomas; Wucherpfennig_lab@dfci.harvard.edu
Dana-Farber Cancer Institute 1 Jimmy Fund Way, Smith Building Floor 7 Boston, Massachusetts 02115
Office: 617-582-8289      http://t-cells-treating-cancer.dana-farber.org/

The goal of this program is to create a cohesive immunology training program in which undergraduate students are prepared for entry into PhD programs in Immunology and the development of immunotherapies. Under the leadership of Dr. Wucherpfennig and his team, students will also gain invaluable experience and insight into experimental design, innovative techniques, and the path to publication within a prestigious research laboratory. By participating in this program, students will be given the opportunity to develop both the technical skills and scientific discipline integral to a successful career in Immunology. 

Requirements: No prior research experience is necessary. However, an interest in life sciences research, problem solving, and good communications skills are required.

Number of hours: 10 hours per week minimum. Duration is flexible, but longer commitments are preferred and highly encouraged to gain something from the program.

Mentoring: Mentoring will be primarily provided by graduate students and fellows of the Wucherpfennig lab. The student will meet with the PI regularly in bi-weekly meetings with the fellow and/or graduate student.

Compensation: This is primarily a volunteer position; however, funding options can be more thoroughly discussed during the interview process.

Applying: Interested students should email Charles Thomas a single PDF document with the below requirements (email: Wucherpfennig_Lab@DFCI.HARVARD.EDU):

  1. Cover Letter- Introduce yourself and describe your specific interests in immunology.
  2. Curriculum Vitae- Please include relevant coursework, GPA, prior lab experience (if any), and other extra-curricular activities.

 

 

 

Posted Feb 2, 2018

Undergraduate Position, Dr. Aizenberg Laboratory, SEAS

Principal Investigator 
Prof. Joanna Aizenberg
Amy Smith Berylson Professor of Materials Science 
Professor of Chemistry & Chemical Biology 
John A. Paulson School of Engineering and Applied Sciences (SEAS) 
Email: jaiz@seas.harvard.edu 
Website: https://aizenberglab.seas.harvard.edu/ 

Description of the project: A water droplet deposited on slippery liquid-infused porous surfaces (SLIPS) forms an axisymmetric annular wetting ridge near its base by collecting lubricant oil from its vicinity. Due to unbalanced surface tension forces, such droplets exhibit remarkable mobility when this symmetry breaks. In this work (both experimental and modeling), we rationalize the characteristic merging velocity and force of interaction between two water droplets on SLIPS. 

Prior research experience is not required. Interest and motivation suffice to succeed on the project. 

Learning outcome: High speed imaging, image and data analysis, designing and carrying out experiments, modeling of droplet-droplet interaction, technical writing, presentation 

Number of hours the student is expected to work: Negotiable 

Mentor: Solomon Adera (postdoc, email: sadera@seas.harvard.edu

Does laboratory provide any funds to pay student’s stipend?  No. However, research funds are available through HCRP/PRISE and other fellowships (for more info email Anna Babakhanyan at ababakhanyan@fas.harvard.edu). The student can also register for a research course credit. Help is available to help the student write proposal for fellowship application. 

If interested in the position, email Solomon Adera (sadera@seas.harvard.edu

 

 

Posted Jan 30, 2018

Undergraduate research opportunity, Dr. Balskus Laboraotry

PI name: Prof. Emily Balskus, Dept. of Chemistry and Chemical Biology
Contact information: balskus@chemistry.harvard.edu; wsandoval@fas.harvard.edu

Location: 12 Oxford St, M303-H, Cambridge, MA 02138
Lab website: https://www.microbialchemist.com/

Description of the project and duties: Our gut is colonized by trillions of microorganisms, thereby exerting a profound effect on our health. This project seeks to find small molecules that interfere with gut microbial metabolic pathways that are prevalent in the human body may be connected to disease. The identified compound(s) will serve as tools for studying the role of these pathways in the gut microbiota and may also be starting points for the development of therapeutics. To find these compounds, we will employ phenotypic high-throughput screening (HTS) of diverse small molecule libraries from the Institute of Cell and Chemical Biology (ICCB) at Harvard Medical School. The duties of the student will be focused on testing and optimizing assay conditions for high-throughput screening. These assays will use bacterial growth, or other phenotypes, as reporters for activity. We seek motivated students wanting to learn more about the fascinating roles of the human gut microbiota and the use of chemistry as a tool for studying this complex microbial community.   

Skills required: Basic microbiology and/or biochemistry skills are required.
Learning outcome: Microbiology lab skills including high-throughput screening techniques. Research skills involving study design and data analysis, including growth kinetics and analysis of data from high-throughput screens. Statistical tools for HTS experiments. Presentations and scientific writing skills.
Number of hours students are expected to work: 40 hours at least per week for summer, and 10 to 15 h / week during the semester.
Mentoring: Dr. Walter Sandoval, a postdoc in the lab, will mentor and will work closely with the student on a daily basis. The student will also have access to mentoring from Prof. Balskus and other group members.
Does laboratory provide any funds to pay student’s stipend: The lab does not provide any stipend; therefore, students are encouraged to apply to the HCRP and other fellowships (PRISE, Microbial Sciences Initiative) or register for a research course credit (see your concentration advisor).

Interested applicants, please send your resume to Prof. Emily Balskus (balskus@chemistry.harvard.edu) or Dr. Walter Sandoval (wsandoval@fas.harvard.edu)

 

 

Posted Jan 4, 2018

 

Center for Depression, Anxiety and Stress Researc, Dr. Pizzagalli Lab

Center for Depression, Anxiety, and Stress Research, McLean Hospital / Harvard Medical School

The Center for Depression, Anxiety and Stress Research (CDASR; Director: Diego A. Pizzagalli, Ph.D.) was launched in 2010 at McLean Hospital - the largest psychiatric facility of Harvard Medical School. Using an interdisciplinary approach, CDASR investigators are working to identify the biological, environmental, and psychological factors that contribute to depression and anxiety. The ultimate goal of this research is to develop better prevention and treatment strategies for these prevalent disorders.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required. Volunteers assist lab members utilizing various methodologies (e.g., brain imaging, electrophysiology, clinical interviews) to study emotional and cognitive processing in both healthy and psychiatric populations, primarily major depression. Both undergraduate students and recent college graduates are eligible. 

To apply contact: Dr. Diego Pizzagalli, dap@mclean.harvard.edu
115 Mill Street, Belmont, MA 02478
http://cdasr.mclean.harvard.edu/

 

 

Uncovering novel etiologies for male infertility, Dr. Morton Lab

Program in Genetics and Genomics and Certificate Program in Leder Human Biology and Translational Medicine, Biological and Biomedical Sciences Program, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA   Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA  Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, USA

Unexplained infertility affects 2-3% of reproductive aged couples. One approach to identifying genes involved in infertility is to study subjects with a clinical phenotype accompanied by a de novo balanced chromosomal aberration (BCA) through the Developmental Genome Anatomy Project (DGAP). DGAP230 has oligospermia and 46,XY,t(20;22)(q13.3;q11.2). While BCAs may reduce fertility by production of unbalanced gametes, a chromosomal rearrangement may also disrupt or dysregulate genes important in fertility. After refining the location of chromosomal breakpoints, a qPCR walk across genes in the topologically associated domains (TADs) at the sites of rearrangement revealed exclusive dysregulation of SYCP2, which resides 1.5 Mb away from the der(20) breakpoint. We found that this misexpression derives from a single allele and developed a novel technique to determine that the expressed allele resides in cis with the der(20) breakpoint. 4C-Seq was used to identify putative enhancers from chr22 that may be responsible for the misexpression. SYCP2 encodes synaptonemal complex protein 2, a member of the synaptonemal complex (SC) involved in homologous chromosome synapsis in meiosis I. We hypothesize that SYCP2 misexpression may impair proper spermatogenesis by meiotic nondisjunction. To mode

Number of hours/week: Negotiable: depends on arrangement
Requirements: Knowledge of genetics and bioinformatics would be helpful.
To apply contact: Dr. Cynthia Morton, cmorton@bwh.harvard.edu
New Research Building room NRB160 77 Avenue Louis Pasteur Boston, MA 02155

http://mortonlab.bwh.harvard.edu

 

 

100 Million years of Fish in the Sea, Dr. Sibert Lab

Department of Organismic and Evolutionary Biology & Department of Earth and Planetary Sciences

Fishes are the most diverse group of vertebrates on the planet, and are found in nearly all modern aquatic ecosystems, including oceans, lakes, and rivers. In my lab, we use a combination of biological and geological tools to study how fish, and their roles in these ecosystems have change through time. We use microfossil fish teeth and shark scales preserved in deep-sea sediments, to study changes in fish abundance, community structure, and morphological diversity, with a focus on intervals of extreme global change, including mass extinctions, global warming, global cooling, and anoxia. Current projects include:  1. Using microCT technology to study modern fish tooth, skull, and jaw morphology, to better understand the relationship between fish diet and morphology.  2. Studying the response of marine ecosystems to the Cretaceous-Paleogene Mass Extinction 65 million years ago.  3. A comprehensive study of shark taxonomy through the past 85 million years.  4. An in-depth study of how fishing pressure over the past 500 years has changed fish populations in the North Atlantic Ocean.  5. A project of the relationship between fish abundance and the evolution of diatoms, krill, and whales in the Antarctic.  We are excited about applying these tools other time periods as well.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required, and students with any level of experience are encouraged to apply. Labwork may include considerable time using a reflected light microscope, as well as heavy use of in-house computer programs. Programming experience in Python and/or R is a plus but not a requirement.
To apply contact: Dr. Elizabeth Sibert, esibert@fas.harvard.edu
26 Oxford Street Room 52, Cambridge, MA 02138
elizabethsibert.com

 

Regulation of cholesterol metabolism in diabetes, Dr. Biddinger Lab

Department of Medicine/Division of Endocrinology, Boston Children's Hospital Harvard Biological and Biomedical Sciences Program, Harvard Medical School

Individuals with type 1 diabetes are prone to hypercholesterolemia that can lead to cardiovascular disease. Here, we used Liver Insulin Receptor Knockout (LIRKO) mice to dissect some of the molecular mechanisms underlying these pro-atherogenic changes in cholesterol metabolism in a mouse model of hepatic insulin deficiency. We find that insulin deficiency reprograms whole body cholesterol metabolism by shifting the bile acid ratio towards cholic acid and its derivatives in a FoxO1-dependent manner. Cholic acid promotes cholesterol absorption from the intestine, indirectly regulating hepatic and intestinal gene expression, and driving hyperlipidemia. Thus, the increase in biliary cholic acid, increase in intestinal cholesterol absorption, suppression of cholesterologenic genes, and hypercholesterolemia that we observed in LIRKO mice was normalized by hepatic deletion of FoxO1. Similar effects were observed by knocking down the enzyme required for cholic acid synthesis, Cyp8b1, in LIRKO mice. These studies identify cholic acid as key mediator of insulin’s effects on cholesterol metabolism, and suggest that CYP8B1 may represent a novel target for the treatment of hypercholesterolemia in diabetic patients.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required, although some prior research experience in PCR or Western blotting is desired.
To apply contact: Dr. Sudha Biddinger, Sudha.Biddinger@childrens.harvard.edu
3 Blackfan Cir, Room 16030.8 Boston, MA 02115
www.biddingerlab.org

 

 

Phage Therapy Testing Against Enteric Pathogens, Dr. Faherty Lab

Pediatric Gastroenterology and Nutrition, Harvard Medical School, Massachusetts General Hospital

Shigella flexneri is a Gram-negative, facultative intracellular pathogen that invades the colonic epithelium causing diarrheal disease in children. Shigella bypasses the innate immune system and physical mucosal barrier to invade colonic epithelium. A single phage particle can target a specific bacterium species or a subset of the same species. We proposed to evaluate the ability of engineered pathogen-specific phages to target pathogenic bacteria while preserving commensal organisms in a human-derived organoid infection model. These phages will specifically identify pathogenic strains and deliver sequence-specific antimicrobials to kill of strains that meet our pathogenic criteria. Current studies utilize a wild-type phage as a S. flexneri 2a-specific antibacterial agent. We demonstrated a killing effect of the phage on S. flexneri in different conditions such as culture media, HT29 cells and cecum-derived organoid monolayers. This phage does not kill commensal bacteria, as demonstrated with E. coli HS. Future work will evaluate the efficacy of engineered phages being developed for Shigella and Salmonella-specific clearance while minimizing off-target effects on the human microbiome. Application of organoid models will give insight into the pathogenesis for enteric bacteria.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required.
To apply contact: Dr. Christina Faherty, csfaherty@mgh.harvard.edu
Mucosal Immunology and Biology Research Center Building, 114 16th St. Charlestown, MA 02129-4404
http://www.massgeneral.org/mucosal-immunology/

 

Inflammation and Edema: Neuropilins Guide the Way, Dr. Bielenberg Lab, Vascular Biology Department, Boston Children's Hospital

 

Edema or tissue swelling is exacerbated during inflammation due to increased vascular permeability at the site of injury. The vascular endothelial cell (EC) border tightly regulates microvascular fluid exchange and the degree of vessel leakiness. Vascular EC express pro-permeability vascular endothelial growth factor (VEGF) receptors and neuropilin (NRP) co-receptors that mediate stimulatory and inhibitory signals. Class 3 semaphorin-3F (SEMA3F) is a ligand for the neuropilin 2 receptor and competes for binding with VEGF. We hypothesize that during inflammation, SEMA3F reduces edema by inhibiting vascular permeability. Inflammatory cutaneous reactions are induced on the ear skin of mice and ear thickness measurements are taken as a readout of tissue swelling. To determine the effect of SEMA3F depletion, ear thickness measurements are compared between SEMA3F antibody injected heterozygous Nrp2 and control mice. To assess the effect of increased systemic SEMA3F, ear thickness measurements are compared between SEMA3F adenovirus (Ad-3F) injected and control mice. We report that SEMA3F depletion leads to significantly prolonged edema and Ad-3F treated mice exhibited lower levels of swelling. Likely, SEMA3F serves as an anti-inflammatory mechanism preventing excessive edema formation.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No previous laboratory experience required. Our lab is focused on mentoring and training the next generation of scientists. However, individuals possessing a strong work ethic and passion for learning are highly desired.
To apply contact: Dr. Diane Bielenberg, diane.bielenberg@childrens.harvard.edu
Boston Children’s Hospital  1 Blackfan Circle Karp, RB12004E Boston, MA 02115
http://www.childrenshospital.org/research-and-innovation/research/resear...

 

 

The Evolved Psychology of Punishment, Dr. Krasnow Lab, Evolutionary Psychology Lab, Department of Psychology

Why do some people receive harsher sentences for the same crime? Why do some people impose tougher punishments than others, even for the same offense? We are starting a new project on the psychology of punishment, and are looking for motivated, engaged research assistants. Our lab draws on theories from evolutionary psychology and biology to explain why different people seem entitled to different types of treatment. Biological market theory suggests that more valuable cooperative partners will receive better treatment in their relationships. Therefore, we expect that cues of cooperative partner value – especially cues that were relevant in the environment of our ancestors – will predict punishment decisions. This project would be a good fit for students who are interested in evolutionary psychology, social psychology, criminal justice or public policy, and no specific pre-existing skills are required.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required.
To apply contact: Dr. Max Krasnow, krasnow@fas.harvard.edu
William James Hall 984 https://projects.iq.harvard.edu/epl

 

 

Astrocytic Serine Racemase Expression in AD, Dr. Balu Lab, Psychiatry, Harvard Medical School, McLean Hospital

N-methyl-D-aspartate receptors (NMDARs) play a central role in synapse formation, synaptic plasticity, and learning and memory. A distinctive feature of NMDAR activation, is that in addition to glutamate, it requires the simultaneous binding of a co-agonist (D-serine or glycine). D-serine is at least as, if not more important than glycine at modulating NMDARs in the forebrain. The neuronal enzyme serine racemase (SR) synthesizes D-serine in the brain. However, SR and D-serine can be induced in reactive astrocytes following traumatic brain injury. We hypothesized that SR might also be expressed in reactive astrocytes in Alzheimer’s disease (AD). Thus, we examined post-mortem brain tissue from human subjects and from a transgenic rat (TgF344-AD) model. Subjects with advanced AD had massive astrogliosis, with these reactive astrocytes highly expressing SR. In contrast, subjects with low Braak stages had minimal astrogliosis, with SR being expressed in neurons, but not in quiescent astrocytes. Aged TgF344-AD rats showed the same pattern of SR expression as human AD tissue. Our findings have important implications for AD and other diseases associated with SR-expressing reactive astrocytes and highlight this pathway as a potential a therapeutic target to block NMDAR excitoxicity.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Having worked in a basic science lab a plus.
To apply contact: Dr. Darrick  Balu, dbalu@mclean.harvard.edu
115 Mill St. Belmont, MA 02478
http://www.mcleanhospital.org/biography/darrick-balu

 

 

Advancing coil design in micromagnetic stimulation, Dr. Bonmassar Lab, AA. Martinos Center Department of Radiology Harvard Medical School Massachusetts General Hospital

Micromagnetic stimulation (uMS) has several advantages over electrical stimulation. First, uMS does not require charge-balanced stimulation waveforms as in electrical stimulation. In uMS, neither sinks nor sources are present when a current is induced by the time-varying magnetic field, thus mMS does not suffer from charge buildup as can occur with electrical stimulation.  Second, magnetic stimulation via µMS is capable of activating neurons with specific axonal orientations.  Moreover, as the probes can be completely insulated from the brain tissue, we expect to significantly reduce the problem of excessive power deposition into the tissue during magnetic resonance imaging (MRI). uMS technology was first developed in our laboratory and is entirely based on commercial components off the shelf, which are readily available to researchers. However, commercial inductors are designed to maximize efficiency (Q-factor), which consists in trapping the generated magnetic field to minimize its losses. Furthermore, they do not allow for multiple coil design in small and complex 3D geometries as it is often needed in neuroscience applications.We will show uMS coils developments based on a new thin-film technology at the Center for Nanoscale Systems (CNS) Harvard University.

Requirements: The research is entirely performed at the Center for Nanoscale Systems (CNS), which requires training to gain access. More information on CNS can be found on the website: https://cns1.rc.fas.harvard.edu/. The skills that will be acquired by the students after completing the training and after performing research work are similar to the ones needed to manufacture MEMS. Students interested in this type of research and working at CNS are invited to contact us to learn the various options offered.

To apply contact: Dr. Giorgio Bonmassar, giorgio.bonmassar@mgh.harvard.edu
AbiLab Building 75, Third Ave Charlestown, MA 02129 Tel. (617) 726-0962 Fax (617) 726-7422
http://www.nmr.mgh.harvard.edu/abilab/

 

 

A microRNA mediates resistance to EGFR inhibition, Dr. Slack Lab

HMS Initiative for RNA Medicine, Department of Pathology, Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Despite the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy in non-small cell lung cancer (NSCLC), all patients will ultimately develop progressive disease. Intratumor cellular heterogeneity contributes to drug resistance in many types of cancer, including NSCLC. Oncogenesis might be mediated by certain microRNAs. However, the signaling events that link cancer stemness-related microRNA to EGFR-TKIs resistance remain to be charted. We have established a new 3D organoid model for normal and malignant EGFR mutant lung cells. Resistant EGFR mutations lead to higher induced levels of microRNA-21 (miR-21) compared with that of sensitive EGFR mutations. Knocking down miR-21 inhibits tumor growth and potentiates the therapeutic efficiency of EGFR-TKIs in EGFR-mutant lung cancer cells. Conversely, overexpression of miR-21 enhances the resistance of sensitive cancer cells to EGFR-TKIs. Further RNA sequencing analysis showed that PI3K-AKT signaling pathway is associated with miR-21-mediated EGFR-TKIs resistance. Administration of locked nucleic acids against miR-21 showed synergistic effects with EGFR TKIs in overcoming resistance to EGFR-TKIs in lung cancers. MiR-21 might be a promising target in overcoming EGFR-TKIs resistance.

Requirements: No prior research experience is required.
To apply contact: Dr. Frank Slack, fslack@bidmc.harvard.edu
330 BROOKLINE AVENUE, CLS417, Boston MA 02215
http://www.bidmc.org/Research/Departments/Pathology/Laboratories/Frank-S...

 

 

The Biddinger Lab: Hunting for the metabolic path

Dr. Biddinger Lab, Boston Children's Hospital Harvard Medical School Broad Institute

Our mission is to improve the lives of patients with diabetes.   As a lab, we are working to discover the pathways and metabolites that underlie the development of diabetes-associated diseases, like atherosclerosis.  We are fascinated by metabolism, and curious about the many metabolic derangements caused by diabetes. We strive to think creatively and critically, ask important questions, and uphold the highest experimental standards.  We use whatever approaches are necessary to answer our questions--integrating biochemical, molecular, cellular, proteomic and mouse genetic approaches with clinical studies in humans. We expect that our work will ultimately enable the development of better therapies for our obese and diabetic patients.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Basic skills in molecular biology are appreciated but not required
To apply contact: Dr. Sudha Biddinger, sudha.biddinger@childrens.harvard.edu
16th Floor Center for Life Sciences Building 3 Blackfan Circle Boston, MA
www.biddingerlab.org

 

Histone deacetylases HDAC4/HDAC5 participate in os, Dr. Wein Lab, Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Background: Osteocytes are the primary mechanosensors in bone. Loading-induced bone formation requires SOST down-regulation. The intracellular signaling pathways through which loading suppresses SOST suppression are unknown. HDAC4 and HDAC5 control SOST expression in osteocytes, and are required for PTH-induced SOST regulation. The goal of this study was to determine if class IIa HDACs participate in mechanical loading induced osteocyte mechanotransduction.   Methods: 20-week-old wild type, HDAC4 conditional, HDAC5 knockout, and double knockout female mice were subjected to in vivo cantilever bending of the right tibia. Each mouse underwent a 3 wk regimen, and dynamic histomorphometry was performed on the tibia mid-shaft.  Ocy454 cells were subjected to fluid flow stress.   Results: In vivo loading studies showed that HDAC4 and HDAC5 are required for loading-induced periosteal bone formation. In WT mice, periosteal bone formation rate (p.BFR) significantly increased in response to loading. In contrast, DKO mice failed to increase periosteal BFR in response to loading. In Ocy454 cells, FFSS led to time-dependent reductions in HDAC4 S246 and HDAC5 S259 phosphorylation, with peak reductions at 90 minutes. Control Ocy454 cells showed 77.4±4.9% SOST down-regulation in response to FFSS.

