Research Opportunities

Project Title: The Role of X-chromosome-linked Genes in Down Syndrome and Alzheimer’s Disease-related Pathology.

Project Goals: The project will be focused on the contribution of X-chromosome-linked genes that are dysregulated in Down Syndrome to the pathological cellular phenotypes and Alzheimer’s disease-related pathology. The project’s main goal will be to perform gene editing to downregulate the X-inactive specific transcript (XIST) in human Down Syndrome-derived induced pluripotent stem cells (iPSCs). The work will involve cell culture techniques, molecular biology, confocal microscopy, and more.

Time Commitment: Negotiable

Funding Source: NIA

General Research Focus of Laboratory: The lab’s research focuses on modulators of the medial temporal hippocampal system across the human lifespan, including aging, psychosocial and physiological stress, and lifestyle factors, such as exercise.

Research Projects Goals: We are currently starting up two new 5-year projects that have the goal to understand the impact of racism burden on brain and mental health in Black/African American adults from a cognitive neuroscience perspective. The first study, funded by NIA, focuses on impact of racism burden on cardiovascular disease risk and neurocognitive health in cognitively healthy older adults aged 65+. The second study, funded by NIMH, focuses on impact of racism burden on function of the medial temporal hippocampal system using fMRI in emerging adults aged 18-25 years.

Project Titles:
Project 1: Perceived racism, cardiovascular disease risk, and neurocognitive aging
Project 2: Psychosocial stress, cardio-respiratory fitness, and the medial temporal hippocampal system in Black emerging adults

Time Commitment: varies; negotiable.

Opportunity Start Date: Spring semester 2023 or Summer 2023

Type of Research: Basic science, Clinical Research and Public Health

Project Title: Mechanisms of Prion Protein Toxicity & Alzheimer’s Disease

Research Focus: My laboratory investigates the molecular and cellular mechanisms underlying two classes of human neurodegenerative disorders: prion diseases and Alzheimer’s disease.

Research Grants:

1. Mechanisms of Prion Protein Toxicity
   NIH/National Institute of Neurological Disorders & Stroke – 5R01NS065244-12
2. Discovering How Cu(II)/Zn(II) Uptake by the Prion Protein Controls Structure, Function and Neurotoxicity – The University of California, Santa Cruz NIH NIGMS – 5R35GM131781-04
3. Micro-Mapping to Identify Receptors for Toxic Protein Oligomers in Neurodegenerative Diseases – (PI)Merck, Sharp & Dohme LLC

Project Title: Group-based Mindfulness for Patients with Chronic Low Back Pain in the Primary Care Setting

Research Project Title: Group-based Mindfulness for Patients with Chronic Low Back Pain in the Primary Care Setting, (Optimizing Pain Treatment in Medical settings Using Mindfulness; OPTIMUM)

Research Description: To integrate a mindfulness-based pain management program (OPTIMUM) into the primary care setting by conducting a pragmatic clinical trial of Mindfulness-based Stress Reduction in three distinct health care systems.

Additional Research Grants:

1. Creating Opportunities for Underrepresented Researchers to Achieve Growth and Excellence (COURAGE). NIH/NIDDK – U24 DK132733
2. COPC Administrative Supplement to Group-Based Mindfulness for Patients with Chronic Low Back Pain in the Primary Care Setting. NIH/NCCIH – 3UH3AT010621-04S1
3. Mentoring and Patient-Oriented Research in Mind and Body Practices. NIH-NCCIH- K24AT011561
4. Building Up. To build the knowledge base of evidence-based interventions that advance the careers of postdocs, fellows, and junior faculty who are under-represented in the biomedical research workforce, we are proposing to test an intervention using near-peer mentoring. NIH-National Institute of General Medical Sciences – U01 GM132133

Type of Research: Clinical Research

Research Project: Our laboratory’s mission is to create methods to fit the science and not make science fit the methods, making us one of the most unique laboratories at BU. If you are a medical student who is interested to work at the interface of cutting-edge AI and application in healthcare, then you are welcome to reach out to us. Our lab has a healthy mix of individuals from computer science, medical school, electrical & computer engineering, bioinformatics and neuroscience. For more information about the Kolachalama Laboratory visit our website.