Number of hours/week: Negotiable: depends on arrangement
Requirements: It is preferable to have Western blotting and qPCR skills but required.
To apply contact: Dr. Marc Wein, MNWEIN@mgh.harvard.edu
50 Blossom Street, Thier Building / Boston MA, 02114 
https://scholar.harvard.edu/wein

 

Dark matter in the human brain dopamine neurons, Dr. Scherzer Lab, Neurogenomics Laboratory and Parkinson Personalized Medicine  Brigham and Women's Hospital

Enhancers function as DNA logic gates and may control specialized functions of billions of neurons. Here we show a tailored program of noncoding genome elements active in situ in physiologically unique dopamine neurons of the human brain. 71,022 noncoding elements were transcribed many of which consistent with active enhancers, and with regulatory mechanisms in zebrafish and mouse brains. Genetic variants associated with sleep, schizophrenia, and addiction were dramatically enriched in these elements. Expression Quantitative Trait Locus analysis revealed that Parkinson’s disease-associated variants on chromosome 17q21 cis-regulate the expression of an enhancer RNA in dopamine neurons. This study shows that enhancers in dopamine neurons link genetic variation to neuropsychiatric traits.

Number of hours/week: Negotiable: depends on arrangement
Requirements: no prior research experience is required
To apply contact: Dr. Clemens Scherzer, cscherzer@rics.bwh.harvard.edu
60 Fenwood Road, 9002EE Boston, MA 02115
http://www.scherzerlaboratory.org

 

Understanding the role of antioxidants in cancer, Dr. Brugge Lab, Department of Cell Biology

Tumors face numerous demands; to meet these needs, they rewire metabolic pathways, including those that produce antioxidant cofactors. The specific role of antioxidants within a tumor cell remains poorly understood. Here, we examined the dependency of tumors on glutathione (GSH), the most abundant antioxidant in the cell. To understand whether inhibition of GSH synthesis rendered cancer cells vulnerable to targeted inhibition of oncogenic pathways, we developed a high-throughput drug sensitivity assay and interrogated the impact more than 500 compounds upon GSH depletion. Blocking GSH synthesis sensitized cancer cells to inhibition of deubiquitinating enzymes (DUBs), which when combined led to an induction of ER and proteotoxic stress and significant cytotoxicity. These findings demonstrate a crucial role of GSH in the regulation of protein homeostasis. Furthermore, our study elucidates a novel vulnerability in cancers cells that potentially can be exploited for a therapeutic benefit. 

Number of hours/week: Freshmen and Sophomores are recommended to work 6-10 hrs/week
Requirements: No prior research experience is required.
To apply contact: Dr. Joan Brugge, joan_brugge@hms.harvard.edu
240 Longwood Ave
https://brugge.med.harvard.edu/

 

Targeting lipid synthesis in malignant brain tumor, Dr. Badr Lab, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School

Glioblastoma (GBM) is the most malignant form of primary brain tumors with high mortality. The presence of stem-like GBM cells (Glioma stem cells; GSCs) within the tumor further complicates treatment by promoting therapeutic resistance and tumor recurrence. Identifying essential nutrients that fuel brain tumor growth and blocking key metabolic pathways in GBM, could offer new therapeutic opportunities to treat this fatal disease.  We present evidence that the activity of Stearoyl CoA Desaturase 1 (SCD1), an enzyme that converts saturated fatty acids (FA) to unsaturated FA is essential for maintaining the survival of highly aggressive GSCs. We show that GSCs express high levels of SCD1 compared to the normal brain, and present an increased vulnerability to SCD1 inhibition. We identified CAY10566 as a highly potent small-molecule inhibitor of SCD1. Mice treated with CAY10566 showed reduced tumor growth along with a significant increase in overall survival. Palmitic Acid, a saturated FA, increased tumor growth in a mouse model further supporting the notion that lipid synthesis promote growth of GBM.  This shows how saturated FA could fuel tumor growth and provide the preclinical evidence of the therapeutic benefit of SCD1 inhibitors to treat brain tumors in patients.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Preferable but not required.
To apply contact: Dr. Christian Badr, badr.christian@mgh.harvard.edu
Building 149, 13th Street, Charlestown, MA 02129, United States
http://www.massgeneral.org/neurology/research/researchlab.aspx?id=1739&d...

 

 

White Matter Injury in Premature Infants, Dr. Rosenberg Lab, Department of Neurology Program in Neuroscience F.M. Kirby Neurobiology Center Harvard Medical School Boston Children's Hospital

White matter injury in premature infants leads to substantial motor and cognitive deficits in survivors.  Despite improvements in neonatal intensive care, the prevalence of these neurological deficits is not decreasing and there are no targeted interventions available for the infants at greatest risk.  Our laboratory has been studying developing oligodendrocytes (the cells that ultimately produce myelin/white matter) in an attempt to better understand why these cells are particularly vulnerable to injury.  With a clearer understanding of injury pathways, we hope to develop targeted interventions for this debilitating and costly disorder.  We use a variety of in vitro and in vivo approaches in mice/rats that combine techniques such as immunocytochemistry, immunoprecipitation, immunoblotting, quantitative PCR, shRNA, behavioral assays, and zinc imaging among others.   Students would have an opportunity to work closely in the laboratory with Dr. Elitt (a neonatal neurologist/neurobiologist) and be supervised by Dr. Rosenberg (a neurologist/neurobiologist).  Particular emphasis is placed on developing realistic projects for students that mesh well with our overall research program in white matter injury.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No research experience is required.
To apply contact: Dr. Paul Rosenberg, paul.rosenberg@childrens.harvard.edu
Center for Life Sciences, 13th Floor
http://www.childrenshospital.org/researchers/paul-rosenberg

 

 

Anesthesia & Critical Periods of Brain Development, Dr. Berde Lab

Division of Pain Medicine Department of Anesthesiology, Perioperative & Pain Medicine Boston Children's Hospital.

Each year in the USA, &gt;6 million children require general anesthesia or sedation for surgical and medical procedures.  Many children also require the prolonged use of sedatives to tolerate a ventilator during intensive care.  Evidence from young animals and human infants suggest that prolonged anesthesia/sedative drug exposure may be associated with later deficits in language comprehension.  We aim to understand how early life exposure to anesthesia shapes brain development.  We use non-invasive brain monitoring techniques (EEG, NIRS), behavioral and physiological measures, in combination with advanced signal processing to investigate peripheral and central nervous system function.  Our work has shown that neurophysiologic responses to anesthetic drugs change as a function of age, particularly in the first year of life.  Ongoing work is aimed at 1) confirming what extent brain activity is shaped by the timing of age and duration of anesthesia exposure, and 2) developing therapeutic strategies to mitigate the risk of adverse neurodevelopmental outcome. Currently, available research projects involve characterizing anesthesia-induced brain activity in infants undergoing esophageal atresia treatment and who require multiple anesthetic exposures during the first few months of life.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Requirements: - No prior research experience is required - Strong organisational, written and oral skills  Desirable:  - Experience in signal processing (i.e. MATLAB) - Early morning flexibility (i.e. availability for data collection in operating rooms  from 6.30am, when relevant)
To apply contact: All positions have been filled for summer 2018. Check back in the fall for updates.
Pain Treatment Service (EN311.1) Boston Children's Hospital 300 Longwood Avenue Boston MA02115
http://www.childrenshospital.org/research-and-innovation/research/labs/b...

 

 

Translational Molecular Imaging, Dr. Caravan Lab, Martinos Center for Biomedical Imaging Department of Radiology, Massachusetts General Hospital Harvard Medical School

 

Our lab develops molecular imaging probes that allow us to visualize biochemical events in the living body using MRI, PET, and optical imaging. Projects range from new probe design through human applications. We are a multidisciplinary lab of chemists, biologists, physicists, engineers, and clinicians. We collaborate with groups at Harvard, MGH, and MIT to apply molecular imaging to problems in cardiovascular disease, liver fibrosis, kidney injury, pulmonary diseases, cancer, and neuroscience. 

Requirements: Our lab develops molecular imaging probes that allow us to visualize biochemical events in the living body using MRI, PET, and optical imaging. Projects range from new probe design through human applications. We are a multidisciplinary lab of chemists, biologists, physicists, engineers, and clinicians. We collaborate with groups at Harvard, MGH, and MIT to apply molecular imaging to problems in cardiovascular disease, liver fibrosis, kidney injury, pulmonary diseases, cancer, and neuroscience 

To apply contact: Dr. Peter Caravan, caravan@nmr.mgh.harvard.edu
75 3rd Avenue, Charlestown caravanlabmgh.weebly.com

 

Sensing with quantum defects in diamond, Dr. Park Lab, Dept. of Chemistry and Chemical Biology, Dept. of Physics

Quantum defects in diamond are used as nanoscale sensors to measure biological and chemical structures and processes in situ. In our lab, we are working with nitrogen-vacancy centers in two modalities: 1) as single addressable spins for magnetic resonance spectroscopy and imaging of single molecules, and 2) as optically-readable charge detectors for real-time imaging of neuron action potentials and frictional electrification.  Our work spans the disciplines of quantum optics, physical chemistry, nano materials and devices, surface science and biological imaging. Several projects are available depending on interest, and will involve experiment design, device/material fabrication and characterization, followed by electrical and fluorescence measurements.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: Ability to work independently while communicating effectively with the team. Prior laboratory experience is helpful, but not required - the desire to learn is more important.
To apply contact: Dr. Hongkun Park, hongkun_park@harvard.edu
Conant 041 https://hongkunparklab.com/

 

Blood vessel defects in human disease, Dr. Bischoff Lab, Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School

Our lab studies how endothelial cells (EC) – the cells that line all blood vessels and the heart - become altered in disease.  1) Infantile hemangioma (IH) is a vascular tumor that grows dramatically during infancy.  We identified an IH vascular stem cell that recapitulates key features of IH when implanted into mice.  We are focused on finding somatic mutations that drive hemangioma and hope such mutations will shed light on fundamentals of vasculogenesis and angiogenesis.  2) A somatic activating mutation in GNAQ (encodes Gα-q) was identified in Sturge Weber syndrome, a neurocutaneous disorder associated with capillary malformations on the face and the leptomeninges of the brain.  We showed the mutation is enriched in ECs, pinpointing the cell type from which the disease originates.  We are studying 1) signaling in Gα-q mutant ECs, 2) specific proteins found upregulated in mutant ECs and 3) if and how the mutant ECs fail to interact correctly with surrounding cells.  3) We study what happens to the mitral valve after myocardial infarction (MI).  We found increased endothelial- to-mesenchymal transition (EndMT) in the mitral valve after MI is associated with increased thickness, which leads to mitral regurgitation.We are looking for drugs prevent excessive EndMT post-MI.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Some previous laboratory experience with techniques such as western blots, PCR, immunostaining is highly desirable.
To apply contact: Dr. Joyce Bischoff, joyce.bischoff@childrens.harvard.edu
Karp 12th floor, Karp Family Research Building, 1 Blackfan Circle, Boston Children's Hospital, Boston, MA 02115
http://www.childrenshospital.org/research-and-innovation/research/labs/b...

 

Olfactory ensheathing cells for glioblastoma gene, Dr. Tannous Lab

Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School

Glioblastoma (GBM) is the most malignant form of primary brain tumors with a poor survival rate within 5 years after diagnosis. Standard-of-care therapy consists in a combination of radiation, chemotherapy, and maximal surgical resection of the tumor; however, these treatments have shown not been effective. The olfactory ensheathing cells (OECs) is a glial cell type that enwraps the axons of olfactory receptor neurons (ORNs) as they grow from the olfactory mucosa (OM) into the olfactory bulb. The unique ability of mammalian OM in continuously replacing its ORNs by physiological turnover and following injury is attributed to the presence of the permissive OEC environment. OECs release diffusible factors to attract neural progenitors and regulate their proliferation and differentiation. Owing to their strong ability to myelinate and guide axonal outgrowth, interact with astrocytes, as well as their immuno/inflammation-modulator and phagocytic properties, OECs therapeutic potential have been evaluated for neuronal regenerative medicine but were never studied in the context of cancer. We hypothesize that upon intranasal administration, OECs will migrate to the glioma site and deliver therapeutic transgene to tumor cells in a GBM model in vivo.  

Number of hours/week: Negotiable: depends on arrangement
To apply contact: Dr. Bakhos Tannous, bakhos_tannous@hms.harvard.edu
149 13th Street, room 6309 Charlestown, MA.

 

 

Non-coding RNAs, RNPs & Translation in Cancer, Dr. Vasudevan Lab

Department of Medicine, Harvard Medical School, MGH Center for Cancer Research, MGH Center for Regenerative Medicine & Harvard Stem Cell Institute, Harvard University

Quiescent (G0) cancer cells are dormant, reversibly-arrested cells, including stem cells, which resist clinical therapy that eliminates proliferating cancer cells. Upon chemotherapy removal, G0 cells sense the loss of their proliferating neighbors and restart cell division, restoring the cancer as recurrence. G0 shows a switch to a distinct gene expression program where RNA regulation enables persistence of this critical state. mRNA control elements and regulatory RNAs such as non-coding RNAs and microRNAs, interact with RNA binding proteins to form RNA-protein complexes (RNPs) and direct expression of clinically relevant genes; their deregulation leads to a range of clinical effects such as tumor resistance, immune and developmental disorders. The primary goal of our research program is to investigate non-coding RNA- and RNA binding protein-controlled expression of critical genes in tumors, which lead to resistance and tumor expansion. A second focus is to characterize the mechanism of expression or translation of critical genes in G0 states in cancers, stem cells and germ cells. A third aim is to develop therapeutic approaches to modulate RNA-controlled expression in tumor resistance. These investigations will provide insight and novel therapeutics on non-coding RNAs in tumors.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior experience is required in our supportive lab with dedicated and friendly students, postdocs, and lab manager. Enthusiasm for science, learning and discovery is needed.
To apply contact: Dr. Shobha Vasudevan, vasudevan.shobha@mgh.harvard.edu
MGH, Main Campus, Simches Research Bldg, 185 Cambridge St, CPZN 4100, Boston, MA 02114. Ph: 617-643-3143
http://dms.hms.harvard.edu/BBS/fac/Vasudevan.php

 

Dr. Puria Lab, Department of Otolaryngology, Harvard Medical School Speech and Hearing Bioscience and Technology, Harvard University Graduate School of Arts and Sciences  Eaton-Peabody Laboratory, Massachusetts Eye and Ear

Project 1. Cochlear Amplification: Mouse Finite-Element Model

Our knowledge of cochlear mechanics is currently undergoing a revolution. While the basilar membrane (BM) has long been considered the principal structure in cochlear motion, new techniques such as optical coherence tomography (OCT) have instead revealed not only that the reticular lamina (RL) moves in a different pattern from the BM, but surprisingly it moves 3–10 times more at low input sound levels. Additionally, RL motion is closer to the inner-hair-cell stereocilia bundle, making it more relevant than BM motion for triggering the auditory nerve. We constructed a 3D finite-element model for the mouse cochlea and tested the model against recent non-invasive OCT vibrometry measurements. The model contains, a viscous-fluid environment, the key elements of organ of Corti (OoC) cytoarchitecture sandwiched between the BM and RL, including the piezo-like outer hair cell attahed to a Deiter’s cell and it’s Phalangeal process in a Y-shaped arrangement. The model allows clear relationships to be established between cochlear amplification and the structure and material composition of the OoC. The calculations demonstrate the high efficiency of the natural OoC cytoarchitecture and imply that the particular form of the Y-shaped combination is important for cochlear amplification. This improves our understanding of the various mechanical stages of hearing and deafness. [Work supported by NIH grant R01 DC 07910.]

 

Project 2. Cochlea imaging with optical coherence tomography

Recent developments in Optical Coherence Tomography (OCT) allow measurements of cochlear motions through the bony cochlear wall without holes at spatial resolutions approaching about 10 um. We present measurements made with a commercial OCT system driven by custom software (VibOCT) that facilitates parallel-processing-based near real-time processing of measured whole A-line data to different frequency response measurements.  The 905-nm center wavelength Super Luminescent Diode (SLD) and high-speed (100 kHz) camera provide higher axial resolution (3 um in air) and temporal resolution than previous studies and a sub-nanometer noise floor in air. We gathered anatomical images of the gerbil cochlear apex in-vivo at higher resolution than available previously, sufficient to resolve individual outer hair cells, pillar cells, tunnel of Corti and inner sulcus regions.  Images from the 3rd apical turn show a bulging of Reissners membrane in-vivo that flattened post-mortem with a concomitant reduction in the distance between the Henson cell border and the stria vascularis wall. Vibrometry of the organ of Corti shows a low-pass characteristic in-vivo and post-mortem with a traveling wave-like phase delay similar to a recent study rather than the sharp tuning seen more basally. This system can provide valuable information on cochlear function, which is also useful for the development of detailed cochlear models of the passive and active gerbil apex.

 

Project 3. Drive mechanisms to cochlear hair cell stereocilia

It has been long believed that inner hair cell (IHC) stimulation can be gleaned from the classic shear motion between the reticular lamina (RL) and tectorial membrane (TM). The present study explores this and other IHC stimulation mechanisms using a finite-element-model representation of an organ of Corti (OoC) cross section with fluid-structure interaction. A 3-D model of a cross section of the OoC including soft tissue and the fluid in the sub-tectorial space, tunnel of Corti and above the TM was formulated based on anatomical measurements from the gerbil apical turn. The outer hair cells (OHCs), Deiter’s cells and their phalangeal processes are represented as Y-shaped building-block elements. Each of the IHC and OHC bundles is represented by a single sterocilium. Linearized Navier-Stokes equations coupled with linear-elastic equations discretized with tetrahedral elements are solved in the frequency domain. We evaluated the dynamic changes in the OoC motion including sub-tectorial gap dimensions for 0.1 to 10 kHz input frequencies. Calculations show the classic ter-Kuile motion but more importantly they show that the gap-height changes which produce oscillatory radial flow in the subtectorial space. Phase changes in the stereocilia across OHC rows and the IHC are also observed.

To apply contact: Dr. Sunil Puria, sunil_puria@meei.harvard.edu
Mass Eye and Ear 243 Charles Street Boston, MA 02114-3002

 

MRI/MRS in Neonates with Hypoxic Ischemic Injury, Dr. Ratai Lab

 

Department of Radiology / Massachusetts General Hospital  A. A. Martinos Center for Biomedical Imaging Harvard Medical School

We are looking for Harvard undergraduate students in Life Sciences who are interested in conducting research related to Neuroimaging. The focus of this research study will be on pediatric brain disorders.  Hypoxia-ischemic injury (HII) continues to be a major cause of perinatal mortality and morbidity. Because the prognosis for any given baby is uncertain, reliable prognostic indicators are needed. One of the most informative imaging tools to potentially influence therapy and predict outcomes is MRI. However, the value of conventional MRI appears to be limited. Magnetic resonance spectroscopy (MRS) has emerged as one of the key technique in the assessment of such injury. MRS is a promising imaging technique that enables investigators to determine the concentration of specific metabolites. Thus, the purpose of this study is to evaluate MRI/MRS for prediction of outcome in neonates after HII. The candidate will work under direct supervision of Dr. Ratai (Clinical Spectroscopist at MGH). Furthermore, the candidate will work directly with radiologists, neurologists and neuroscientists. This work will provide the candidate with research experience in neuroimaging, may lead to a conference abstract and papers, and will aid in her/his future career as neuroscientist or physician.

Requirements: No prior research experience is required.
To apply contact: Dr. Eva-Marai Ratai, eratai@mgh.harvard.edu
Building 149, 13th Street, Room 2301 Charlestown, MA 02129 http://www.martinos.org/

 

 

Demystifying cardiomyocyte maturation: a bottlenec, Dr. Pu Lab, Department of Cardiology, Boston Children's Hospital, Harvard Medical School

Recent technical advances have allowed derivation of cardiomyocytes from pluripotent stem cells or non-myocytes, providing unprecedented opportunities to model and repair injured hearts. However, these derived cardiomyocytes exhibit immature phenotypes that limit their applications. To overcome this major roadblock in cardiac regenerative medicine, we aim to understanding the principles governing cardiomyocyte maturation and to ultimately use these findings to establish novel strategies to produce mature cardiomyocytes from non-myocytes.       We recently circumvented many of technical problems that limited cardiomyocyte maturation studies establishing adeno-associated virus (AAV)-mediated CRISPR/Cas9-based somatic mutagenesis (CASAAV), a platform to quickly generate loss-of-function mutations in mouse cardiomyocytes. The technique quickly generates genetic mosaics that facilitate discovery of cell-autonomous gene function, avoiding confounding effects of heart dysfunction.      Undergraduate students are encouraged to choose from two research directions. 1) CASAAV-based genetic screen for addition maturation factors. 2) Mechanistic analysis of a recently identified maturation factor. We endeavor to provide undergraduate students a most rewarding experience.

Requirements: We accept students with and without laboratory skills. However, we will expect a longer-term commitment from inexperienced students, and prefer that these students will also commit to continuing their research during the summer.

To apply contact: Dr. William Pu, wpu@pulab.org
Enders Research Building, 300 Longwood Ave, Boston, MA, 02115 www.pulab.org

 

Comparing neuroplasticity in individuals with cere, Dr. Merabet and Bauer Lab, Laboratory for Visual Neuroplasticity Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School

Title: Comparing neuroplasticity in individuals with cerebral versus ocular visual impairment   The Laboratory for Visual Neuroplasticity studies how the brain adapts to blindness and visual impairment. Major research focuses include brain imaging technologies and virtual reality to investigate structural and functional neuroplasticity. We study individuals with cerebral/cortical vision impairment (CVI) as well as individuals with ocular vision impairment (OVI) and profound blindness. Our current research includes using  high-spatial resolution diffusion magnetic resonance imaging to trace white matter visual pathways in the brain; behavioral tests of cognitive spatial processing and visual complexity using real-world virtual reality simulations combined with eye-tracking and hand-tracking; and functional magnetic resonance imaging (fMRI) to examine brain activation related to sensory information processing. 

Number of hours/week: Negotiable: depends on arrangement
Requirements: Required:  Computer programming experience: ability to understand, to do basic debugging, and/or execute batch scripts. Knowledge of any of the following languages is a plus: Python, bash, Java, C#, matlab, tcsh, and R.   Critical thinking skills  Good to have, but not required: Interest and/or education in psychology or neuroscience  General understanding of basic statistical methods   Interest working with individuals with disabilities  Not Required: Prior research experience
To apply contact: Dr. Lotfi and Corinna Merabet and Bauer, lotfi_merabet@meei.harvard.edu
20 Staniford Street, Boston, MA, 02114 https://scholar.harvard.edu/merabetlab

 

3D-printed liquid-infused tympanostomy tubes, Dr. Lewis Lab, John A. Paulson School of Engineering and Applied Sciences, Harvard University

Tympanostomy tubes, or ear tubes, are the most common solution to relieve the symptoms of otitis media (OM), or middle ear infection, in the U.S. Most commercial ear tubes are made from silicone or fluoroplastic. While about one million ear tubes are implanted annually, approximately 7% to 37% of them fail due to occlusion caused by the adhesion of mucus, keratinocytes, or bacterial biofilms. Utilizing three-dimensional (3D) printing techniques, and a surface modification technique termed slippery, liquid-infused, porous surface (SLIPS), this project aims to create ear tubes that will prevent occlusion by cells and biofilms while enabling improved fluid flow compared to that through commercial tubes.  

Number of hours/week: Negotiable: depends on arrangement
Requirements: Wet chemistry lab skills are preferred
To apply contact: Dr. Jennifer Lewis, jalewis@seas.harvard.edu
58 Oxford St, Cambridge, MA
https://aizenberglab.seas.harvard.edu/, https://lewisgroup.seas.harvard.edu/

 

Pathogenesis of Burkholderia dolosa, Dr. Priebe Lab, Division of Critical Care Medicine of the Department of Anesthesiology, Perioperative and Pain Medicine at Boston Children’s Hospital

The Priebe laboratory investigates virulence mechanisms of bacterial pathogens, including Pseudomonas aeruginosa, members of the Burkholderia cepacia complex (BCC), Stenotrophomonas maltophilia, and Mycobacterium abscessus, with the long-term goal of developing vaccines and novel therapies. These pathogens cause serious infections among hospitalized and immunocompromised patients and in people with cystic fibrosis. Techniques used in the lab span multiple fields, including microbiology, molecular biology, genomics, cellular and molecular immunology, and animal models of infection.  Areas of focus include identifying and characterizing bacterial genes, using genomic data, that are under selective pressure during infection. Using this approach, we are studying the function of regulators of virulence and the effects of mutations in these pathways.  One of these projects includes studying bacterial genomic diversity in bloodstream infections in hospitalized children.  Another major area involves vaccine development for Pseudomonas aeruginosa infections, focusing on bacterial proteins that stimulate a Th17 response.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: No prior research experience is required.
To apply contact: Dr. Gregory Priebe, gregory.priebe@childrens.harvard.edu
Enders 424 300 Longwood Ave Boston, MA 02115
http://www.childrenshospital.org/research-and-innovation/research/labs/p...

 

 

Stem cell based targeted therapies for cancer, Dr. Shah Lab, Center for Stem Cell Therapeutics and Imaging,  Brigham and Women's Hospital, Harvard Medical School

The recognition that different stem cell types can home to tumors following transplantation has unveiled new possibilities for their use in cancer therapy. Our research is based on simultaneously targeting cell death and proliferation pathways in tumor cells in an effort to eradicate both primary and metastatic tumors in the brain using engineered stem cells. We have engineered different cell surface receptor targeted adult stem cells to release (i) pro-apoptotic proteins to specifically induce apoptosis in tumor cells; (ii) anti-proliferative nanobodies (ENb) to inhibit tumor cell proliferation; (iii) immunomodulatory proteins to enhance T cell function; (iv) anti-angiogenic proteins to target blood vessels supplying the tumor; (v) oncolytic viruses to induce viral oncolysis; and demonstrated the therapeutic efficacy of these engineered stem cells both in vitro and in vivo. We employ fluorescence/bioluminescence imaging markers and optical imaging techniques to track the fate of stem cells and tumor cells in real time in vivo. In an effort to translate these therapeutics into clinical settings, we have developed and utilized immuno-deficient and -competent mouse tumor models that mimic clinical settings of primary tumors and their secondary micro-invasive deposits in the brain.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: Applicants are expected to have experience in one or more of the following techniques: stem cell biology, oncology, gene cloning, viral vector construction and/or animal surgeries. Interns are expected to commit to 15-hours/week during academic terms and apply for full-time summer internship. They will receive training in various scientific areas including but not limited to experimental design, conduct, data interpretation and analysis, writing scientific reports and manuscripts.
To apply contact: Dr. Khalid  Shah, kshah@bwh.harvard.edu
60 Fenwood Rd. Boston, MA 02115 http://csti.bwh.harvard.edu

 

 

Discovering new treatments for metastatic cancer u, Dr. Culhane Lab, Biostatistics and Computational Biology, Dana-Farber Cancer Institute Biostatistics, Harvard TH Chan School of Public Health

Using bioinformatics, machine learning and statistics, we mathematically model the molecular pathways that drive cancer development, progression and drug resistance.  We have several exciting projects for students.   For mathematicians and computer engineers, please help us develop deep-learning and Bayesian tensor matrix decomposition algorithms to integrate multiple sources cloud-based and in-house genetics and genomics data.    Bioinformaticians, statisticians and data scientists, you will work closely with our clinical and bench biology collaborators, to develop and validate computational models of the immune microenvironment in treatment resistant metastatic cancer. In-house data includes mRNA seq, scRNAseq, DNA sequencing (mutation, CNV), microRNA, methylation, CRISPR, etc. Your analysis may discover the next generation of immune therapeutics. We have active projects in kidney, breast and ovarian cancer.    Our lab is a strong advocate for reproducible research, Bioconductor and R.  Dr. Culhane is a member of the Bioconductor Technical advisory board and a founding member of the Boston R/Bioconductor for genomics meetup group.    Pre-Med students can gain valuable experience in precision medicine, next generation sequencing and 'omics bigData analysis.

Requirements: No prior research experience is required. We are happy to teach R/Bioconductor programming to motivated students.  Please indicate in your application if you have prior experience in R, Bioconductor, Matlab, Python, C++, Java, or another programming language.
To apply contact: Dr. Aedin Culhane, aedin@jimmy.harvard.edu
Smith SM822C 450 Brookline Ave Dana-Farber Cancer Institute
https://www.hsph.harvard.edu/aedin-culhane/

 

Baron and Gori Laboratory, Dr. Baron Lab, Division of Bone and Mineral Research Dept or Oral Medicine, Infection and Immunity Harvard School of Dental Medicine

The longstanding interest of our laboratory is to understand the molecular, cellular and genetic basis of skeletal homeostasis and its regulation in health and disease.  Our current projects can be subdivided into the following areas:  1) Wnt signaling and bone. WNT signaling is one of the most important developmental signaling pathways that control cell fate decisions and tissue homeostasis. Ongoing studies on the role of WNT signaling antagonists and agonists in skeletal homeostasis are part of the current focus of the lab.   2) Hippo signaling in skeletal homeostasis and responses to mechanical loading. The Hippo/YAP-TAZ signaling, involved in various mechanical cues with implications for cell fate, tissue development and homeostasis, has been recently implicated in bone biology. Ongoing studies focus on the role of this signaling in skeletal homeostasis.   3) Mechanisms by which PTH/PTHrP regulates skeletal homeostasis. Ongoing studies focus on the exploration of novel molecular pathways by which PTH regulates MSC fate decision and favors bone formation while repressing marrow adipogenesis.   4) Osteocytes and skeletal homeostasis. Osteocytes, the most abundant cells in bone, are embedded into bone and in intimate contact with the bone matrix. Ongoing studies explore the link between the matrix that surrounds the osteocytes and the way in which they regulate bone remodeling and/or mineral metabolism.   5) Central regulation of energy homeostasis and bone formation. Ongoing studies are focused to identify the precise neuronal circuits and the cellular and molecular pathways, regulating energy homeostasis and bone formation. These studies address an important clinical challenge for aging related metabolic disorders (obesity, diabetes mellitus type 2 and osteoporosis).  

Number of hours/week: Negotiable: depends on arrangement
Requirements: Research experience in cell and molecular biology is a plus but it is not required.
To apply contact: Dr. Roland Baron, Roland_Baron@hsdm.harvard.edu
188 Longwood Avenue, Boston

 

 

Design of Tool for Analysis of Speech Development, Dr. Shattuck-Hufnagel Lab, MIT EECS Speech Communication Lab

Non-word repetition tasks have been used to diagnose children with various developmental difficulties with phonology, but these productions have not been phonetically analyzed to reveal the nature of the modi cations produced by children diagnosed with SLI, autism spectrum disorder or dyslexia compared to those produced by typically-developing children. In this thesis, we compared the modi cation of predicted acoustic cues to distinctive features of manner, place and voicing for just under 30 children (ages 5-12), for the CN-Rep word inventory, in an extension of the earlier analysis in Levy et al. 2014. Feature cues, including abrupt acoustic landmarks (Stevens 2002) and other acoustic feature cues, were hand-labeled and analysis of factors that may influence feature cue modi cations included position in the word, position in the syllable, word length measured in syllables, lexical stress, and manner type. Results suggest specific patterns of modi cation in specific contexts for specific clinical populations. These findings set the foundation for understanding how phonetic variation in speech arises in both typical and clinical populations, and for using this knowledge to develop tools to aid in more accurate and insightful diagnosis as well as improved intervention methods.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience required
To apply contact: Dr. Stefanie Shattuck-Hufnagel, sshuf@mit.edu
50 Vassar St., Rm 36-523,, Cambridge, MA, 02139
http://www.rle.mit.edu/people/directory/shattuck-hufnagel/

 

Complement is required for optic regeneration, Dr. Benowitz Lab, Harvard Medical School, Harvard Program in Neuroscience

The failure of axons to regenerate in the mature central nervous system (CNS) underlies the permanent functional deficit observed after clinical CNS damage such as spinal cord injury, traumatic brain injury, and optic nerve injury, as well as diseases such as Alzheimer’s and glaucoma. Several recent, promising strategies for improving CNS axon regrowth have been discovered using the optic nerve crush model, including inflammatory zymosan, the growth factor oncomodulin, PTEN deletion, combinatorial treatments, and chelation of free zinc using TPEN. The inflammatory response to optic nerve crush, similar to other CNS injuries and diseases, involves the complement cascade, which normally functions in response to pathogen threat by recruiting inflammatory cells, marking pathogens for removal, and directly initiating cell lysis. While the role for complement proteins and their receptors in inflammatory host defense to pathogens is well characterized, recent findings have also suggested various non-traditional roles for complement proteins in CNS development, injury, and disease, including myelin clearance, neuroprotection, neurotoxicity, neuronal migration, synaptic engulfment, and axon guidance. However, the potential involvement of complement in axon regeneration after optic nerve injury has not been investigated. We report that genetic removal of complement proteins C1q or C3 or complement receptor CR3 blocked treatment-induced RGC axon regeneration following optic nerve injury in mice. The number of GAP43-labeled, regenerating axons beyond the crush site following treatment with zymosan plus cAMP, AAV2-shPTEN plus oncomodulin plus cAMP, or TPEN was significantly reduced in several lines of complement knockout mice in comparison to wild-type littermates 14 days post-injury. However, neither C1q, C3, nor CR3 knockout consistently affected RGC survival. These data suggest that the complement system is required for axon growth in the mature central nervous system, adding to the mounting evidence for non-traditional roles for inflammatory complement proteins in the nervous system. *We are seeking a motivated, interested and detail-oriented student to join this ongoing research project*

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required
To apply contact: Dr. Larry Benowitz, larry.benowitz@childrens.harvard.edu
Center for Life Science, Room #13030 3 Blackfan Circle, Boston, MA 02115

 

 

Comparative assessment of RGC subtypes, Dr. Baranov Lab, Harvard Medical School, Ophthalmology, Schepens Eye Research Institute

Cell transplantation has been explored as a potential strategy to replace retinal ganglion cells (RGCs) lost in glaucoma and other optic neuropathies. One of the challenges in cell replacement is the availability of functional RGCs in sufficient quantity. While current protocols allow to recapitulate retinal development by forming organoids from induced pluripotent stem cells (iPSC), RGC yield remains low and the abundance of specific RGC subtypes is unknown. To address this gap, the proposed student project will be focused around three main objectives. First, a comparison of the abundance of RGC subtypes found in iPSC-derived organoids with RGC subtypes known from mouse retinas, using immunohistochemistry, qPCR and Flow Cytometry. Our data obtained for photosensitive and direction-selective RGCs points towards an underrepresentation of those RGC subtypes in iPSC-derived organoids, posing the question if modifications to the current culture protocol are needed. Hence, the second focus of the project will be to explore different approaches for the improvement of subtype specific RGC differentiation in iPSC-derived organoids, by addition of cofactors or modification of culture vessels.  Following the generation of RGCs in-vitro, their survival within the host retina after transplantation is a key objective of cell replacement. Though studies of subtype specific RGC survival following optic nerve crush indicate differential susceptibility to damage, it is unknown whether specific RGC subtypes have the same propensity to survive and integrate following transplantation. Therefore, the final objective of the project is to explore RGC subtype diversity within donor RGC populations, following transplantation. 

Number of hours/week: Negotiable: depends on arrangement
Requirements: no prior research experience required if at least 15hrs/week are dedicated - project scope within the 3 proposed parts is flexible according to students interest and availability - project suitable for 2 students looking to work together
To apply contact: Dr. Petr Baranov, Petr_Baranov@meei.harvard.edu
Schepens Eye Research Institute 20 Staniford Street Boston, MA 02114

 

 

Differential Effects of Melodic Intonation Therapy, Dr. Zipse Lab, Cognitive Neuroscience Group (CNG), Department of Communication Sciences and Disorders, School of Health and Rehabilitation Sciences, MGH Institute of Health Professions

Melodic Intonation Therapy (MIT) is a treatment for nonfluent aphasia that was first described over 40 years ago. More recently, there has been conflicting evidence as to whether the rhythmic elements, the melodic elements, or both are important in order for the therapy to be most effective. There has even been a suggestion that the tapping component of the treatment may impede progress for some people, and some people with aphasia perform extremely poorly on tasks requiring rhythm processing. This raises the possibility that the tapping element of MIT may not be beneficial for those individuals with aphasia who struggle with rhythm. The aim of this study was to investigate this question. Three participants with chronic nonfluent aphasia were included in this study, which used a single-subject design to compare standard MIT with tapping (Standard; MIT-S) to a version without tapping (No Tapping; MIT-NT). Participants’ rhythm processing and beat entrainment abilities were evaluated prior to treatment. The participants exhibited different profiles of rhythm processing ability. Treatments were administered sequentially, with the order counter-balanced across participants, for a total of 10 weeks of treatment. Results indicate that tapping is not a beneficial element of MIT for all people with nonfluent aphasia, and that rhythm processing abilities may be an important consideration. In particular, individuals who struggle with rhythm tasks in a naturalistic, musical context may not benefit from tapping.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Our lab group works on an array of clinically relevant projects and uses a variety of techniques (ERPs, behavioral methods, eye tracking, clinical assessment). Training is provided and no specific laboratory skills are required. Experience reading research papers and working with spreadsheets (e.g., Excel) is helpful.
To apply contact: Dr. Lauryn Zipse, lzipse@mghihp.edu
Charlestown Navy Yard, 36 1st Avenue, Boston, MA, 02129
https://www.mghihp.edu/research-research-labs/cognitive-neuroscience-group

 

Incorporating Inter-Study Heterogeneity into the T, Dr. Parmigiani Lab

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute Department of Biostatistics, Harvard T.H. Chan School of Public Health

We explore a setting where multiple sets of patient data gathered at different sites are available to train a predictor. These datasets may exhibit inter-study heterogeneity due to geography, selection criteria, or data processing decisions, among other sources of variation. As a result, the same feature and same outcome measured across studies may exhibit different associations within each study and produce different decision rules if all studies are considered separately. Oftentimes, these single-study decision rules do not replicate well externally [1]. Options for training predictors in the multi-study setting include merging all datasets together and ignoring heterogeneity; directly accounting for heterogeneity (e.g. meta-analysis); indirectly accounting for heterogeneity by ensembling predictors. In the third case, we examine the use of weighted ensembling using the cross-study performance of each predictor, as well as traditional methods such as unweighted ensembling and stacking [2]. We describe the characteristics of these different options in simulation and in a real-data setting with fifteen sets of data relating differential gene expression to survival in ovarian cancer patients. We show that each option can work well depending on the amount of inter-study heterogeneity, the choice of learning algorithm, and other data attributes.  1. Waldron, Levi, et al. "Comparative meta-analysis of prognostic gene signatures for late-stage ovarian cancer." JNCI: Journal of the National Cancer Institute 106.5 (2014). 2. Breiman, Leo. "Stacked regressions." Machine learning 24.1 (1996): 49-64.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required. An interest in statistics, machine learning, statistical computing, and mathematics is desirable. Some coding experience would be helpful.
To apply contact: Dr. Giovanni Parmigiani, gp@jimmy.harvard.edu
3 Blackfan Circle, Boston, MA 02115
http://bcb.dfci.harvard.edu/~gp/

 

 

Clinical Computational Neuroimaging Group, Dr. Wu Lab

Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital

The Clinical Computational Neuroimaging Group is a team of interdisciplinary individuals interested in both data science and clinical research. Our research activities focus on developing methods to improve the diagnosis, prognosis and management of patients with brain injury as a result of stroke, cardiac arrest or trauma. We use state-of-the-art MRI acquistion and analysis techniques and combine  imaging with clinical data via machine learning algorithms to create quantitative biomarkers that can be used to monitor disease status relative to “normal” tissue or evaluate progression or recovery. We will present some of our research areas. We use imaging to triage patients with unwitnessed acute ischemic stroke for thrombolytic therapy, offering treatment options to patients for whom currently none exist. We also develop techniques to predict tissue and clinical outcome after acute ischemic stroke and to evaluate therapeutic efficacy of novel stroke treatments. For comatose cardiac arrest patients, we apply imaging to predict long-term neurological outcome by investigating changes in post-arrest structural and functional brain connectivity. We also use algorithms to combine structural and functional MRI to evaluate the sequelae of post-concussive mild traumatic brain injury.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Experience working in Unix-based environments and programming.
To apply contact: Dr. Ona Wu, ona@nmr.mgh.harvard.edu
149 13th Street,  CNY 2301 Charlestown, MA 02129 USA http://www.martinos.org/lab/ccni

 

 

Validity of the ABO Approximation in Graphene, Dr. Heller Lab, Department of Physics Department of Chemistry and Chemical Biology

The adiabatic Born-Oppenheimer (ABO) approximation is widely used in molecular and atomic physics to simplify quantum mechanical calculations. In a molecular system with time-dependent nuclear coordinates, the electronic wavefunction can be computed in the ABO approximation by solving the time-independent Schrödinger equation at particular points for a Hamiltonian that is purely a function of the nuclear coordinates. We aim to show that this approach breaks down when calculating the time evolution of the electronic wavefunction of a finite sheet of graphene in the presence of thermal lattice vibrations.   We initially simulate a finite graphene sheet with thermal lattice vibrations, assigning nuclear coordinates that oscillate along normal modes. The Hamiltonian operator is then constructed explicitly as a sparse matrix using the nearest neighbor tight-binding approximation: the only nonzero terms in the matrix are the diagonal terms and the (i,j)-th elements for which atoms i and j are immediately adjacent in the graphene lattice. We then explore the dynamics of the graphene electronic wavefunction in the ABO approximation by explicitly solving the time-independent Schrödinger equation for multiple time points, considering only the n-th eigenstate of the Hamiltonian at each time point. Additionally, we calculate the system’s true time-evolved wavefunction by approximating a solution to the time-dependent Schrödinger equation, taking the n-th ABO eigenstate at t = 0 as the initial condition. We then determine the probability that the ABO state predicts the true time-evolved state as a function of time; low probability at certain times indicates breakdown of the ABO approximation.

To apply contact: Dr. Eric Heller, eheller@fas.harvard.edu
Mallinckrodt Laboratory, Theoretical Chemistry Division
https://www-heller.harvard.edu/

 

 

The Gut-Liver Axis: The Source of Inflammation, Dr. A. Hodin Lab, Department go General Surgery, Massachusetts General Hospital,  Harvard Medical School

Introduction:Thre mice lacking intestinal alkaline phosphatase(IAP)have an accelerated aging phenotype,we used this as a leaky gut model to understand the contribution of the portal system and gut in the inflammaging process during aging.Methods:C57/BL6 WT or IAP-KO mice of different ages(3-22months)were used for the aging model.Primary mouse macrophages were incubated with portal or systemic serum from different aged mice.Results:We found an age-dependent increase in inflammatory cytokine in livers of WTs(p&lt;0.05for TNF-α andp&lt;0.001forIL-6).IAP-deficient mice showed higher cytokine levels in their liver compared to their WT littermates(mRNA-fold change:TNF-α:2.23,p&lt;0.05and3.89 for IL-6,p&lt;0.01).LPS in portal and systemic serum increased as a function of age,but were&gt;1000-times higher in portal compared to systemic serum,(p&lt;0.001).Absence of IAP was associated with significantly more LPS in both portal and systemic blood.In young mice,LPS was higher in KO vs WT mice,2.32-fold systemically and1.32-fold portally.Similar trend was seen in old mice,where systemically ratios increase by 3.33 and portally1.86 fold.Upon incubation of target cells,we found that both systemic and portal serum from old animals induced significantly higher inflammation than serum derived from young animals(2.89and2.73-fold increase,respectively,p&lt;0.01and&lt;0.05).There was a highly significant difference between the magnitude of TNF-α expression induced by portal compared to systemic serum(4.06and6.02 fold increase in young and old group,respectively.p&lt;0.01).Portal serum from IAP KO mice resulted in a more pronounced inflammatory response than serum from their WT counterparts(1.89-and3.44-fold increase in young and old group,respectively.p&lt;0.001).Conclusion:Targeting the “leaky gut” with IAP could prevent the entry of gut-derived inflammatory mediators into the portal system,thus representing a novel therapy to prevent a variety of gut-derived systemic diseases.

Requirements: Our lab is. partly working on overn gut mucosal defense and the interplay between the host and the intestinal microflora. Basic techniques such as qPCR, western blots. ELISAs are daily bench experiments! but we are more than happy to train the students if they do not have any prior research experience!
To apply contact: Dr. Richard A. Hodin, RHODIN@mgh.harvard.edu
Laboratory of Gastrointestinal Epithelial Biology, Jackson building, 8th floor, Massachusetts General Hospital
http://www.massgeneral.org/generalsurgery/research/researchlab.aspx?id=1...

 

 

Laboratory of Medical Imaging and Computations, Dr. Do Lab, Radiology Department

Laboratory of Medical Imaging and Computation (LMIC) is interested in developing algorithms to improve quality of medical care by supporting physicians to work smarter, faster and better.  Even among highly-trained radiologists, there are variations among performances and mistakes are made with increased workload from reliance on medical imaging for diagnosis and monitoring progression of a disease.  Our team has been working on projects to develop algorithms that assist radiologists in making an accurate diagnosis and improve their workflow:  1).  Hemorrhagic Stroke:  Our team is currently developing an algorithm to detect Hemorrhagic Strokes on CT scans, which could improve diagnostic accuracy and to shorten response time to a medical treatment.  2).  Bone Age Assessment algorithm is a project that helps radiologists to make assessments that are more consistent by decreasing inter-radiologist variation and more efficient by decreasing reading time.  This algorithm is currently deployed and being used in MGH Radiology department.  3).  Mammographic Cancer Detection:  Developing Deep Learning algorithms to improve diagnostic sensitivity and decrease inter-radiologist variability in the classification of breast density.  4).  Body part recognition on CT:  Recognizing and segmenting body organ helps radiologist to separate out different organs to see which organ(s) is(are) affected by the disease process.   Beyond our current projects, LMIC is working towards developing an AI optimized CXR for TB.  The development and deployment of AI optimized portable CXR will help to diagnose and treating TB in parts of the world where radiologists are scarce.  LMIC is also expanding the scope of AI research to explore new areas such as care management, care coordination, financial management, and operations.

Requirements: No research experience required.  We prefer students with prior knowledge of coding in Python or use of Tensorflow. 
To apply contact: Dr. Synho Do, SDO@mgh.harvard.edu
25 New Chardon St.  Suite 400,  Boston MA 02114 lmic.mgh.harvard.edu

 

 

Diabetic Choroidopathy with SS-OCT, Dr. Miller Lab, Department of Ophthalmology, Retina Service, Harvard Medical School, Massachusetts Eye and Ear

Purpose: To compare choroidal vascular density (CVD), choroidal thickness (CT), and choroidal vascular volume (CVV) in different stages of diabetic retinopathy eyes against controls using swept-source optical coherence tomography (SS-OCT).    Methods: Cross-sectional, prospective, multi-center study including patients with different stages of diabetic retinopathy and age-matched controls. Diabetic eyes were divided into four groupsL no diabetic retinopathy (DR), non-proliferative diabetic retinopathy (NPDR), NPDR with macular edema, and proliferative DR (PDR). All patients underwent a full ophthalmologic exam and imaging using SS-OCT. En face images of the choroidal vasculature were obtained and converted to binary images using ImageJ. CVD was calculated using as a percent area occupied by the choroidal vessels in the central macular region, as well as in posterior pole. The central macular CVV was calculated by multiplying the average CVD by macular area and CT (obtained with automated SS-OCT software). Multilevel mixed linear models were used for analyses.   Results: Compared to controls (0.31 ± 0.07), central macular CVD was significantly decreased by 9% in eyes with NPDR with macular edema (0.28 ± 0.06; ß=-0.03, p=0.02) and by 15% in PDR (0.26 ± 0.05; ß= -0.04, p=0.01). The central macular CVV was significantly decreased by 19% in eyes with PDR (0.020 mm3 ± 0.005 mm3, ß = -0.01, p=0.01) compared to controls (0.025 mm3 ± 0.01 mm3).   Conclusions: CVD and CVV are significantly reduced in more diabetic retinopathy, and increasing reductions were observed with increasing diabetic retinopathy. Additional work with CVV and CVD in diabetic eye disease. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response. 

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required
To apply contact: Dr. John B.  Miller, John_Miller@MEEI.HARVARD.EDU
12th Floor Retina Service, 243 Charles Street, Boston MA, 02114

 

 

Microbiome Response to Pesticide Exposure, Dr. Brucker Lab, The Rowland Institute at Harvard

The host microbiome plays a crucial role in physiology, behavior, nutrition, and speciation of the host. The structure of the gut microbial community is highly plastic under different diets and antibiotic treatments, and perturbation to this structure can have harmful effects on the host. However, there are no studies investigating the structure and function of gut microbes when exposed to long-term environmental stress. Using the model organism, a parasitic wasp Nasonia vitripennis, and the ecologically important pollinator, the honeybee, we investigate how the gut microbiome changes and responds when exposed to low levels of a commonly used herbicide, across multiple generations. Soil and water bacteria can metabolize the herbicide; however, it is unknown if these metabolic processes can occur in the host gut and if that will change the toxicity of the compound. We observe the differences of host physiology (toxicity, body weight, mating behavior) and the gut bacterial community through 16s amplicon sequencing, qPCR, and selective bacterial isolation between atrazine exposed and control population. Using mass spectrometry and metabolic growth assays, we determined that the gut bacterial metabolism is heritable across generations. Furthermore, by screening for microsatellite markers in exposed and control populations' host genotype, we observe congruent host genome topologies to the structure of their microbiomes' – termed phylosymbiosis. Our findings highlight the significance of the microbiomes’ function in driving resistance to environmental stress and their potential role in driving genomic selection in their host. Our work is the first case of experimental phylosymbiosis.

Number of hours/week: Negotiable: depends on arrangement
Requirements: The position is open to all years, but applicants with prior experience in a biology lab are preferred - but not required. Major in a science degree is encouraged (i.e. biology, bioengineering, chemistry).  Must be comfortable with insects (spiders, bees, wasps) and bacteria (strong odors).  Applicants must demonstrate high organizational skills and attention to details, be able to follow protocols, do some minimal calculations, and willingness to learn skills quickly and efficiently. 
To apply contact: Dr. Robert Brucker, brucker@rowland.harvard.edu
100 Edwin H. Land Blvd. Cambridge, MA 02142
http://bruckerlab.org/

 

Computational Analysis of the Brain’s White Matte, Dr. O'Donnell Lab, Harvard Medical School

Our research focuses on diffusion magnetic resonance imaging, the only method that can map the connections of the living human brain. We have three main research areas: open-source software, neurosurgical planning, and computational methods for big data studies. Our machine learning technology enables discovery of thousands of unique white matter brain connections that are found very robustly in large groups of subjects. This enables neuroscience and neuroanatomy research, as well as the automated detection of crucial fiber tracts for neurosurgical planning. Our open-source software, SlicerDMRI, is downloaded 200 times per month and used in multiple brain research studies (dmri.slicer.org). Research opportunities are at the intersection of computer science and neuroanatomy, with potential to learn about statistical analyses and neuroimaging studies, as well as to contribute to open-source software.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required. Any of the following skills will be useful: experience with the Linux terminal, Python and/or Matlab coding, and interest or experience in machine learning, analysis of data, or neuroscience.
To apply contact: Dr. Lauren O'Donnell, odonnell@bwh.harvard.edu
1249 Boylston St. Boston, Massachusetts 02215
https://scholar.harvard.edu/laurenjodonnell

 

 

Finding the equation that Nature uses: Toward mech, Dr. Moorcroft Lab, Department of Organismic and Evolutionary Biology

The Moorcroft lab combine novel observations (e.g remote sensing data) and mechanistic numerical models to understand and predict dynamics in the terrestrial biosphere. The majority of the group uses the Ecosystem Demography 2 (ED2) model, which calculates the distribution of different plants and their physical properties and processes based on meteorological drivers. This model is applied to ecosystems from Arctic tundra to Mediterranean ecosystems in California to lowland rainforests in the Amazon. Students interested in joining this lab should have a background and/or interest in math and computer science. Possible projects include: - Using a variety of remote sensing observations to characterize ecosystems. - Use mechanistic models to understand plant biodiversity and its importance on the Earth system - Other relevant projects of student design. 

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required
To apply contact: Dr. Paul Moorcroft, paul_moorcroft@harvard.edu
Suite 43, HMNH, 26 Oxford St. https://moorcroftlab.oeb.harvard.edu/

 

 

Commensal-induced inflammasome activation, Dr. Cherayil Lab, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital

Gut commensal bacteria play important roles in inflammatory bowel disease (IBD). One of their contributions to the pathogenesis of this condition is via the activation of the inflammasome in macrophages and the consequent secretion of the pro-inflammatory cytokine IL-1β. Since the mechanism of commensal-induced inflammasome activation is not well understood, we carried out studies to characterize this process using two representative commensal bacteria, Bacteroides fragilis and Bifidobacterium longum. We showed that the induction of IL-1β secretion by both of these organisms was dependent on the NLRP3 inflammasome and on potassium efflux. However, it did not require bacterial viability or phagocytosis. In follow-up experiments, we found that the supernatant of B. fragilis was also able to induce IL-1β secretion and that this activity was inhibited by polymyxin B, suggesting a role for lipopolysaccharide and the possible involvement of the non-canonical inflammasome. We are currently investigating this possibility further. Our results will help to clarify the mechanisms that lead to IL-1β production in IBD and may suggest novel therapeutic strategies for this disease.

Requirements: Some experience with basic molecular biology techniques (RT-PCR, western blotting, etc.) would be helpful but is not essential. Must be willing to work with human bacterial pathogens (Salmonella) and with mice as needed. A minimum commitment of 8-20 hours per week for at least 2 semesters is required.
To apply contact: Dr. Bobby Cherayil, cherayil@helix.mgh.harvard.edu
Building 114, 16th Street, Charlestown Navy Yard, Boston, MA 02129
http://www.massgeneral.org/mucosal-immunology/

 

 

Characterization of frozen-thawed dopaminergic cel, Dr. Hallett Lab, Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital

There are approximately 1.5 million diagnosed cases of Parkinson’s disease (PD) in the U.S. Patients with this chronic progressive disorder present with motor symptoms characterized by tremor, bradykinesia, rigidity and postural instability. At the onset of symptoms and diagnosis ~ 70% of the midbrain DA neurons have already degenerated. L-DOPA can initially restore dopamine (DA) levels and motor function, but with time the therapeutic window becomes increasingly narrow with L-DOPA induced dyskinesia as a common side effect. Although deep-brain-stimulation (DBS) also can alleviate motor symptoms, such interventions ultimately lead to repeat procedures, limitations for patients in receiving other medical procedures and high medical costs. Cell replacement therapy has proven beneficial in clinical studies using cell preparations derived from fetal ventral midbrain. While fetal cell transplantations are not scalable for a larger patient population and require immunosuppression, induced pluripotent stem cells (iPSCs) are a promising alternative. iPSCs generated from affected PD patients can be differentiated into midbrain dopaminergic cells and used for autologous transplantation. The proof-of-concept of autologous transplantations using differentiated iPSCs has previously been shown by us in non-human primates (Hallett et al. Cell Stem Cell. 2015 Mar 5;16(3):269-74). In current pre-clinical efforts, we have generated iPSCs from human PBMCs using episomal reprogramming and xeno-free derivation conditions. The iPSCs have been differentiated into midbrain DA neurons using a xeno-free differentiation protocol and the differentiated cell preparations frozen and thawed with good viability and reliable reproducibility. The frozen-thawed cell preparations have been characterized based on cell viability and stability, cell content and reproducibility of differentiated cell batches, and in vivo functionality after xeno transplantations into rodents. These data provide strong support for the clinical translation of iPSC-derived midbrain DA neuron cell therapy.

Requirements: No prior research experience is required.
To apply contact: Dr. Penelope Hallett, phallet@mclean.harvard.edu
MRC, 115 Mill street, Belmont MA 02478 www.neuroregeneration.org

 

 

Nuclear medicine imaging instrumentation, Dr. Sabet Lab, Gordon Center for Medical Imaging, Department of Radiology, MGH

In our imaging instrumentation lab, we focus on developing high-performance and advanced radiation imaging systems by rigorously studying and addressing some of the fundamental limitations and obstacles of today’s imaging systems. One specific research area in our lab is fabrication of new category of radiation detectors using ultra short laser pulses for Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) applications. In this regard, we developed Laser-Induced Optical Barriers (LIOB) technique where a high power pulsed laser is tightly focused inside the bulk of a radiation scintillator crystal, causing a local modification of the crystal structure. The modification is manifested by a change in refractive index (RI) of the material, where the modified region (called Optical Barrier) will have a RI lower than that of the unmodified crystal. Using the LIOB technique we place a pattern of optical barriers to manipulate scintillation light spread inside the radiation detector to achieve high spatial resolution radiation detector and hence improve the medical image quality. We are now able to create novel detector designs tuned for a specific medical imaging application by optimizing the optical barrier pattern. Our ongoing projects include development of brain-dedicated PET detector system, development of prototype sub-mm spatial resolution small animal PET, design optimization of a cardiac-specific SPECT system, development of a scintillator-based photon counting CT detector, fabrication of intra-operative positron+gamma probe for surgical application, and GPU programing and machine learning for performance optimization of detectors processed by the LIOB technique.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: Other than logical thinking and enthusiasm, no other skill is required! Computer programming in MATLAB, LabVIEW, Python, etc is a plus. Students will learn all the necessary skills in the lab.
To apply contact: Dr. Hamid Sabet, hsabet@mgh.harvard.edu
149 13th Street Rm #5222
http://gordon.mgh.harvard.edu/gc/people/faculty/hamid-sabet/

 

 

Repurposing Feraheme Drug for PET/SPECT Imaging , Dr. Yuan Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School

Heat Induced Radiolabeling (HIR) of Feraheme (FH) nanoparticles (NP) is a chelator free, radiocation surface adsorption (RSA) method using heat (120°C) to bond cations to the iron oxide core of FH NP in less than 3 hours. It repurposes the FH NP from its current uses of iron anemia treatment (FDA approved indication) and MR contrast agent (off-label use) to a radiolabeled PET or SPECT agent. HIR is a three-step but a one-pot process which includes “Loading” of radioations by heating, “Striping” off the loosely bonded cations by a small chelator chelation, and a “Size-exclusion-chromatographic” purification. HIR differs from other RSA methods in its (i) radiocation flexibility by using any of three cations employed in clinical imaging (89Zr4+, 64Cu2+ and 111In3+), (ii) procedural simplicity: bonding radiocations to a NP drug with heat, (iii) leaving the physical and biological properties of FHNP drug unchanged and, (iv) ability to generate multivalency of targeting groups.  When injected, HIR-FH NPs can be internalized by circulating monocytes that traffic to normal lymph nodes and abnormal sites of inflammation. In addition, many bioactive molecules can be attached to the HIR-FH NPs and their bioactivities are well retained for receptor targeting, which grants HIR FHNPs potentials for active targeting drug delivery and cell labeling.  HIR is unique to repurpose FH into a PET/SPECT agent for imaging the monocyte arm of the immune system. Meanwhile, the surface modified HIR-FH NPs provide potential general agents for ex vivo cell labeling, in vivo PET cell tracking, and targeted radiation therapy.

Requirements: Better to have skills of HPLC and LCMS, but optional
To apply contact: Dr. Hushan  Yuan, hyuan@mgh.harvard.edu
149 13th St., Charlestown, MA 02132
http://gordon.mgh.harvard.edu/gc/people/faculty/hushan-yuan/

 

 

Driving with visual impairment, Dr. Bowers Lab, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School

Older drivers are the most rapidly increasing segment of the driving population. Continuing to drive in older age is very important to maintaining independence and a high quality of life. However, the onset of age-related vision or cognitive impairments may compromise driving safety. Currently the regulations regarding driving with impaired vision vary widely across the states and lack scientific basis. People with impaired vision can legally drive in some states but not others.  Research at Bowers Lab focuses on quantifying the effects of different types of vision impairments on driving performance using a high-fidelity driving simulator. Driving performance is evaluated by measuring steering and lane-keeping skills and the detection of hazards in a timely manner. In addition to these measures, head and eye movements are recorded to better understand scanning (i.e. looking) behaviors while driving on highways and approaching intersections in city settings.   We have ongoing studies evaluating the effects of cataracts, age-related macular degeneration, and hemianopia (the loss of half the field of vision following a stroke or traumatic brain injury) on driving performance. Our goals are to understand more about how each type of vision loss affects driving and how people with vision loss compensate for their impairment.   In another set of studies we are evaluating the effects of different kinds of distraction on timely detection of hazards in the driving simulator and how the effects of distraction differ in younger and older drivers, with and without vision impairment.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience necessary
To apply contact: Dr. Alex Bowers, alex_bowers@meei.harvard.edu
20 Staniford Street Boston, MA 02114
http://www.masseyeandear.org/research/investigators/b/bowers-alexandra-r

 

 

The Kuchroo Lab, Dr. Kuchroo Lab, Brigham & Women's Hospital Ann Romney Center for Neurologic Diseases Evergrande Center for Immunologic Diseases Harvard Medical School

We are an immunology lab that studies autoimmunity, which refers to an inappropriate immune system attack on the body’s own tissues. It underlies many devastating human diseases, such as multiple sclerosis (MS), type I diabetes, rheumatoid arthritis and colitis. In the Kuchroo lab, we study the contribution of CD4+ T cells to the development of autoimmunity. In particular, we study experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Using transgenic and knockout mice, we aim to shed light on the genes and molecular pathways that control CD4+ T cell responses in EAE. For example, the lab has identified new cell surface receptors that can lead to the death or exhaustion of autoreactive T cells. Further, we have characterized novel CD4+ T cells called the Th17 cells which induce autoimmune tissue injury.

Number of hours/week: Negotiable: depends on arrangement
Requirements: no requirements
To apply contact: Dr. Vijay Kuchroo, vkuchroo@evergrande.hms.harvard.edu
60 Fenwood Road, BTM 10022  Boston, MA 02115  
http://kuchroolab.bwh.harvard.edu/

 

 

Hijacking Host Kinases for HIV-1 Phosphorylation, Dr. Yu Lab, Ragon Institute of MGH, MIT and Harvard

As a small virus with restricted genome size, HIV-1 critically depends on host machinery to support its life cycle. Upon infecting CD4+ cells, HIV-1 integrates itself into the host genome and replicates itself, all the while interacting with host cellular components. One such interaction involves protein phosphorylation cascades which is yet to be characterized in the context of HIV-1 proteins. Phosphorylation is known to regulate protein folding, localization, activity, half-life, and interaction with other molecules. Host kinase-mediated phosphorylation thus may regulate mechanisms indispensable to viral replication and virulence. In collaboration with the Broad Institute, we have used highly-sensitive mass spectrometry-based phosphoprotein profiling approaches for proteome-wide mapping of HIV-1 phosphorylated sites in infected CD4+ T cells as well as cell-free virus. We have detected over 30 unique phosphorylated sites on HIV-1, few of which also serve as targets for immune response. This is the first study to comprehensively map global landscape of phosphorylated residues on HIV-1 proteins. We are continuing to characterize the functional impacts of these viral protein modifications such as effects on viral fitness, which in turn could be targeted by pharmacologic or immunologic interventions.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required. Must have curiosity, strong work ethics, and a sense of humor!
To apply contact: Dr. Xu Yu, xyu@mgh.harvard.edu
400 Technology Square 7th Floor Cambridge, MA 02139
http://www.ragoninstitute.org/portfolio-item/yu-lab/

 

BMP signaling in bones and joints, Dr. Rosen Lab, Developmental Biology HSDM

Research in the Rosen Lab focuses on the role of bone morphogenetic protein (BMP) signaling in the molecular and cellular processes that build the tissues and organs of the musculoskeletal system. Using the mouse as a model system, some of the questions we are currently examining are:  1. BMP signaling in joint morphogenesis: Both too much and too little BMP signaling lead to joint malformations during embryogenesis, suggesting that BMP signaling must be tightly regulated both spatially and temporally. We are studying the cellular and molecular mechanisms involved in this process.  2. BMP signaling in the regulation of bone shape and strength: The skeleton is made up of 270 bones at birth; these elements display a wide variety of sizes and shapes. BMP signaling is a primary effector of bone width through its actions on progenitor cells located in the periosteum, the outer surface of bones. As the ratio of bone length to bone width determines how strong each individual bone is, we are interested in the process by which growth in bone length is coordinated with growth in bone width to achieve optimal bone strength.  

Requirements: No prior research experience is required. Willingness to work with mice is required.
To apply contact: Dr. Vicki Rosen, Vicki_rosen@hsdm.harvard.edu
REB 510 188 Longwood Avenue Harvard Catalyst

 

Protective role of cGK1 in SMC in mouse stroke mod, Dr. Atochin Lab, Harvard Medical School, Department of Medicine, Division of Cardiology, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA

Objective: While the role of cGMP-dependent protein kinase I (cGKI) mediating cGMP signaling in vascular smooth muscle cells (SMC) is clearly known, its role as mediator/inductor of the protective effect of nitric oxide (NO) during stroke has not been completely clarified. We showed previously that cGKI has protective effect in stroke middle cerebral artery occlusion (MCAO) model in male mice. The aim of this study was to understand whether SMC cGKI has a protective role in maintaining cerebrovascular reperfusion during stroke injury in stroke MCAO model in female mice. Animals: To test specifically role of cGKI in SMC we use conditional knockout female mice which express CreERT2 recombinase under the control of smooth muscle alpha-actin (cGKI KO) after tamoxifen injection. Littermate female mice (no Cre gene) receiving the same tamoxifen treatment were used as control (cGKI WT) mice.  Methods and Results: We verify the ablation of cGKI protein expression in cerebrovascular SMC of the cGKI KO mice using a specific COOH-terminal cGKI antibody for immunohistochemistry, finding regular expression of the protein in WT mice. We develop the stroke experiments under 30 % oxygen / 70 % nitrous oxide / 1.5 % isoflurane anesthesia, using 30 minutes of MCAO filament model and 47 hours of reperfusion. By TTC brain staining we found that cGKI KO mice show greater cerebral infarct volume (89.2±11.6 mm3, Mean±SD) than cGKI WT (56±21.6) mice (n=6/group, p &lt; 0,01). The neurological deficit (5 point severity scale) was more severe in cGKI KO mice (1.3) than in cGKI WT mice (0.3).  Cerebral laser-Doppler flowmetry was utilized during MCAO to test whether regional cerebral blood flow (CBF) differences correlated with stroke outcome.  Although intraischemic CBF did not differ among groups, the CBF was greater in cGKI WT mice than in cGKI KO mice during the reperfusion (101±13 % and 75±16 % respectively (15-th minute of total reperfusion), n=6/group, p&lt; 0.01). In conclusion, this study discloses the relevance of cGKI as a protective protein regulating CBF during reperfusion and improving stroke outcome in female mice. These results suggest that cGKI and downstream pathways should be targeted in studies designed to protect brain tissue during stroke. 

Requirements: Prior research experience in molecular biology and animal physiology is preferred but not required.
To apply contact: Dr. Dmitriy Atochin, atochin@cvrc.mgh.harvard.edu
149 East, 13th street, 4 floor CVRC, MGH, Charlestown, MA 02129
http://cvrc.massgeneral.org/faculty/dmitriy-atochin-phd/

 

 

Neuropsychiatric Genetics of African Populations P, Dr. Koenen Lab, Department of Epidemiology, Harvard T.H. Chan School of Public Health

Recent advances in psychiatric genetics have identified over 100 genetic loci of associated with schizophrenia that are now being used to inform translational research. However, for historical and practical reasons, large-scale genetic studies to date have primarily used genomes with European ancestry. If this pattern continues, advances in genetics will be limited with the ensuing risk that therapeutic innovations leave out large segments of the global population. The Stanley Center for Psychiatric Research at the Broad Institute and the Harvard T.H. Chan School of Public Health are therefore undertaking to expand neuropsychiatric genetics research into Africa with the objective of improving the existing science and addressing issues of equity.  This new initiative, the Neuropsychiatric Genetics in African Populations (NeuroGAP) – Psychosis Study, aims to collect DNA and phenotypic data from more than 35,000 cases (subjects with schizophrenia and bipolar disorder) and controls from four countries in Africa: Ethiopia, Kenya, South Africa, and Uganda over the next four years.

To apply contact: Dr. Karestan Koenen, kkoenen@hsph.harvard.edu
677 Huntington Avenue, Kresge 505, Boston, MA 02115

 

 

New tech to study microbial & microbiome activity, Dr. Girguis Lab, Department of Organismic and Evolutionary Biology

Microbes are, unquestionably, the most critical members of our biosphere. They exist in every habitat, including our own bodies, playing a crucial role in mediating chemical composition and governing biogeochemcial cycles on land and in the ocean.  Notably, the last two decades have been a watershed for environmental microbiology, as major advances in gene sequencing have fundamentally changed our notions of microbial diversity, evolution, and physiological potential. However, our understanding of what microbes are doing—namely their metabolic activity and the degree to which they influence planetary biogeochemical cycles—remains in its infancy. One of the primary obstacles to furthering our understanding of microbial activity in situ is the limited number of systems available to collect co-registered geochemical and microbial data and samples.   The Girguis lab at Harvard focuses on studying microbial activity, from free-living microbes living in the deep sea to the gut microbiomes of the great whales. To that end we develop new technologies to study the metabolic activity of microbes. From underwater mass spectrometers and tunable laser diode isotope analyzers, to osmotic pumps that may soon be able to sample the chemical composition of your gut, our lab bridges the divides that often exist between science and engineering. We also starting to work closely with material scientists and bioengineers to develop new materials for use in harnessing electrical currents from microbial communities, and to develop new technologies for studying microbes in situ (within the human gut).  Currently, we are looking for engineers and engineering-minded biologists and biochemists who are interested in being a part of these efforts. We are a hard-working and fun-loving team. The students who fare best in the lab are self-motivated, open to new ideas, and willing to engage with scholars around the university and elsewhere to move the projects forward. There are also opportunities to do field work if desired, including going to sea. Undergraduate students from our lab have gone to to pursue graduate studies (e.g. Caltech, UC Berkeley, Brown University) and medical school (UC San Francisco, Univ. of Pennsylvania).

Number of hours/week: Negotiable: depends on arrangement
Requirements: The ideal candidate will be a student in mechanical or electrical engineering, computer science, or Integrative Biology. Additional experience with hardware or software, e.g. Arduino, Raspberry Pi, Solidworks, welding, machining, 3D printing). Most importantly, the person must be self-motivated and collaborative.
To apply contact: Dr. Peter  Girguis, pgirguis@oeb.harvard.edu
16 Divinity Avenue, room 3085, Cambridge MA 02138 https://girguislab.oeb.harvard.edu/

 

Early ART reduces latent HIV reservoir in infants, Dr. Lichterfeld Lab, Ragon Institute of MGH, MIT and Harvard

Background: Although antiretroviral therapy (ART) can effectively suppress HIV-1 replication and improve patient outcomes, treatment discontinuation typically results in viremic rebound due to the presence of latently-infected CD4 T cells. However, early treatment during acute infection appears to limit the establishment of this viral reservoir, possibly allowing for long-term remission. The Early Infant Treatment Study in Botswana provides a unique opportunity to examine whether immediate initiation of ART can significantly decrease proviral reservoirs in HIV-1-infected infants, which may advance the search for a functional HIV-1 cure.  Methods: Serial PBMC samples were collected from five infants with neonatal HIV-1 infection who started ART within 72 hours (n=4) or 31 days (n=1) after birth, and were followed for 84-96 weeks (w). Genomic DNA was subjected to near full-length amplification of single-genome HIV-1 templates. Resulting products were sequenced with Illumina MiSeq.   Results: Intact full-genome proviral sequences represented an average of 41% of all detected sequences at baseline, compared to 21% of detected sequences after 84/96w of ART. This corresponded to an average frequency of 76 and 3 intact sequences per million PBMCs at baseline and after 84/96w of treatment, respectively, and is consistent with a half-life of 18 weeks for intact proviral sequences during the first two years of life.   Conclusion: ART initiated very early during neonatal HIV-1 infection leads to a profound decline of intact proviral sequences in infected infants, particularly after 84/96w of treatment. Monitoring of eligible patients during future analytic treatment interruption may indicate whether long-term remission is possible.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: Some prior lab experience recommended (e.g., pipetting, sterile technique)
To apply contact: Dr. Mathias Lichterfeld, MLICHTERFELD@mgh.harvard.edu
400 Technology Square, Cambridge, MA 02139
http://www.ragoninstitute.org/portfolio-item/lichterfeld/

 

 

Host Factors Contribute to Gut Pathogen Virulence, Dr. Faherty Lab, Department of Pediatric Gastroenterology, Massachusetts General Hospital Department of Pediatrics, Harvard Medical School

Bacterial pathogens are responsible for millions of infections worldwide, with over half a million deaths annually in children under the age of five because of diarrheal disease.  Incredibly, Shigella and related enteric pathogens are vaccine-resistant bacteria whose only treatment option are antibiotics. As rates of antibiotic resistance continue to climb these pathogens become more formidable underscoring the importance of studying Shigella and related enterics.  In the Christina Faherty lab at Massachusetts General Hospital, we study gut pathogens; taking cues from human physiology to decipher specifics of some of the most challenging bacteria, Shigella.    Research in the Faherty lab is centered around Shigella transit through the gastrointestinal tract; specifically, how exposure to different digestive compounds promotes Shigella virulence, immune evasion, survival and ultimately, their pathogenic paradigm.  We currently have several ongoing projects: • Illustrating and identifying the function of bile-induced Shigella genes (a large number are unannotated or hypothetical genes!) • Identifying how Shigella binds host proteins to facilitate invasion.  • Tracing genetic changes in clinical isolates from collaborators in endemic areas. • Exploring alternative therapeutics to overcome antibiotic resistance while reducing infectious burden.  We are redefining the principles of Shigella pathogenesis using models that incorporate host physiology combined with donor derived cells while simultaneously training the next generation of scientists.  Come experience modern microbiology in an environment utilizing cutting edge techniques filled with enthusiastic researchers.  We’d love to meet you!

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience required
To apply contact: Dr. Christina Faherty, csfaherty@partners.org
114 16th Street Charlestown Navy Yard, Charlestown MA
http://www.massgeneral.org/mucosal-immunology/research/researchlab.aspx?...

 

 

Hippocampal Oxytocin Modulates Social Memory, Dr. Sahay Lab, Neurobiology, Program in Neuroscience, Harvard Medical School

The trisynaptic hippocampal pathway DG-CA2/3-CA1 plays a critical role in processing contextual information by encoding distinct representations in non-overlapping ensembles of neurons, a process known as pattern separation. Recent studies suggest a role for the dorsal CA2/3 subregion in processing social memories, raising the question of how the same hippocampal sub-regions process social information. Based on the enrichment of receptors for the social hormone oxytocin (Oxtrs) in the DG-CA2/3 axis, but not CA1, and the critical role oxytocin plays in social memory, we hypothesized that Oxtrs in dorsal DG-CA2/3 are essential for social memory processing. Here we employ pharmacological and genetic tools to demonstrate the necessity of Oxtrs in dDG and dCA2/3 for social memory, but not object memory. Further, we utilized ensemble mapping techniques to demonstrate that Oxtrs are necessary for population-based encoding of social stimuli in CA3. Optogenetic terminal-specific silencing revealed roles for distinct dCA2/3 outputs to downstream limbic regions in discrimination of objects and social stimuli. Together, these studies begin to elucidate how an evolutionarily conserved neuromodulatory hormone, oxytocin, utilizes a basic memory processing circuit in the hippocampus to modulate social behavior.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Prior research experience is key.
To apply contact: Dr. Amar Sahay, sahay.amar@mgh.harvard.edu
185 Cambridge Street CPZN-Room 4400 Boston, MA 02114 sahaylab.com

 

 

A Neural Network Basis of Brain Injury in Women , Dr. Valera Lab, Department of Psychiatry, MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, MGH/Harvard Medical School

Traumatic brain injury (TBI) in women experiencing intimate-partner violence (IPV) is common, and IPV afflicts 30 % of women worldwide. However, the neurobiology and related sequelae of these TBIs have never been systematically examined. Consequently, TBI treatments are typically absent and IPV interventions are inadequate. There has been a call for a comprehensive assessment of IPV-related TBIs and their relationship to aspects of women’s cognitive and neural functioning. In response, we examined brain-network organization associated with TBI and its cognitive effects using clinical interviews and neuropsychological measures as well as structural and functional Magnetic Resonance Imaging (fMRI) in women experiencing IPV-related TBI. We hypothesized that TBI severity would be related to poorer cognitive performance and be associated with structural and functional connectivity between cognitive networks previously implicated in other TBI populations. Severity of TBI was negatively associated with inter-network intrinsic functional connectivity indicative of TBI, between the right anterior insula and posterior cingulate cortex/precuneus (family-wise error-corrected Z &gt; 2.3, cluster- based p &lt; 0.05). This association remained significant when controlling for partner-abuse severity, age, head motion, childhood trauma and psychopathology. Additionally, intrinsic functional connectivity between the same regions correlated positively with cognitive performance on indices of memory and learning. These data provide the first mechanistic evidence of TBI and its association with cognitive functioning in women sustaining IPV-related TBI. These data underscore the need to address and consider the role TBI may be playing in the efficacy of IPV interventions ranging from emergency first responder interactions to specific treatment plans.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required
To apply contact: Dr. Dr. Eve Valera, eve_valera@hms.harvard.edu
MGH at the Navy Yard 149 13th St.  Charlestown, MA 02129
https://www.nmr.mgh.harvard.edu/lab/valera/eve-valera-phd

 

 

ER stress response and calcium homeostasis is alte, Dr. Isacson Lab, Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital

The Leucine-Rich Repeat Kinase (LRRK2) G2019S gain of function gene mutation is one of the most prevalent mutations contributing to Parkinson’s disease (PD) pathogenesis. The increased kinase activity alters mitochondrial health, axon outgrowth, intracellular trafficking and autophagy. We have previously shown that human LRRK2 G2019S iPS-derived neurons exhibit increased vulnerability to PD-associated cell stressors and modify mitochondrial dynamics, which can be rescued by LRRK2 inhibitors (Cooper et al., 2012, Sci Transl Med. 2012, 4;4(141):141ra90.). Human iPS-derived neurons carrying the LRRK2 G2019S mutation and challenged with the endoplasmic reticulum (ER) calcium (Ca2+) uptake blocker thapsigargin (THP) show a significant decrease in their ER stress responses accompanied by neurite collapse, when compared to neurons derived from healthy subject controls. As THP blocks ER Ca2+ influx via sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) and induces ER stress, this result indicates that iPS neurons carrying the LRRK2 G2019S mutation have an altered capacity to regulate Ca2+ homeostasis. Indeed, we further discovered that after THP-induced SERCA block, human iPS-derived neurons carrying the LRRK2 G2019S mutation exhibit an increase in depolarization-induced calcium influx and modified calcium decay (interpreted as buffering capacity), when compared to healthy subject control neurons. This phenotype is diminished by treatment with antisense oligonucleotides targeting the LRRK2 G2019S mutation. These data suggest that the LRRK2 G2019S mutation alters intracellular calcium homeostasis and ER stress response, potentially contributing to the PD-specific neuronal dysfunction.

Requirements: No prior research experience is required.
To apply contact: Dr. Ole Isacson, ole_isacson@hms.harvard.edu
 MRC, 115 Mill street, Belmont MA 02478
 www.neuroregeneration.org

 

 

Chi sites may reduce errors in DNA repair, Dr. Prentiss Lab, Harvard University Department of Physics

Eukaryotes are known to use complex strategies to avoid dangerous genome rearrangements resulting from double strand break (DSB) repairs that mistakenly join different copies of long repeated sequences; however, bacterial strategies have remained mysterious. In bacteria, double strand breaks repaired by the RecBCD pathway probe the sequence of double strand DNA using two ssDNA-RecA filaments with Chi site sequences on their 3′ ends. Commitment to strand exchange depends on subsequent DNA synthesis by polymerases. Our work show that though bacteria contain &gt; 5000 long repeated sequences, almost all RecA-mediated repairs can create correct products. Here we demonstrate that a combination of the dependence of DNA synthesis on the heteroduplex product at the 3′ end of a RecA filament and the sequence distributions near Chi sites can reject most incorrect DSB repair attempts. Our experimental results show that DNA synthesis is rare unless the filaments contain sequence matched heteroduplex products longer than ~20 bp. In addition, we show that the sequences adjacent to Chi sites imply that RecBCD rarely creates initiating ssDNA with long repeats at the 3′ ends and never forms a pair of initiating ssDNA from the same long repeat. Understanding the mechanisms for rejecting major rearrangements in bacterial genomes may provide better predictions of rearrangements that succeed despite this strategy, as well as new techniques for combatting bacterial infections. Finally, since insertion of two Chi sites enhances gene targeting, the additional information on the influence of mismatches in sequences adjacent to Chi sites may increase targeting efficiency.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience required
To apply contact: Dr. Mara Prentiss, prentiss@fas.harvard.edu
Lyman 222 17 Oxford Street Cambridge, MA 02138
prentiss.physics.harvard.edu

 

 

Study of immune surveillance of stem cells, Dr. Agudo Lab, Department of Cancer Immunology and Virology, Dana-Faber Cancer Institute

In order to interrogate how T cells interact with any given cell type or tissue, we recently generated the first and only green florescent protein (GFP)-specific T cell mouse called the Jedi mouse. Jedi T cells specifically recognize the immunodominant epitope of GFP presented on MHC class I, and thereby turn GFP into a model antigen. Thus, Jedi T cells can be used in combination with any of the hundreds of GFP-expressing mice or cell lines. We have used Jedi cells to dissect how T cells interact with several stem cells in their niche in vivo. There is a long-standing interest in understanding the immunogenicity of stem cells because of their role in tissue homeostasis. By transferring Jedi cells into several stem cell GFP-reporter mice, we have discovered that stem cells in the intestine, ovary and mammary gland are not protected from cellular immunity while quiescent skin and muscle stem cells are spared. Similarly, it has been shown that quiescent hematopoietic stem cells are also protected by regulatory T cells. The fact that quiescent stem cells can escape from immune attack might be the result of the necessity to avoid their clearance to ensure tissue integrity. This can help explain why mutations in long-lived stem cells would not lead to immune editing, and suggests how cancer-initiating cells may evade immune surveillance. Tissue stem cells can serve as the cancer-initiating cells of some tumors, such as in the intestine or mammary gland, and so their permissiveness to immune surveillance is relevant to preventing malignancy. Established tumors use a number of mechanisms to prevent their clearance by the immune system such as expression of PD-L1, but the events occurring at the earliest stages of tumor growth that allow them to escape are not known. Our findings suggest that cancer initiating cells might start out as immune privileged because they are quiescent stem cells. The Agudo lab‘s goal is to dissect how T cells interact with cancer initiating cells and rare disseminated tumor cells and uncover mechanisms of immune evasion in order to prevent metastasis.

Requirements: no previous lab experience is required, only curiosity and love for science!
To apply contact: Dr. Judith Agudo, judith_agudo@dfci.harvard.edu
450 Brookline Ave, Smith building, room 708

 

 

Nitric oxide limits intestinal stem cell expansion, Dr. Rask-Madsen Lab, Joslin Diabetes Center

During the last 30 years, obesity rates have doubled for adults and tripled for children in the United States.  Obesity increases the risk of several types of cancer, including colorectal cancer.  While there is a large body of literature describing how the metabolic and hormonal milieu in obesity may affect tumor progression there is very little data on whether metabolic disease affects intestinal tumor initiation. We have recently published that genetically determined insulin resistance in vascular endothelial cells promotes intestinal tumor formation in mice.  In many cases, tumor initiation takes place after an oncogenic mutation in intestinal stem cells.  Since insulin regulates endothelium-derived nitric oxide (NO) production, we examined whether NO could suppress intestinal stem cell maintenance.  In 3-dimensional culture of intestinal stem cells (organoids), the NO donors and the NO second messenger cGMP both deeply suppressed intestinal stem cell markers.  Furthermore, treatment of mice with L-NAME, an inhibitor of NO synthase, increased the population of intestinal stem cells.  We therefore hypothesize that endothelium-derived NO limit the intestinal stem cell population.  We further hypothesize that endothelial dysfunction in obesity, characterized by impaired NO production, leads to expansion of the intestinal stem cell population, thereby increasing the risk for tumor initiation.  The student project, using organoid culture and mice with genetic reporter fluorescence in intestinal stem cells, will aim to further describe how endothelium-derived NO may regulate intestinal stem cells.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Knowledge of very basic lab techniques is required; experience with cell culture is preferred.
To apply contact: Dr. Christian Rask-Madsen, christian.rask-madsen@joslin.harvard.edu
One Joslin Place, Rm 430 Boston, MA 02215
https://joslinresearch.org/investigators/Christian-Rask-Madsen

 

 

What Time Is It? Timing for Analog Seismograms, Dr. Ishii Lab, Ishii Group, Department of Earth And Planetary Sciences, Harvard University

With modern-day instruments and seismic networks timed by GPS systems, time synchronization of data streams is all but a forgone conclusion. However, during the analog era, when each station had its own clock, comparing data timing from different stations was a far more daunting prospect. Today, with recently developed methods by which analog data can be digitized, all that separates us from opening up decades worth of data is having the ability to accurately reconcile the timings of two separate stations. One among many possible and exciting applications of these digitized and timed data would be investigating changing subsurface structural features (on a volcano for example) over a much longer timescale than was previously possible. With this in mind, we introduce a new approach to time synchronization between stations based on distant earthquakes. The first arrivals of waves are identified at stations for pairs of earthquakes, one from the modern digital era and one from the analog era. These pairs are doublets that have nearly identical locations, and depths. Assuming accurate timing of the modern data, relative time corrections between a pair of stations can then be inferred for the analog data. This method for time correction depends upon the analog stations having modern equivalents, and both having sufficiently long durations of operation to allow for recording of usable teleseismic events. As a result of these requirements, this method has been developed largely with records from the Hawaii Volcano Observatory (HVO) network, which not only has a large and well-preserved collection of analog seismograms, but also has a long operating history (1912 – present) with many of the older stations having modern equivalents. The scope of this project is to calculate and apply relative time corrections to analog data from two seismic stations on the HVO network (HILB (1919 – present) and UWE (1928 – present)). Further development of this method should involve investigation of the effects of relative clock-drift, that is, the determining factor for how long a time correction is valid for, and possible ways to account for it.

Number of hours/week: Negotiable: depends on arrangement
Requirements: It is preferable for students to have some computer programming background, and the patience to work through large and complex data sets.
To apply contact: Dr. Miaki Ishii, ishii@eps.harvard.edu
20 Oxford St. Cambridge, MA 02138
http://www.seismology.harvard.edu/index.html

 

 

Immune Tolerance of Mouse Renal Allografts, Dr. Alessandrini Lab, Department of Surgery, Massachusetts General Hospital and Harvard Medical School

The kidney is pro-tolerogenic by mechanisms as yet unknown. In mice, tolerance of kidney allografts can occur spontaneously in certain strain combinations, such as DBA/2 to C57/BL6. We have previously identified novel lymphoid structures in all accepted kidney grafts that may be important in tolerance induction and named them Treg-rich lymphoid structures (TOLS). Depletion of Tregs results in the dissolution of these structures, resulting in renal allograft rejection. Nevertheless, few studies focused on the lymphoid neogenesis in allografts after organ transplant, and their role in graft tolerance or rejection is not fully understood. Here we further investigated the lymphoid characteristics and the functional properties of TOLS, and the time-course and mechanism of TOLS formation. We show that TOLS are composed of various immune cell types and as these structures form, expression of podoplanin, a protein that is a marker for lymphatics, increases within the TOLS, suggesting that these structures are developing lymphatic-like characteristics. Renal grafts showed massive peri-arterial infiltrates at week 1 and by week 6 form into TOLS. We further show that TOLS formation is dependent on the chemokine receptor, CCR7.  Renal allografts in a CCR7 KO recipient exhibit much smaller TOLS with increased fibrosis and pathological evidence of rejection. Nanostring RNA analysis shows that CCR7 and its ligand, CCL19, are highly expressed in accepted kidney allografts when compared to rejecting and native kidneys.   We conclude that TOLS are characteristic of renal allograft acceptance and their formation is dependent on the CCR7/CCL19 pathway.

Requirements: No prior research experience is required.
To apply contact: Dr. Alessandro Alessandrini, aalessandrini@partners.org
55 Fruit Street, Thier 8 Boston, MA 02114
http://www.massgeneral.org/research/researchlab.aspx?id=1624&display=pro...

 

 

Seizures in critically ill neonates and children, Dr. Sansevere Lab, Neurology  Division of Epilepsy  Boston Children's Hospital

Purpose: To describe the main clinical and electroencephalographic (EEG) characteristics of neonates and children who underwent continuous EEG (cEEG) monitoring in the neonatal and pediatric intensive care unit (ICU) while requiring extracorporeal membrane oxygenation (ECMO). Methods: Retrospective study of  patients &lt;1 month to 21 years with a cEEG  in the neonatal and pediatric intensive care unit(ICU) while requiring ECMO  at Boston Children’s Hospital from October 2010 to September 2016.  Key findings: 401 (219 children and 182 neonates) were reviewed. Of those, 179 (100 children and 79 neonates) had an EEG while on ECMO. The most common reason for ECMO was cardiac arrest due to a congenital heart defect (119/401) and respiratory distress/pulmonary hypertension (105/401). Indication for EEG monitoring included detection of subclinical seizures (176/179) and to characterize of events (25/179). The percentage of patients on ECMO with cEEG increased from 31% (16/51) in 2011 to 65% (47/72) in 2016. Seizures were detected in 17.9% of patients who had an EEG while on ECMO (32/179). Of those, 19 were neonates and 13 were children. About half of the seizures observed were electrographic only in nature (15/32).  Significance: This study adds to the current literature showing that patients on ECMO are at high risk for subclinical seizures. Additional study is needed to further characterize this group with regards to the effect of high seizure burden on overall outcome on mortality.  

Number of hours/week: Negotiable: depends on arrangement
Requirements: Role primarily includes medical record abstraction  Includes screening for the appropriate targeted patients  Provides the experience of building a database and assisting with data entry using the RedCap database  No prior research experience required Experience with REDCap is a plus
To apply contact: Dr. Arnold  Sansevere, Arnold.Sansevere@childrens.harvard.edu

 

 

GINGER, Dr. Chibnik Lab, Department of Epidemiology at the Harvard T.H. Chan School of Public Health; the Stanley Center at the Broad Institute of MIT and Harvard

The Global Initiative for Neuropsychiatric Genetics Education in Research is a research education program that aims to boost global capacity to conduct neuropsychiatric genetics research. To achieve this goal, the Harvard T.H. Chan School of Public Health and the Broad Institute of MIT and Harvard have teamed up with multiple African institutions to create a global neuropsychiatric genetics training program, which launched in July 2017.  With backing from their home institutions, 17 Research Fellows from East and South Africa have been enrolled to take part in the inaugural two-year GINGER program. The GINGER program includes three main components, specifically:  (1) Workshops: A series of neuropsychiatric epidemiology and genetics workshops focusing on epidemiology, genetics, writing, mentoring and building a research program;  (2) Virtual Coursework: Weekly virtual training and mentoring sessions to follow the progress of projects and learn from renowned researchers in the field of neuropsychiatric epidemiology and genetics;  (3) Onsite Training: Onsite skills based training to be taught at each collaborative institution, open to a larger audience, including graduate students, fellows, research assistants and project managers.  The GINGER Program offers semester and summer long internships to give interested Harvard University undergraduates the opportunity to gain experience in education program development and management, scientific curriculum development and impact evaluation and monitoring. Examples of potential projects and hands-on learning activities include:   • Program Evaluation and Impact: Work with GINGER team to develop program evaluation impact and evaluation methods including key          performance indicators; evaluation methods will be used to determine program impact and effectiveness and track this impact over time.          • Curriculum Development: Learn scientific research curriculum development processes by supporting curriculum design for international research          training workshops; gain exposure to scientific research methods through joining and supporting virtual classroom and/or workshop activities.  The GINGER Program offers a unique opportunity for students to learn about program development, program impact evaluation and monitoring, and to gain international work experience. Students will engage with GINGER stakeholders located in East and South Africa as well as the United Kingdom.     

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research or teaching experience is required.
To apply contact: Dr. Lori Chibnik, lchibnik@hsph.harvard.edu
677 Huntington Avenue Boston MA 02115
https://ginger.sph.harvard.edu/

 

 

Organ-specific contrast agents for diagnosis, Dr. Choi Lab, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School

Our research focuses on the development of novel tissue- and organ-specific contrast agents for diagnosis, staging, and treatment of human diseases. Tumor-targeted fluorophores are of particular interest, which can be used for image-guided surgery by specifically visualizing target tissue with high optical properties and avoiding nonspecific uptake in normal background tissues. During the past decade, we have been systematically probing the relationship among the hydrodynamic diameter, shape, charge, and hydrophobicity of nanoparticles and small molecule contrast agents on in vivo biodistribution and clearance (Nature Biotech. 2007, Angew Chem Int Ed. 2011, Adv Mater. 2016).  Using invisible near-infrared (NIR) fluorescence and 3D molecular modeling, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting such as lung and sentinel lymph nodes (Nature Biotech. 2010), human prostate cancers (Nature Nanotech. 2010), and human melanomas (Nature Biotech. 2013). Another project we have been working on is the targeting of endocrine glands and their tumors. We have currently achieved specific targeting on the thyroid/parathyroid glands (Nature Medicine, 2015), pancreas (Theranostics, 2014), thymus, pituitary gland (anterior/posterior separately), and adrenal glands (manuscripts in preparation/review). We have also developed other tissue-specific targeted fluorophores for lymph nodes (Theranostics, 2014), bone and cartilage (Angew Chem Int Ed. 2014), kidneys, liver, lungs, spleen, salivary glands, brown fat, seminal vesicle, and prostate (manuscripts in preparation). Regenerative medicine with tissue-engineered scaffolds is another area of interest, and we have developed biodegradable NIR scaffolds and cellular trafficking systems for longitudinal monitoring of tissue regeneration (Sci Rep. 2013 and Biomed Mater. 2013). Using dual-channel intraoperative imaging systems, we are currently trying to target cancerous tissue/vasculature/nerve (tumors), cardiovascular diseases, and bone/cartilage/inflammation (rheumatoid arthritis) simultaneously with different colors, which lay the foundation for clinical translation to image-guided surgery.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience is required.
To apply contact: Dr. Hak Soo Choi, hchoi12@mgh.harvard.edu
149 13th Street, Rm 5222, Charlestown, MA 02129
gordon.mgh.harvard.edu

 

 

Enzymatic Release of Therapeutic Peptides from Eng, Dr. Joshi Lab, The Wyss Institute for Biologically-Inspired Engineering,  Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS)

Curli fibers are the major proteinaceous component of E. coli biofilms. They are composed of repeating CsgA monomers, which are secreted from the cells and self-assemble into robust fibers. Utilizing this biofilm component, the Joshi Lab has developed the BIND platform (biofilm-integrated nanofiber display). By genetically engineering the curli operon, we have been able to append various protein domains to CsgA, combining their function with the inherent structure, robustness and self-assembly properties of curli fibers.   One potential avenue for applying the BIND platform lies in the emerging field of engineered probiotics. By implementing this approach in E. coli Nissle 1917 – a probiotic strain of E. coli – we can create engineered fibers with bioactive domains that confer therapeutic effects in the human gut. Our lab is currently pursuing this approach, fusing CsgA to proteins such as anti-inflammatory cytokines and trefoil factors (TFF) – a family of proteins that have been shown to promote epithelial restitution. Biofilm-based display is a novel approach to drug delivery. However, its potential can be further enhanced by inducing the release of the therapeutic molecule from the biofilm matrix in a controllable manner. This would introduce an additional controllable element to the system, and could increase the local dose of the therapeutic molecule in response to specific physiological stimuli. The focus of this project is to design and incorporate a cleavable linker into the BIND platform and assess its specificity and its effect on the concentration of the released peptide.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience required
To apply contact: Dr. Neel Joshi, njoshi@seas.harvard.edu
The Wyss Institute for Biologically-Inspired Engineering,  Center for Life Sciences (CLS), Room 203 3 Blackfan Cir, Boston, MA 02115 http://joshi.hms.harvard.edu/

 

 

Biology of Hematopoiesis and Cancer, Dr. Zon Lab, Stem Cell Program and Division of Hematology/Oncology at Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Harvard Stem Cell and Regenerative Biology

The Zon laboratory focuses on the developmental biology of hematopoiesis and cancer in zebrafish and mouse systems, as well as human cell lines. We have collected well over 30 mutants affecting the hematopoietic system. Some of the mutants represent excellent animal models of human disease. Recently, we identified several chromatin factors with essential roles at various stages of hematopoiesis. We have developed suppressor screening genetic methods and found that transcriptional elongation regulates blood cell fate. We also have performed chemical genetic screens to identify components implicated in blood development and have found that prostaglandins increase the number of blood stem cells. This has led to a clinical trial to improve engraftment for patients receiving cord blood transplants; phase I trials were just successfully completed.  The laboratory has also developed zebrafish models of cancer. Using transgenics, we have generated a melanoma model in the zebrafish system. Transgenic fish get nevi, and when combined with a p53 mutant fish develop melanomas. We recently found a histone methyltransferase that can accelerate melanoma, and discovered a small molecule that blocks transcription elongation and suppresses melanoma growth.

Number of hours/week: Negotiable: depends on arrangement
Requirements: Prior lab experience is recommended but not required.
To apply contact: Dr. Leonard Zon, zon@enders.tch.harvard.edu
Sherman Fairchild Biochemistry Building Ground Floor 7 Divinity Ave Cambridge, MA 02138

https://zon.tchlab.org

 

 

Motion sickness and dizziness in migraine disorder, Dr. Lewis Lab, Departments of Otolaryngology & Neurology, Harvard Medical School Jenk's Vestibular Physiology Lab, MEEI

People with migraine are more sensitive to motion as a car passenger (e.g. motion sickness) and many also experience episodic dizziness (vestibular migraine, VM). No clear mechanism has been described that explains why migraineurs develop these vestibular symptoms. Thus, we studied VM patients and control groups (normal subjects, patients with migraine but no dizziness, and patients with dizziness but no migraine) using psychophysical (perceptual thresholds) and eye movement tests during motions that simultaneously activated the semicircular canals (angular velocity sensors) and otolith organs (gravity and linear acceleration sensors).  We hypothesize that the brain's integration of these vestibular cues is abnormal in vestibular migraine patients.

Requirements: Understanding of excel and simple statistical methods.  Familiarity with matlab is desired but not required.To apply contact: Dr. Richard Lewis, richard_lewis@meei.harvard.edu
243 Charles St., Boston, MA Room 913, Jenk's Vestibular Lab, MEEI

 

 

An evolutionarily conserved role of Presenilin, Dr. Shen Lab, Program in Neuroscience, Harvard Medical School, Brigham and Women's Hospital

Title; An evolutionarily conserved role of Presenilin in neuronal protection in Drosophila brain Abstract; Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of g-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment and age-dependent neurodegeneration. The roles of Drosophila Presenilin (Psn) and Nicastrin (Nct) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality, a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct, neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80ts system caused shortened lifespan, climbing defects, increases in apoptosis and age-dependent neurodegeneration. Together, these findings demonstrate that similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain.

Requirements: Experience in the research lab, especially in fruit fly, would be recommended, but no prior research experience is also welcome.

To apply contact: Dr. Jie Shen, jshen@bwh.harvard.edu
77 Avenue Louis Pasteur, NRB Rm 636C, Boston, MA 02115
http://www.shenlab.net/HOME.html

 

 

Plasmodium falciparum protein export, Dr. Duraisingh Lab, Harvard School of Public Health, Department of Immunolgy and Infectious Disease

Malaria causes about 500,000 deaths yearly. Plasmodium falciparum accounts for the majority of severe malaria cases, drives morbidity and mortality, and consequently has exerted a strong selection pressure on the human genome. Identification of host factors important for P. falciparum growth within the red blood cell (RBC) is important for developing therapies that are less prone to resistance as opposed to drugs targeting the parasite. P. falciparum exports some of its proteins to the surface of the erythrocyte, including important virulence factors such as P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 allows infected RBCs to bind to the endothelial microvasculature and avoid spleen clearance, contributing to disease severity in malaria. Human heat shock protein 70 (HSP70) has been associated with P. falciparum protein export, however direct genetic evidence is missing since mature RBCs lack a nucleus.  Our overall goal is to identify critical host determinants for PfEMP1 export using forward and reverse genetic tools. We will use erythroid progenitor cell lines that still have a nucleus to perform genetic perturbation screens (lentivirus-based CRISPR/Cas9 forward screens) with the goal of identifying RBC proteins important for PfEMP1 export. The hits identified by the screen will be validated and characterized on their specific role in protein trafficking. We will also interrogate the specific role of host HSP70 in P. falciparum protein export using reverse genetics in erythroid progenitor cells. The findings from this work will elucidate the specific host-pathogen interactions that are pathogenic in malaria and highlight them as novel therapeutic targets.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week
Requirements: No prior research experience required. Only enthusiasm to learn.
To apply contact: Dr. Manoj  Duraisingh, mduraisi@hsph.harvard.edu
651 Huntington Avenue, FXB 203
https://sites.sph.harvard.edu/duraisingh-lab/

 

 

Nanobody–antigen conjugates elicit HPV-specific an, Dr. Ploegh Lab, Program in Cellular and Molecular Medicine, Boston Children's Hospital

High-risk human papillomavirus (hrHPV)-associated cancers express viral oncoproteins (e.g. E6 and E7) that induce and maintain malignant phenotypes. The viral origin of these proteins makes them attractive targets for therapeutic vaccine development. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APCs) can serve as targeted delivery vehicles for antigens attached to them. Indeed, antigen site-specifically conjugated via a C-terminal sortase motif on the VHH can induce a CD8+ T cell response. Here we investigated the ability of an anti-CD11b VHH (VHHCD11b) to target APCs and serve as the basis for a therapeutic vaccine against HPV+ tumors. Mice immunized with VHHCD11b conjugated to an MHC I immunodominant E7 epitope (E749-57) had more E7-specific CD8+ T cells compared to those immunized with E749-57 peptide alone. These CD8+ T cells conferred prophylactic protection against a subsequent challenge with HPV E7-expressing tumor cells. In a therapeutic setting, VHHCD11b-E749-57 vaccination resulted in greater numbers of CD8+ tumor infiltrating lymphocytes compared to mice receiving E749-57 peptide alone in HPV+ tumor-bearing mice as measured by in vivo non-invasive VHH-based immuno-positron emission tomography (immunoPET), which correlated with tumor regression and survival outcome. Together, these results demonstrate that VHHs have promise as a therapeutic cancer vaccine platform.

Number of hours/week: Negotiable: depends on arrangement
Requirements: No prior research experience required.
To apply contact: Dr. Hidde Ploegh, hidde.ploegh@childrens.harvard.edu
1 Blackfan Circle, RB 06215, Boston, MA 02115
http://www.childrenshospital.org/research-and-innovation/research/progra...

 

 

Migration in the Mediterranean, Dr. Tuross Lab, Human Evolutionary Biology, FAS, Harvard University

Through the use of light stable isotopes we are studying the movement of peoples through the Mediterranean in antiquity.  From Spain to Turkey, with a major focus in Sardinia, we are studying the flow of people across diverse environments, water regimes and diets.  The work involves the preparation of bone and tooth protein for mass spectrometry; data analysis and graphic display development.  We are a small, friendly lab and we like to travel.

Requirements: No prior research experience is  necessary, but if you have training then you can move into a higher level of complexity in the project.
To apply contact: Dr. Noreen Tuross, tuross@fas.harvard.edu
11 Divinity Ave, Cambridge MA 02138

 

 

Screening for OspB Protein Targets, Dr. Goldberg Lab, Department of Medicine, Infectious Diseases, Massachusetts General Hospital and Harvard Medical School

Shigella species infect colonic epithelial cells and cause dysentery, resulting in 80 to 165 million cases of disease and 600,000 deaths annually worldwide. In addition to a lack of vaccines for Shigella, the extremely high rates of antibiotic resistance among Shigella isolates makes it especially difficult to treat. Consequently, there is a need to understand how Shigella target host cell signaling pathways to develop an environment conducive to their survival and replication. OspB, an effector protein delivered by Shigella into epithelial cells, alters the mTOR signaling pathway, a mammalian cell pathway that promotes cell growth and proliferation. Preliminary data suggest that OspB is a protease, but little is known about the mechanisms of OspB function and or its proteolytic substrate(s). We found that when we express OspB in the yeast Saccharomyces cerevisiae, yeast growth is suppressed in the presence of rapamycin or caffeine, chemicals that activate yeast TOR. To identify a proteolytic substrate(s) or cellular pathway targeted by OspB, we conducted a screen in which we looked for yeast proteins that might be degraded as a result of OspB function. Our approach was to identify yeast genes that, when overexpressed, rescue the sensitivity of yeast cells expressing OspB to caffeine. The initial screen of the overexpression library identified several suppressors of OspB-induced caffeine sensitivity and is a promising approach to understanding the mechanisms of OspB function.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required.

To apply contact: Dr. Marcia Goldberg , marcia.goldberg@mgh.harvard.edu

65 Landsdowne Street Cambridge, MA 02139

http://www.massgeneral.org/medicine/research/researchlab.aspx?id=1714

 

 

Molecular underpinnings of Parkinson's Disease, Dr. KHURANA Lab, Ann Romney Center for Neurologic Diseases Department of Neurology Brigham and Women's Hospital Harvard Medical School   Principal Faculty Harvard Stem Cell Institute

Synucleinopathies, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), are common and devastating neurodegenerative diseases affecting millions in the United States alone. They present severe challenges to patients and caregivers, and place a growing burden on our public health system. There is currently not a single strategy to prevent, slow or reverse these diseases. Considerable attention has been given to directing therapies at aggregation of alpha-synuclein (α-syn), a small 14-kDa protein associated with phospholipids
in membranes and synaptic vesicles in the presynaptic terminals of neurons.  Our lab is focused on understanding molecular underpinnings of α-synuclein mediated neurotoxicity. Over the course of several years, we have generated invaluable models of PD, from unicellular yeast all the way to patient derived induced pluripotent cells (iPCs) that can be differentiated into neurons. We have created proteome-scale maps from the genetic and physical interactors of α-synuclein. We are currently undertaking challenging CRISPR screens of mammalian PD models to expand our knowledge not only to understand the cellular functions of α-synuclein but also to understand how disturbed protein networks around it contribute to PD.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required however basic molecular biology is a plus. The students are expected to be highly motivated and willing to show enthusiasm to learn new techniques.

To apply contact: Dr. VIKRAM KHURANA, VKHURANA@BWH.HARVARD.EDU

Building for Transformational Medicine (BTM) 10th Floor (Rm 10016L) 60 Fenwood Road  Boston MA 02115

http://khuranalab.bwh.harvard.edu/

 

 

Seismological Constraints on the Inner Core, Dr. Ishii Lab, Department of Earth and Planetary Sciences, Harvard University

The inner core, the kernel of the Earth, plays crucial role in our planet’s formation and evolution, as well as powering the Earth’s magnetic field that protects life from harmful cosmic rays. Despite its importance, it is least understood of the Earth’s interior. Its remote location (more than 5000 km below ground) and harsh environment make it impossible to send a probe, and we must rely upon information collected at the Earth’s surface. When large earthquakes occur, they cause the Earth to ring like a bell and by observing and listening to these sounds, we have determined that the inner core is solid iron, and it is surrounded by the outer core which is liquid iron. However, the liquid outer core isolates the inner core, sound-proofing certain types of sound, obscuring our understanding of the detailed structure and composition of the Earth’s inner core. We develop new methods to circumvent the obstacles posed by the Earth’s liquid outer core to hear the exotic sounds of inner-core ringing in order to better determine its structure and composition. This entails careful analyses of seismograms recorded by seismic stations throughout the world. This study will report the first observation of the exotic inner-core sounds, and these novel data will provide unprecedented constraints on the materials and structure that make up the center of our planet.  

Number of hours/week: Negotiable: depends on arrangement

Requirements: Computer programming skills and patience to work with complicated data.

To apply contact: Dr. Miaki Ishii, ishii@eps.harvard.edu

20 Oxford Street   Cambridge MA, 02138

http://www.seismology.harvard.edu/index.html

 

 

Point of Care MRI, Dr. Ackerman Lab, Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School

Point-of-Care Testing (POCT) is an emerging concept in the delivery of medical diagnostic services: rather than in the hospital or clinic, the test is performed in the physician’s office, at the bedside, in the surgical suite, in the back of the ambulance, on the battlefield, in the isolated rural village. Magnetic Resonance Imaging (MRI), one of the most resource-intensive and expensive, yet most informationally and diagnostically rich, medical tests, has been late to this game. Our laboratory is developing point-of-care MRI technology to bring down the cost and portability of high quality MRI through advances in magnet system design. Other innovations from our lab have transformed the scanner into a treatment device by enabling it to perform therapeutic interventions while also providing diagnostic information. We are seeking bright, energetic students to join our team to assist with software development, electronic engineering, materials chemistry, and in conducting experiments.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required. We are particularly interested in students with skills in software, electronics, lab bench chemistry, or crafts (machine tools, soldering, shop craft, etc.). Expect to get your hands dirty--we build stuff.

To apply contact: Dr. Jerry Ackerman, jerry@nmr.mgh.harvard.edu

Martinos Center, Room 1.031 Massachusetts General Hospital 149 13th St. Charlestown, MA 02129

 

 

Characterization of Neuropetide Profile in Gliobla, Dr. Tannous Lab, Institution: MGH Department: Neurology

Gliomas account for the great majority of primary tumors that arise within the brain parenchyma. Gliomas are classified based not only in histopathology appearance but also on molecular parameters. Glioblastoma (GBM) is the most aggressive type of gliomas. The mainstay of treatment of GBM is surgery, followed by radiation and chemotherapy. Despite this aggressive treatment, the mediam survival of patients with GBM is &lt;2 years. Recently, GBM molecular profile revealed two predominant subtypes, proneural and mesenchymal, while multiple subtypes can reside in the same tumor. GBM that presents mesenchymal signature is more aggressive and has an increased therapeutic resistance. Plasticity between these 2 subtypes is observed in tumor recurrence and therapy resistance. Neuropeptides are small protein-like molecules expressed and released by neurons to modulate their communication. Neuropeptides are involved in several biological activities, many of them may act as growth factors by stimulating cell proliferation and mitogenesis. Because the current standard GBM treatment is unlikely to result in prolonged remission, there is a great effort to better understand the oncobiology of GBM and overcome tumor resistance. Since neuropeptides play an important role in neurogenesis and neuronal communications, we hypothesized that these small molecules can also play a role in modulating neural stem-like cells and resistance in GBM. The aim of this work is to characterize the neuropeptide profile of GBM cell lines (sensitive vs resistant to chemotherapy) and patient-derived neural stem-like cells with different molecular subtypes, a subpopulation of the tumor known to be responsible for tumor initiation, recurrence and resistance. Our preliminary data show a different neuropeptide profile between sensitive vs resistant GBM cells, as well as proneural vs mesenchymal stem-like cells. These results suggest that neuropeptide may play a role in tumor resistance and plasticity.

Number of hours/week: Negotiable: depends on arrangement

To apply contact: Dr. Bakhos Tannous, bakhos_tannous@hms.harvard.edu

Neuroscience Center Molecular Neurogenetics Unit 149 13th St., room 6101 Charlestown, MA 02129

 

 

Restoration of hearing by CRISPR/Cas9, Dr. Chen Lab, Eaton-Peabody Laboratory, Department of Otolaryngology, Massachusetts Eye & Ear Infirmary, Harvard Medical School

Introduction: CRSIPR/Cas9-mediated genome editing emerged as potential new treatment due to the permanent editing results. However most CRISPR/Cas9 has been performed in germline or in vitro by viral vectors or DNA vectors, which raise long-term safety concerns. We report here hearing restoration in a PMCA2 deaf mouse model (Obl-Oblivion) by direct protein delivery and CRISPR/Cas9 mediated genome editing.Methods: gRNAs against the Pmca2 mutation were screened by in vitro endonuclease assay and by using Obl fibroblasts. Potent gRNAs were complexed with Cas9 protein by lipid formulation, which were then injected to neonatal mouse Obl inner ear. Hearing studies were performed at one, two and three months after injection, with tissues harvested for characterization.Results: Hearing recovery of 10-45dB were observed, which is specific to gRNAs against the mutation, whereas in control inner ear no recovery was detected. Genome editing led to significant improvement in outer hair cell survival, demonstrating recovery of Pmca2 function in the outer hair cells. Preservation of neurites of auditory ganglion neurons was detected by genome editing.Conclusion: Our study demonstrates high-efficiency genome editing and hearing restoration in the Obl deaf mouse model by transient in vivo inner ear delivery of Cas9 and gRNA complex. This is the first time that CRISPR/Cas9 mediated genome editing has been successfully applied to disrupt mutation and restore function in a genetic disease model by direct protein delivery in vivo. Our strategy is applicable to restoration of hearing in a wide range of genetic hearing loss models with potential for the application in human.

Requirements: There is no specific prior research experience is required.

To apply contact: Dr. Zheng-Yi Chen, zheng-yi_chen@meei.harvard.edu

243 Charls str, Boston, MA, 02114

http://www.masseyeandear.org/research/investigators/c/chen-zheng-yi

 

 

Halko Lab: Non-invasive network neuromodulation, Dr. Halko Lab, Department of Neurology

The Halko laboratory, located within the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center, investigates the role that large-scale neural networks play in cognitive performance and disease pathology.   Utilizing state-of-the-art technologies, including transcranial magnetic stimulation and functional connectivity magnetic resonance imaging, these studies probe casual relationships of networks.  We have demonstrated it is possible to modulate specific brain networks and observe functional connectivity changes across the entire brain, providing insight into how brain networks are connected, change, and are altered in disease states.  These studies are applied with a translational focus, investigating the interaction between a basic science understanding of human cognitive networks and therapeutic intervention in neurological and psychiatric disease states such as schizophrenia, bipolar disorder, ADHD, traumatic brain injury and Alzheimer’s disease. Students interested in a research or thesis opportunity, especially those with basic knowledge of UNIX, programming, statistics, and/or cognitive neuroscience, are encouraged to apply. Research training and mentoring will be provided by members of the lab, which consist of Principal Investigator Mark Halko; Dr. Simon Laganiere, Instructor of Neurology and Director of the Executive Function and Attention Disorders Clinic; Dr. Roscoe Brady, Assistant Professor of Psychiatry and Director of Psychopharmacology Education; and research collaborators at multiple institutions in the greater Boston area.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience required.

To apply contact: Dr. Mark Halko, mhalko@bidmc.harvard.edu

330 Brookline Ave, Kirstein Building KS 158, Boston, MA 02215

http://tmslab.org

 

 

Web-based Data Visualization Tools for Genomics, Dr. Gehlenborg Lab, Department of Biomedical Informatics Harvard Medical School

Our lab has developed HiGlass (http://higlass.io), an innovative and versatile approach for visualizing and interacting with genomic data on the web. HiGlass was recently featured in a Nature news story (https://tinyurl.com/ybtgvmcm) and is being utilized by a large NIH consortium as well as individual investigators to view genomics and epigenomics data as well as 3D genomic interaction data. We are currently developing a number of applications that build on the HiGlass platform and applying them to a diverse range of questions. This effort requires implementation and design of additional data visualization components, server-side data management components, and APIs, as well as curation of example data sets from the literature that demonstrate the capabilities of these tools.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: Students should have experience in at least one of the following three areas:  1. Software development with JavaScript or 2. Software development with Python or 3. Genetics/Genomics

To apply contact: Dr. Nils Gehlenborg, nils@hms.harvard.edu

10 Shattuck Street Boston, MA 02115

http://gehlenborglab.org

 

 

Finding a needle in the haystack: Detecting rare c, Dr. Yuan Lab, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute; and Department of Biostatistics, Harvard Chan School of Public Health

Rare cell types are of large importance.  While stem cells are rare in mature tissues, these cells are the building blocks from which other cells are formed, and are necessary for tissue repair and maintenance.  Or consider circulating tumor cells: found in a miniscule proportion of all blood cells, circulating tumor cells could hold the key to noninvasive cancer diagnosis and monitoring.  Unfortunately, rare cells often go unnoticed, as most common-use cell type detection methods are not designed to handle their detection.  By addressing the unique challenges associated with differentiating between noise and biological signal from these rare cell types, our lab is developing methods to find these cell types.  What other important rare cell types can we discover?

Number of hours/week: Negotiable: depends on arrangement

Requirements: Students are expected to have good programming and analytical skills.

To apply contact: Dr. Guo-Cheng Yuan, gcyuan@jimmy.harvard.edu

Longwood Center, Room 1060, 360 Longwood Ave, Boston, MA 02215

http://bcb.dfci.harvard.edu/~gcyuan/

 

 

Hippocampal Activation during Memory Retrieval, Dr. Silveri Lab, Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital/Harvard Medical School

Multiband blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data were acquired at 3T during performance of a virtual Morris Water Maze task on retrieval and motor conditions. Participants included 14 healthy alcohol and drug naïve adolescents, 13-14 old years, recruited for a three-year longitudinal MRI study. Data from the baseline visit demonstrate significant BOLD activation in the hippocampus during the retrieval condition when participants used cues in the environment to navigate to a hidden platform, compared to the motor condition, when no cues were present. In contrast, significant BOLD activation was observed in the default mode network during the motor condition, when cognitive task demands were minimal. Activation of the anterior cingulate cortex was observed when the retrieval condition was compared to a probe trial, in which navigation occurred in the retrieval environment, while unbeknownst to participants, the platform had been removed. These are the first fMRI data to be reported from an adolescent cohort using a virtual translation of this classic memory task, known to be sensitive to detecting alcohol and drug-related effects on memory performance. These preliminary findings are consistent with hippocampal and prefrontal activation patterns observed during memory retrieval in a prior adult study. Given that the age of onset of alcohol use often occurs during this crucial period of brain development, data acquired using this task at baseline, when adolescents are alcohol and drug naïve, may shed light on the role of memory in risk for early substance use.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Neuroscience or Psychology Majors preferred Interest in Neuroimaging and Psychiatry ideal No skills required

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill Street, Belmont MA 02478

http://nlamh.mclean.harvard.edu/

 

 

Evolutionary Genomics of Malaria, Dr. Neafsey Lab, Infectious Disease and Microbiome Program, Broad Institute Department of Immunology and Infectious Diseases, Harvard T.H.Chan School of Public Health

The Neafsey lab uses computational genomic tools to study the evolution of Plasmodium malaria parasites and their Anopheles mosquito vectors. We focus on topics that impact public health, including: the evolution of drug resistance, the application of natural genetic variation to vaccine design, and the use of genomic data to understand disease transmission dynamics. We are currently looking for an undergraduate student who is interested in studying the evolution of Plasmodium transmission. Plasmodium is a sexually reproducing, eukaryotic parasite that has a complex transmission cycle. The Plasmodium lifecycle involves obligate stages within mosquito, human liver, and human blood cells. At each of these life stages, Plasmodium adopts a unique cellular form capable of invading and replicating within the specific host or vector tissue. Blocking the transition from one form to the next would block parasite transmission. This project is using evolutionary genomic approaches to understand these critical life stage transitions with the aim of informing new transmission-blocking approaches. During the course of the project, the student will analyze Plasmodium genomes using a variety of approaches drawn from molecular evolution, comparative genomics, and population genetics. The project will be wholly computational and will involve both implementing genome analysis software and writing custom scripts.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior experience or skills are required. The exact project can be tailored to match the student’s past experience with and interest in coding. Students with no coding background are welcome to apply.

To apply contact: Dr. Daniel Neafsey, neafsey@broadinstitute.org
Broad Institute: 75 Ames St  Cambridge, MA 02142 HSPH: 665 Huntington Avenue  Boston, Massachusetts 02115

www.hsph.harvard.edu/daniel-neafsey/

 

 

Understanding MKRN3 mechanisms of action in the re, Dr. Kaiser Lab, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston

An elaborate neural network integrating internal and external signals governs the onset of puberty and subsequent fertility. The precise nature and components of this network are not well established, but it is clear that puberty is triggered by the central increase in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which stimulates the secretion of the pituitary gonadotropins, necessary for the activation of gonadal function. In addition to environmental factors, this process is influenced by genetic factors, many of which remain to be identified. Our group recently reported loss-of-function mutations in the makorin ring finger protein 3 (MKRN3) gene in association with central precocious puberty. While several stimulators of GnRH secretion have been identified previously, MKRN3 is the first protein to be identified that acts as an inhibitor of puberty onset. The aim of my project is to determine the role and mechanisms of action of MKRN3 in puberty onset. To this end, I will use a combination of in vivo and in vitro approaches to identify the targets of MKRN3 action and thereby unravel the neuronal network controlling puberty onset. The results of this study may lead to the generation of new therapeutic targets for the treatment of pubertal and reproductive disorders.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required.

To apply contact: Dr. Ursula Kaiser, UKaiser@bwh.harvard.edu

Department of Medicine Endocrinology, Diabetes and Hypertension 221 Longwood Avenue, EBRC Room 202 Boston, MA 02115

http://physiciandirectory.brighamandwomens.org/details/999/ursula-kaiser...

 

 

Brain Activation in College Binge Drinkers, Dr. Silveri Lab, Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital/Harvard Medical School

The transition to college is associated with increased binge drinking during a time when prefrontal cortex (PFC) and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky drinking among college freshmen. The current study used functional magnetic resonance imaging (fMRI) to record brain activity during a task that required participants to ignore background images that were positive, negative or neutral while performing an inhibitory control task (go-nogo). Subjects were 23 college freshmen (7 male, 18-20 years) who engaged in a range of drinking behavior (past three months’ binge episodes range = 0-19, mean = 4.6, total drinks consumed range = 0-104, mean = 32.0). Brain activation on inhibitory trials (nogo) was contrasted between negative and neutral, and between positive and neutral conditions. Results showed higher recent binge drinking was significantly associated with decreased activation in PFC during negative relative to neutral trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral trials. Thus, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Neuroscience or Psychology Majors preferred  Interest in Neuroimaging and Psychiatry ideal  No skills required

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill Street, Belmont MA 02478

http://nlamh.mclean.harvard.edu/

 

 

Cdkal1 predisposes to type-2 diabetes by promoting, Dr. Banks Lab, Brigham and Women's Hospital, Divisions of Endocrinology and Genetics, Harvard Medical School

Our goal is to understand the mechanisms by which genetic predisposition can contribute to developing type 2 diabetes. Unbiased approaches to link genetic loci to increased risk for people to develop T2D have identified many sites which may hold the promise for understanding and combatting this disease. However relatively few new mechanistic insights have been made into common genetic contributors to diabetes. Cdkal1 is one of the first and most powerful loci identified by GWAS and is strongly confirmed in diverse populations worldwide. Healthy individuals with disease-associated noncoding SNPs within the Cdkal1 gene have decreased first-phase insulin secretion, suggesting a role in pancreatic islets. Cdkal1-deficient mice appear to model this phenomenon well, as these animals also exhibit decreased first-phase insulin signaling. But what does Cdkal1 do? Prokaryotic homologs of Cdkal1 regulate protein translation by enzymatic modification of tRNA. Current models of Cdkal1 activity suggest this mechanism causes a specific defect in protein translation of insulin. However, we recently refuted this model with unbiased systems-based approaches. Rather, we find that CDKAL1 controls mitochondria through a novel post-translational protein modification which has not previously been observed in eukaryotes.  Our experiments will investigate the mechanisms by which Cdkal1 can alter mitochondrial function with isolated proteins, cell lines, primary cells, or mice over-expressing or deficient in Cdkal1. Together these experiments hold the promise of explaining how commonly inherited genetic factors contribute to the development of type-2 diabetes

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior experience is necessary

To apply contact: Dr. Alexander Banks, abanks@bwh.harvard.edu

77 Avenue Louis Pasteur, HIM 632

bankslab.bwh.harvard.edu

 

 

Boredom Susceptibility and Grey Matter Volume, Dr. Silveri Lab, Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital/Harvard Medical School

Developmental reductions in grey matter volume (GMV) coincident with adolescence have been associated with age-related maturation of behavioral and cognitive control. Adolescents with a family history of alcoholism (FH+) exhibit alterations in grey matter structure that may confer neurobiological vulnerability for future hazardous drinking. To date, only focal regions have been examined in FH studies of brain structure. Thus, this study examined the influence of FH status on whole-brain morphology, and associations with sensation seeking and impulsiveness, two traits known to predict hazardous drinking. Thirty-three adolescents, ages 13-14 years old, were stratified into FH+ (n=17) and FH- (n=15) groups. Participants underwent magnetic resonance imaging (MRI) at 3T and completed the Brief Sensation Seeking Scale (BSSS) and the Barratt Impulsiveness Scale (BIS). Volumetric brain data were extracted using the Freesurfer pipeline and all FH comparisons were analyzed using regression models that included age and sex as covariates, which accounted for head size. FH+ status was associated with larger total GMV (p&lt;0.03), relative to the FH- group, which appeared to be driven by larger cortical (p&lt;0.001) rather than subcortical GMV. Although behavioral measures did not differ significantly between groups, the boredom susceptibility component of sensation-seeking was positively correlated with larger cortical GMV (p&lt;0.01), only in the FH+ group. The relationship between higher GMV and susceptibility for boredom in the FH+ group suggests that FH status may moderate the trajectory of grey matter sculpting that is developmentally adaptive, which may provide one possible pathway to a predisposition for risk-taking behavior.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Neuroscience or Psychology Majors preferred.  Interest in Neuroimaging and Psychiatry ideal.  No skills required.

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill Street, Belmont MA 02478

http://nlamh.mclean.harvard.edu

 

 

Hibernating yeast cells and cancer dormancy, Dr. Motamedi Lab, MGH -Centre for Cancer Research and Department of Medicine, Harvard Medical School

The research program in the Motamedi laboratory is focused on understanding how changes in eukaryotic chromatin are made, maintained and propagated, and how these changes establish alternative cellular states particularly in response to environmental stress. Our work on mechanism of RNA- mediated heterochromatin formation in the fission yeast help establish the Nascent Transcript Model, according to which non-coding RNAs (ncRNAs) tethered to chromatin provide a platform for the assembly of RNA processing (Motamedi et al. Cell 2004) and chromatin-modifying, -binding, and -remodeling (Motamedi et al Mol Cell 2008) complexes, which spread in cis to the neighboring chromosomal regions (Li, Motamedi Mol Cell 2009). This model established the first molecular blueprint for how long (lncRNAs) and small (sRNA) noncoding RNAs cooperate to regulate chromatin states. Currently, one of the major focus in the lab is cellular quiescence (or G0) - a poorly understood cellular state, which is a major contributor to tumor dormancy and cancer resistance. Our latest work in the fission yeast (Joh et al Mol Cell 2016) has revealed a new function of heterochromatin proteins - the establishment of the transcriptional program of G0 cells. With our novel G0 discoveries, our lab is well positioned to exploit our expertise and innovative approaches to successfully carry out this work. We have the demonstrated experience in molecular biology, genetics, biochemistry, cell biology, with specific expertise in G0, RNA-mediated epigenetic gene silencing, and chromatin biology. In addition to our own expertise, we have mass spectrometric, statistics and bioinformatics support for this work.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: Basic understanding of genetics, biochemistry and cell biology. No previous lab experience is required but a basic theoretical understanding of techniques is desired.

To apply contact: Dr. Mo Motamedi, mmotamedi@hms.harvard.edu

CNY 149, 13th Street, Room 7-212, Charlestown, MA 02129

http://www.massgeneral.org/cancerresearch/research/researchlab.aspx?id=1...

 

 

Impulse Control in Alcohol-Using Adolescents, Dr. Silveri Lab, Neurodevelopmental Lab on Addictions and Mental Health, McLean Hospital/Harvard Medical School

To examine the impact of emotion on inhibitory control in adolescents with Alcohol Use Disorder (AUD), adolescents admitted to a dual-diagnosis residential treatment program were assessed on impulsivity measures, psychiatric and substance use disorders, and impulse control in the face of emotional distracters. Adolescents performed an emotional Go-NoGo task at intake and discharge from the two-week program. Adolescents with alcohol use disorders demonstrated higher negative urgency, less improvement in inhibitory control during positive emotional distractions at discharge, and a strong association between negative urgency and difficulties inhibiting a response to positive valence stimuli, compared to those without AUD. A lack of improvement on positive trials in the AUD group suggests ongoing elevated risk for impulsive action, in the context of heightened emotions. Understanding cognitive and neurobiological factors underlying impaired inhibitory control in the context of emotion, particularly in adolescents with AUD, may be helpful for improving treatment interventions in unique adolescent psychiatric cohorts. These findings suggest treatment for adolescents with AUDs could better address impulse control in emotionally positive as well as negative contexts, though further research is necessary to understand how negative and positive urgency scores differ in their relation to behavioral inhibition.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: Neuroscience or Psychology majors preferred. Interest in neuroimaging and psychiatry ideal. No skills required.

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill St., Belmont, MA 02478

http://nlamh.mclean.harvard.edu/

 

 

Metasurfaces for polarization optics, Dr. Capasso Lab, Applied Physics, School of Engineering and Applied Sciences

Light, or electromagnetic radiation, has three essential qualities: frequency (wavelength), intensity (brightness), and polarization. Polarization is the path along which the electric field vector oscillates and is fundamental in many fields of science and technology. The means for its control and measurement, however, largely rely on birefringent crystal waveplates, the same materials that led to polarization’s discovery in the 1600s. These plates must be precisely ground and present miniaturization and integration challenges.  In the Capasso Group, we develop “metasurfaces”, a term which refers to a new class of optics in which light is shaped by interaction with nano-scale structures rather than by bulk material refraction as in, e.g., a lens. Metasurfaces present a promising new frontier for polarization optics because these nanostructures can be engineered with very particular polarization properties.  In recent work, we have developed a metasurface that may act as a polarimeter, an instrument for measuring a light beam’s polarization state. Traditional polarimeters require many bulk polarization optics and, consequently, are large, expensive, and often limited in time resolution. Our metasurface polarimeter requires no additional waveplate optics other than the metasurface itself and we have shown that it may perform as well as an expensive commercial device.  We seek an undergraduate intern to further characterize the polarimeter and to aid in the development of the next generation of metasurface polarization optics applications, including, perhaps, a camera that can capture polarization images. The work sits at the intersection of optical technology (engineering) and fundamental optics (physics).

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: Familiarity with optics, Fourier analysis, and a basic knowledge of scientific computing, from coursework, are extremely helpful.  Skills such as CAD, electronics design, and basic machining of parts are also helpful but can potentially be learned as needed.

To apply contact: Dr. Federico Capasso, capasso@seas.harvard.edu

McKay 125 9 Oxford Street Cambridge, MA 02319

https://www.seas.harvard.edu/capasso/

 

 

Sensory Processing and its Relation to Brain Volum, Dr. Valera Lab, Psychiatry, MGH/Harvard

Studies suggest that children with ADHD exhibit more symptoms of sensory processing dysfunction (SPD) compared to healthy children. However, sensory processing has not yet been measured in ADHD using subscales for different sensory modulations (e.g., over-, under-sensitivity), studied in adults with ADHD, or examined in relation to brain volumes. Therefore, we assessed SPD in ADHD adults, and looked for relationships between SPD subscales and several brain volumes. We administered the Sensory Processing 3-Dimensions Scale (SP3D) to 24 ADHD and 29 healthy (HC) subjects, ages 18-50, who also underwent neuroimaging. The SP3D assesses sensory seeking (SS), over-responsivity (SOR), and under-responsivity (SUR) within different sensory domains. Structural imaging data were analyzed using FreeSurfer v5. Our findings indicate that, relative to healthy controls (HCs), subjects with ADHD scored higher on the SS and SUR subscales, and marginally higher on the SOR subscale. Furthermore, co-occurring anxiety mediated sensory over-responsivity in adults with ADHD. Amygdala volume correlated with SS and SUR total scores, and the posterior ventral diencephalon (pVDC) volume negatively correlated with the SOR total score in subjects with ADHD. These data suggest that adults with ADHD exhibit increased symptoms of sensory processing dysfunction with respect to sensory seeking and under-responsivity. Sensory over-responsivity, however, appears to be driven by co-occurring anxiety. Furthermore, because SS and SUR are associated with the amygdala, while SOR is associated with the pVDC, our findings indicate that SOR is supported by a different neural circuit than SS and SUR. Implications for these findings will be discussed.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Variable and open to discussion.

To apply contact: Dr. Eve Valera, eve_valera@hms.harvard.edu

Massachusetts General Hospital  Psychiatry, Rm 2660  149 13th St. Charlestown, MA 02129

https://www.nmr.mgh.harvard.edu/lab/valera

 

 

Dissecting the Impact of Glucotoxicity Resolution , Dr. Patti Lab, Section of Integrative Physiology and Metabolism

Background  Gene-environment interactions are at the nexus of insulin resistance and risk for type 2 diabetes, and in turn, are likely mediated by disordered epigenetic regulation of chromatin structure and transcription.  However our understanding of the molecular basis remains limited. Data indicate that high levels of circulating or cellular metabolites, such as glucose, can directly modify chromatin structure, causing transcriptional dysregulation and initiating the vicious cycle of insulin resistance. In addition, these epigenetic states can be transmitted through the paternal germ line to impact offspring metabolism. We aimed to dissect the impact of glucotoxicity on hepatic epigenetic regulation, transcription and offspring metabolism  Methods and Results  To study glucotoxicity and its reversal, we treated mice with SGLT-2 inhibitors (SGLT2i), a class of anti-diabetic drugs that increase urinary glucose excretion, reducing cellular glucose overload. Microarray and metabolomics analysis demonstrates that SGLT2i (1) induces a fasting-like metabolic state, (2) robustly modulates hepatic transcription (2522 genes pnom&lt;0.05), (3) reduces hepatic nutrient storage, (4) alters nutrient sensor activity, (5) alters expression/activity of multiple key TFs, (6) improves offspring metabolic phenotypes.   In light of such broad alterations in GEX, we hypothesize that resolution of hepatic glucotoxicity by SGLT-2 inhibitors remodeled chromatin structure in response to an altered intermediary metabolite landscape. We are currently analyzing epigenetic factors modified by resolution of glucotoxicity using Assay for Transposase-Accessible Chromatin (ATAC-seq) and chromatin immunoprecipitation (ChIP-seq). Moreover, we are analyzing paternal germ cell and offspring tissue epigenetic marks to determine potential mechanisms responsible for these exciting intergenerational effects.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Prior research experience is not required. 10 hours per week minimum

To apply contact: Dr. Mary-Elizabeth Patti, MaryElizabeth.Patti@joslin.harvard.edu

1 Joslin Place Boston MA 02215

 

 

 

Binge Drinking in Emerging Adulthood, Dr. Silveri Lab, Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital/Harvard Medical School

Binge drinking reaches a prevalence of 37.5% in individuals aged 18-25 years. It is therefore unsurprising that the highest rate of alcohol use disorders also occurs within this period of emerging adulthood. The widespread pattern of chronic, intermittent alcohol consumption seen in this age group coincides with the finalization of frontal lobe maturation, which may render emerging adults (EA) vulnerable to both immediate and long-term neurobiological consequences of binge drinking. The purpose of this study was to compare EA binge drinkers (BD) and light alcohol drinkers (LD) on clinical, cognitive and neuroimaging assessments to identify associations with binge drinking. Subjects were 18-25 year old BD (n=23) and LD (n=29), and underwent a battery of assessments as well as structural MRI and MRS brain scans. While BD demonstrated significantly greater drinking across all domains assessed, no significant differences were observed on clinical measures. Groups also did not differ across multiple cognitive domains, with the exception of a modest decrement in verbal learning scores for BD (p=.005). In contrast, multiple neurobiological differences were observed for magnetic resonance imaging and spectroscopy measures, including altered frontal lobe cortical thickness (p=.01), and altered GABA (p=.02), NAA (p=.02) myo-inositol (p=.05) and glutathione (p=.03) brain metabolites. These results suggest that while the frontal cortex is differentially sensitive to binge vs. light alcohol consumption, the observed neurobiological alterations in BD during EA do not manifest as clinical or cognitive impairments. Supported by K01AA014651 and R01AA018153 (MMS).

Number of hours/week: Negotiable: depends on arrangement

Requirements: Neuroscience or Psychology Majors preferred Interest in Neuroimaging and Psychiatry ideal No skills required

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill Street, Belmont MA 02478

http://nlamh.mclean.harvard.edu

 

 

Neurochemical correlates of adolescent impulsivity, Dr. Silveri Lab, Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital/Harvard Medical School

The objective of this study was to characterize in vivo brain GABA and glutamate levels in the anterior cingulate cortex (ACC) of the frontal lobe and in a region with strong functional and anatomical connections to the hippocampus, the medial temporal lobe (MTL). Twenty-four healthy adolescents completed the Barratt Impulsivity Scale (BIS), the Brief Sensation Seeking Scale (BSSS), and underwent proton magnetic resonance spectroscopy (MRS) at 3 Tesla using MEGAPRESS optimized to detect GABA. Metabolite data was acquired from separate single voxels placed in the ACC and right MTL and quantified using LCModel and normalized to creatine (Cr) levels. Significantly lower GABA/Cr was observed in the ACC compared to the MTL (p=.003), whereas Glu/Cr was similar across regions. Accordingly, the excitation:inhibition (Glu:GABA) ratio was significantly higher in the ACC (4.8 ± 0.8) compared to the MTL (3.1 ± 1.3, p=.003). Higher MTL Glu/Cr significantly predicted higher BIS total impulsivity scores (p=.006), and BSSS disinhibition (p=.008) and total sensation seeking (p=.024). Lower ACC GABA likely reflects a later maturation of this neurochemical in prefrontal cortex, relative to established Glu levels across regions. These data are the first reported evidence of a neurochemical correlate of heightened impulsivity and sensation seeking in adolescents observed prior to initiation of alcohol or drug use, observed in the MTL, but not the prefrontal cortex. These metabolite data may help probe the coupling between hippocampal and prefrontal regions, and risk-related behaviors that are developmentally adaptive, but may become maladaptive, particularly as adolescents initiate alcohol and drug use. 

Number of hours/week: Negotiable: depends on arrangement

Requirements: Neuroscience or Psychology Majors preferred Interest in Neuroimaging and Psychiatry ideal No skills required

To apply contact: Dr. Marisa Silveri, msilveri@mclean.harvard.edu

McLean Hospital, McLean Imaging Center, 115 Mill Street, Belmont MA 02478

https://http://nlamh.mclean.harvard.edu/

 

 

Amplification in Hearing: Mouse Finite-Element Mod, Dr. Puria Lab
Department of Otolaryngology, Harvard Medical School  Speech and Hearing Bioscience and Technology, Harvard University Graduate School of Arts and Sciences  Eaton-Peabody Laboratory, Massachusetts Eye and Ear

Our knowledge of cochlear mechanics is currently undergoing a revolution. While the basilar membrane (BM) has long been considered the principal structure in cochlear motion, new techniques such as optical coherence tomography (OCT) have instead revealed not only that the reticular lamina (RL) moves in a different pattern from the BM, but surprisingly it moves 3–10 times more at low input sound levels. Additionally, RL motion is closer to the inner-hair-cell stereocilia bundle, making it more relevant than BM motion for triggering the auditory nerve. We constructed a 3D finite-element model for the mouse cochlea and tested the model against recent non-invasive OCT vibrometry measurements. The model contains, a viscous-fluid environment, the key elements of organ of Corti (OoC) cytoarchitecture sandwiched between the BM and RL, including the piezo-like outer hair cell attahed to a Deiter’s cell and it’s Phalangeal process in a Y-shaped arrangement. The model allows clear relationships to be established between cochlear amplification and the structure and material composition of the OoC. The calculations demonstrate the high efficiency of the natural OoC cytoarchitecture and imply that the particular form of the Y-shaped combination is important for cochlear amplification. This improves our understanding of the various mechanical stages of hearing and deafness. [Work supported by NIH grant R01 DC 07910.]

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: No prior experience is required.

To apply contact: Dr. Sunil Puria, sunil_puria@meei.harvard.edu

Mass Eye and Ear  243 Charles Street Boston, MA 02114-3002

http://www.masseyeandear.org/research/investigators/p/puria-sunil

 

 

Cochlea Imaging with Optical Coherence Tomography, Dr. Puria Lab,   
Department of Otolaryngology, Harvard Medical School, Speech and Hearing Bioscience and Technology, Harvard University     Graduate School of Arts and Sciences     Eaton-Peabody Laboratory, Massachusetts Eye and Ear

Recent developments in Optical Coherence Tomography (OCT) allow measurements of cochlear motions through the bony cochlear wall without holes at spatial resolutions approaching about 10 um. We present measurements made with a commercial OCT system driven by custom software (VibOCT) that facilitates parallel-processing-based near real-time processing of measured whole A-line data to different frequency response measurements.  The 905-nm center wavelength Super Luminescent Diode (SLD) and high-speed (100 kHz) camera provide higher axial resolution (3 um in air) and temporal resolution than previous studies and a sub-nanometer noise floor in air. We gathered anatomical images of the gerbil cochlear apex in-vivo at higher resolution than available previously, sufficient to resolve individual outer hair cells, pillar cells, tunnel of Corti and inner sulcus regions.  Images from the 3rd apical turn show a bulging of Reissners membrane in-vivo that flattened post-mortem with a concomitant reduction in the distance between the Henson cell border and the stria vascularis wall. Vibrometry of the organ of Corti shows a low-pass characteristic in-vivo and post-mortem with a traveling wave-like phase delay similar to a recent study rather than the sharp tuning seen more basally. This system can provide valuable information on cochlear function, which is also useful for the development of detailed cochlear models of the passive and active gerbil apex. [Work supported in part by grant R01 DC07910 from the NIDCD of NIH]

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements:    No prior experience is required.

To apply contact: Dr. Sunil Puria, sunil_puria@meei.harvard.edu

Mass Eye and Ear     243 Charles Street     Boston, MA 02114-3002

http://www.masseyeandear.org/research/investigators/p/puria-sunil

 

 

Drive Mechanisms to Cochlear Hair Cell Stereocilia, Dr. Puria Lab
Department of Otolaryngology, Harvard Medical School     Speech and Hearing Bioscience and Technology, Harvard University     Graduate School of Arts and Sciences     Eaton-Peabody Laboratory, Massachusetts Eye and Ear

It has been long believed that inner hair cell (IHC) stimulation can be gleaned from the classic shear motion between the reticular lamina (RL) and tectorial membrane (TM). The present study explores this and other IHC stimulation mechanisms using a finite-element-model representation of an organ of Corti (OoC) cross section with fluid-structure interaction. A 3-D model of a cross section of the OoC including soft tissue and the fluid in the sub-tectorial space, tunnel of Corti and above the TM was formulated based on anatomical measurements from the gerbil apical turn. The outer hair cells (OHCs), Deiter’s cells and their phalangeal processes are represented as Y-shaped building-block elements. Each of the IHC and OHC bundles is represented by a single sterocilium. Linearized Navier-Stokes equations coupled with linear-elastic equations discretized with tetrahedral elements are solved in the frequency domain. We evaluated the dynamic changes in the OoC motion including sub-tectorial gap dimensions for 0.1 to 10 kHz input frequencies. Calculations show the classic ter-Kuile motion but more importantly they show that the gap-height changes which produce oscillatory radial flow in the subtectorial space. Phase changes in the stereocilia across OHC rows and the IHC are also observed.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements:    No prior experience is required.

To apply contact: Dr. Sunil Puria, sunil_puria@meei.harvard.edu

Mass Eye and Ear     243 Charles Street     Boston, MA 02114-3002

http://www.masseyeandear.org/research/investigators/p/puria-sunil

 

 

Re-writable Flat Photonics, Dr. Capasso Lab, SEAS

We develop a novel direct-laser writing approach to fabricating dielectric phase-change material (used in DVD re-writables) based metasurfaces. In particular, the realization of fully flat optical components is planned.  The advantage of this exciting method lies in the re-writability of such metasurfaces. Given a blank, any kind of metasurface can be written directly into the phase-change material and subsequently be erased.The work can be in either electromagnetic full-field simulations, hands-on optical setup building or data evaluation. 

Number of hours/week: Negotiable: depends on arrangement

Requirements: The ideal candidate should be strongly motivated, have experience in or a strong willingness to learn LabView, Matlab and numerical simulation methods and have an undergraduate level understanding of electrodynamics.

To apply contact: Dr. Federico Capasso, capasso@seas.harvard.edu

9 Oxford St 02138 Cambridge

https://www.seas.harvard.edu/capasso/

 

 

Imaging and computational neuroscience of sleep, Dr. Lewis Lab, Athinoula A. Martinos Center for Biomedical Imaging, MGH/HMS

http://web.mit.edu/ldlewis/www/

Number of hours/week: Negotiable: depends on arrangement

Requirements: No specific experience is required. Students seeking a computationally-oriented project should ideally have some programming and/or signal processing experience. Students seeking an experimentally-oriented project should be comfortable working with human subjects.

To apply contact: Dr. Laura Lewis, lauralewis@fas.harvard.edu

149 13th St Charlestown MA

 

 

The role of G proteins in gonadotropin expression, Dr. Kaiser Lab, Department of Medicine, Division of endocrinology, diabetes and hypertension, Brigham and Women's Hospital, Harvard Medical School

GnRH is a hypothalamic neuropeptide central to the initiation and control of the reproductive hormone cascade and hence fertility. Its action serves as a key regulatory point in the pituitary gland to control of the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn regulate gonadal function and gametogenesis.  GnRH is released in a pulsatile manner, with differential patterns of pulsatile GnRH release leading to differential synthesis and secretion of LH and FSH that are essential for control of female reproductive cyclicity and fertility. We aim to advance our understanding of the nature of the pituitary GnRH pulse frequency “decoder”, using both cell models and genetically modified mouse models. In mouse models, we will determine the importance of the Gαs and Gαq/11 proteins in gonadotropin expression and in normal reproductive function. In cell models, we will study the molecular pathways by which the differential gonadotropin expression occurs. The result of these studies will help to elucidate the details of the GnRH pulse frequency “decoder” and identify pathways and targets to modulate FSH separately from LH, with the potential to improve therapy for polycystic ovarian syndrome (PCOS) and other fertility disorders.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required.

To apply contact: Dr. Ursula Kaiser, ukaiser@bwh.harvard.edu

221 Longwood Avenue Boston, MA, 02115

 

 

Evaluation of Choroidal Lesions with Swept-Source , Dr. Miller Lab, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School

Purpose: To image choroidal lesions with swept-source optical coherence tomography (SS-OCT) and to identify the morphologic characteristics associated with optimal visualization. Design: Prospective, cross-sectional study Methods: Patients with choroidal melanocytic lesions &lt; 3 mm in thickness on B-scan ultrasonography were recruited.  All participants underwent color fundus photography (CFP), B-scan ultrasonography, and SS-OCT.  All images were evaluated by two independent graders. CFP were used to assess the degree of pigmentation of lesions. On SS-OCT we evaluated various qualitative (e.g. lesion outline, detection of scleral-choroidal interface, and quality of the image) and quantitative parameters (measurement of maximum lesion thickness and the largest basal diameter). Probability of optimal image quality was examined using ordered logistic regression models. The main outcome measure was quality of the choroidal lesion images on SS-OCT, defined as: optimal - all margins of the lesion well visible; suboptimal - at least one margin not properly imaged; or poor - more than one margin not properly imaged.   Results: We included 85 choroidal lesions of 82 patients.  The mean age of the patients was 65.8 ± 11.8 years. Forty-eight lesions (59%) were from female patients. There were 24 choroidal lesions (29%) for which image quality was classified as optimal, 31 lesions (37%) as suboptimal, and 30 lesions (36%) as poor. The factors associated with optimal image quality were distance closer to the fovea (OR 0.76, P &lt; 0.001), posterior pole location (OR 3.87, P = 0.05), lower ultrasound thickness (OR 0.44, P = 0.04), lighter lesion pigmentation (OR 0.12, P = 0.003) and smaller lesion diameter (OR 0.73, p&lt;0.001).  In the multi-variable analysis, closer distance to the fovea (OR 0.81, P = 0.005), lighter lesion pigmentation (OR 0.11, P = 0.01) and smaller lesion diameter (OR 0.76, p=0.006) remained statistically significant. Conclusion:  SS-OCT is useful in imaging most choroidal melanocytic lesions. Image quality is best when the choroidal lesion is closer to the fovea, has a smaller diameter and a lighter choroidal pigmentation.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required

To apply contact: Dr. John Miller, john_miller@meei.harvard.edu

243 Charles Street, Boston, MA, 02114

http://www.masseyeandear.org/research/ophthalmology

 

 

Artificial Intelligence in Medicine, Dr. Li Lab, Radiology, MGH, Harvard Medical School

Our group is dedicated to develop and bring forth the most advantage artificial intelligence system to the general healthcare community. Combining the talents from the field of data science, machine learning, radiology and clinical physicians, we are building smart systems to create value in the delivery of medical care and radiology services. Currently we have built deep-learning based medical image analytics systems for various clinical purposes, including pre-screening of critical lung conditions, emphysema early detection, and characterization of soft tissue cancer. Results reported in our preliminary experiments have shown increased diagnostic certainty with much decreased time on task for radiologists. In addition, we are working towards several major challenges in the current field of medical data analysis, including the adaptiveness to diverse data modalities and patient populations, the robustness to the noise in the data, and the capability to overcome the challenge of the lack for training samples. Based on our expertise in algorithm design and computational system, we have developed and published several advanced AI methodologies corresponds to each of the challenges above.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required.

To apply contact: Dr. Quanzheng Li, li.quanzheng@mgh.harvard.edu

55 fruit st. White 427,Boston, 02114

 

 

 

Development of a PET tracer for multiple sclerosis, Dr. Brugarolas Lab, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School

Central nervous system demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions including traumatic brain injury, stroke and Alzheimer’s disease. The ability to assess demyelination quickly and quantitatively is crucial for the diagnosis and treatment of these diseases. As current imaging approaches for demyelination rely on magnetic resonance imaging, which is neither quantitative nor specific for demyelination, we set out to develop a PET tracer for demyelination. In this project, we describe the development of a novel radioligand for brain imaging based on the FDA-approved drug for MS, 4-aminopyridine (4-AP). The Brugarolas lab seeks to develop new PET tracers for the brain and develop methods to image therapeutic antibodies by PET. The research employs synthetic chemistry, radiochemistry, biochemical assays and PET imaging in animal models of disease.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Prior experience in a chemistry or biochemistry lab is advantageous. Candidates will learn about radiochemistry and preclinical imaging with PET.

To apply contact: Dr. Pedro Brugarolas, pbrugarolas@mgh.harvard.edu

55 Fruit St, Bulfinch 051 Boston, MA 02114

http://gordon.mgh.harvard.edu/gc/

 

Towards a gene expression barcode from RNAseq data, Dr. Irizarry Lab, Biostatistics and Computational Biology, Dana-Farber Cancer Institute. Biostatistics, Harvard T. H. Chan School of Public Health

Understanding transcriptional programs in diverse cell types and tissues is of fundamental interest in biology. Is a gene active or turned “ON” in a given tissue type or biological sample of interest? This question though seemingly straightforward is complicated by biological stochasticity and leaky transcription on the one hand, and technical noise introduced by measurement technologies and quantification pipelines on the other. Next-generation RNA sequencing enables such investigation at a resolution and scale not possible before. In this work, we propose a statistical framework to model transcriptional activities of genes by leveraging publicly available bulk mRNA-seq data from 34 tissue-types in the Genotype-Tissue Expression (GTEx) project. The availability of large numbers of public data enable the possibility of developing unifying models for baseline RNAseq expression across different tissue types that are robust across sequencing technologies.  Expression values generated by RNA sequencing presents a rather complicated picture with some genes appearing bistable, while others more graded. We start with a bimodal framework of “off” and “on” states for each gene. We model transcriptional activity states using a 2-component hierarchical mixture model with one component representing “background” expression arising from technical sources or basal transcription, and the other component representing an “actively expressed” transcriptional state. We incorporate corrections for technical sources of error like gene length and GC bias. To motivate our model, we use prior knowledge from microarray data and generate priors informed from empirical data. For inference, we use probabilistic programming by Hamiltonian Monte Carlo sampling. With such a model in place, we can predict the gene expression activity state of a new biology sample.

Number of hours/week: Negotiable: depends on arrangement

Requirements: Statistical programming language (preferably R), basic knowledge of genomics

To apply contact: Dr. Rafael Irizarry rafa@jimmy.harvard.edu

 

Development of Motion-Free Tomographic Imaging, Dr. Gupta Lab, MGH radiology

CT is the clinical standard for diagnosing many emergent medical conditions, such as stroke and traumatic brain injuries.  Unfortunately, the size, weight, and expense of CT systems make them inaccessible for patients outside of large trauma centers, or in the developing world. We are designing a novel, modular x-ray system that will allow for CT scanners to be significantly lighter weight and cheaper.  This would expand access to this valuable diagnostic tool to austere environments such as rural and low-income communities, battlefield care, and extended space missions.    This is a multi-disciplinary project drawing on many fields including electrical engineering, nuclear science, machine learning, and medicine.

Number of hours/week: Juniors andSseniors can work 15-20 hrs/week

Requirements: We are looking for a students who can make a significant time commitment to this project, and are interested in pursuing a thesis or publication. No research experience is required, but some training in physics, engineering, or CS is highly recommended.

To apply contact: Dr. Rajiv Gupta, rgupta1@mgh.harvard.edu

149 13th street, Rm 2.406

http://www.massgeneral.org/doctors/doctor.aspx?id=17730

 

 

Synthesis of Platelet Imaging Conjugates, Dr. McCarthy Lab, Massachusetts General Hospital, Center for Systems Biology and Cardiovascular Research Center

In the clinical setting, blood vessel stenosis or the narrowing of a vessel, may impede adequate blood flow causing a number of pathological conditions, including angina and stroke.  Depending on the severity of the stenosis, the implantation of stents may be required to ensure patency.  Unfortunately, this intervention sometimes results in the formation of a clot within the stent occluding blood flow, potentiating catastrophic consequences.  We have thus developed a near-infrared imaging agent capable of binding to activated platelets, the hypothesized nidus for clot formation within the stent.  Based upon tirofiban, a widely utilized anti-platelet agent, we have generated a fluorescent derivative capable of detecting clots in vivo.  This agent has been extensively validated in murine models of thrombosis.  Current investigations are currently underway to determine if the agent is capable of detecting activated platelets adhered to implanted stents in rabbit models of stenosis.  Importantly, we will determine whether optimized optical fiber catheters capable intravascular NIRF imaging can provide high-resolution, sensitive readouts of molecular targets in coronary-sized vessels through blood, without the need for flushing, due to relatively low blood attenuation of NIR light. The ability to image platelet on healing coronary stents may offer new insights into pathogenesis of stent thrombosis, particularly late stent thrombosis in current and next generation drug eluting stents, especially when coupled with high-resolution structural imaging via intravascular ultrasound, or via single catheters integrating NIRF with optical frequency domain imaging, a leading modality for imaging coronary stent architecture.

Requirements: Organic chemistry lectures and lab

To apply contact: Dr. Jason McCarthy, jason_mccarthy@hms.harvard.edu

149 13th Street, 6th floor Charlestown, MA 02129

https://csb.mgh.harvard.edu/investigator/jason_mccarthy

 

 

The Mathematical Picture Language Project, Dr. Jaffe Lab, Department of Physics

We reevaluate ways that one can use pictures, not only to gain mathematical insights, but also to prove mathematical theorems. As an example, we describe ways that the Quon language, invented to study quantum information, sheds light on several other areas of mathematics. It results in proofs and new algebraic identities of interest in several fields. We explain how this picture language affords mathematical insights. Motivated by this success, we outline a picture program for further research, with the goal of unifying ideas from different subjects in mathematics and physics. We contextualize this program by citing examples of how pictures appear throughout mathematical history, from the schools of Euclid and Pythagoras to modern particle physics.

Number of hours/week: Negotiable: depends on arrangement

Requirements: No prior research experience is required.

To apply contact: Dr. Arthur Jaffe, jaffe@g.harvard.edu

17 Oxford St Cambridge, MA 02138

https://mathpicture.fas.harvard.edu

 

 

Elucidating the interplay of stress responses and energy stores, Dr. Blackwell Lab

The mechanisms by which organisms regulate stress responses and energy stores are likely to be ancient as they would have ensured the propagation of species during periods of drought and starvation. Cellular responses to stressors are orchestrated by specialized transcription factors, which fine-tune the expression of genes to either eliminate the stressor or ensure survival for long enough after the stress has ceded. In the nematode Caenorhabditis elegans, activation of the transcription factor SKN-1 (the sole ortholog of the mammalian NF-E2-related factors (Nrf) transcription factors) regulate genes involved in the response to oxidative stress and xenobiotics, extracellular matrix components, proteasome components and lipid metabolism genes. SKN-1 is required for lifespan extension mediated by reduced insulin/IGF signaling, rapamycin treatment, germline stem cell ablation, lipid overload, and by reactive oxygen (ROS) derived from either the mitochondria or the endoplasmic reticulum (ER). Current projects in our laboratory use a variety of genetic and molecular biology techniques in C. elegans taking advantage of its short life cycle of about 3 weeks, easy cultivation in big numbers and transparency allowing visualization of GFP-tagged genes. One project includes altering the aggregation profile of proteins that accumulate in neurodegenerative diseases through the activation of ER derived ROS. Another project analyses the nature of lipid signals in a genetic model of lipid overload that activates SKN-1 to regulate stress resistance, increased proteasome activity and longevity.

Requirements: No laboratory experience is required just great disposition and willingness to learn and do great science

To apply contact: Dr. T. Keith Blackwell, keith.blackwell@joslin.harvard.edu

One Joslin Place, Boston, MA

http://blackwellweb.joslin.harvard.edu/