We are broadly interested in biomedical machine vision, representation learning and domain generalization, with applications in neurology and cancer. We are currently working with various members of the industry and investment communities to identify ways to translate software technologies to the clinic.

Research Grants: The American Heart Association, National Institutes of Health (NIA, NHLBI, NCI & NIDDK), the Karen Toffler Charitable Trust, Gates Ventures, Artificial Intelligence and Technology Collaboratories at NIA, and Johnson & Johnson Enterprise Innovation.
Type of Research: Translational research

Project Title: Melanoma and Epigenetics

Research Project: The Alani & Collard Lab is focused on understanding epigenetic reprogramming in melanoma and how this contributes to melanoma progression and therapeutic resistance. We have two main ongoing projects. In the first project, we are specifically interested in unveiling the role of the CoREST repressor complex in melanoma using a small molecule inhibitor. Here, we are investigating protein interactions, splicing, and chromatin organization. In the second project, we are investigating the role of lipid uptake and metabolism in melanoma epigenetic reprogramming and disease progression. Here, we are using in vitro models to assess the impact of lipid depletion on melanoma transcription, proliferation, migration, and invasion.

Mentors: Dr. Rhoda Alani, Dr. Marianne Collard, postdoctoral fellows, and PhD graduate students.
Availability: Summer 2024.
Time commitment: Negotiable with at least 3 consecutive hours in the lab at a time.

Project Title: The Role of Nuclear Corepressors NCoR1 and SMRT on Intestinal Metabolism in the Adult Mouse

Project goals:

1. To determine the role of NCoR1 and SMRT on intestinal glucose and fructose metabolism
2. To determine NCoR1/SMRT genomic recruitment and key transcription factors/nuclear receptors involved in glucose and fructose metabolism

Project Background: Thyroid hormone (TH) plays an essential role in maintaining homeostasis and regulating metabolism in all organ systems beginning with embryogenesis and continuing throughout life. TH action is mediated by the thyroid hormone receptor (TR), which is a nuclear receptor, and it’s coregulators. The nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) are two critical corepressors of the TR that inhibit gene transcription in the absence of TH. Repression is mediated by complexing with histone deacetylase 3 (HDAC3), which is stabilized by NCoR1 and SMRT. NCoR1 and SMRT are critical for maintaining metabolic homeostasis and we have recently reported the post-natal knock-out (KO) of NCoR1 and SMRT in tandem is not survivable and rapidly leads to weight loss, hypoglycemia, and hypothermia. Additionally, thyroid function shows non-thyroidal like illness with low free thyroxine levels. Further analysis suggested intestinal abnormalities including increase fecal caloric density which required exploration.

To further evaluate the intestinal findings, we used a tamoxifen-inducible villin Cre recombinase (VE-Cre-ERT2) to KO both NCoR1 and SMRT throughout the intestine. Mice were injected with tamoxifen at 8 weeks of age and metabolic parameters, including weight, glucose, and temperature were monitored. These mice then underwent both oral and intraperitoneal glucose tolerance testing (GTT) and metabolic phenotyping. Our preliminary data shows that intestinal KO of NCoR1 and SMRT leads to sustained weight loss up and hypoglycemia up to three weeks after tamoxifen injections. NCoR1 and SMRT double-KO is survivable in approximately 50% of mice. Oral GTT showed a blunted peak response to administration of glucose compared to intraperitoneal administration. Gene expression analysis showed alterations in intestinal carbohydrate transporters, including sodium-glucose transporters (SGLTs). Students will be mentored by myself and the other faculty and post-doctoral fellows in the lab including Dr. Sousa and Dr. Mendoza. We have lab meetings with Dr. Hollenberg.

Type of Research: Basic Science

Research Project: Continuous glucose monitoring: determinants and prediction of diabetes mellitus development in the Framingham Heart Study.

The goal of this project is to collect continuous glucose monitoring data in a healthy community-based sample to determine whether patterns identified in the rise and fall of glucose levels throughout the day can help predict risk of developing diabetes mellitus. Through linking patterns of dynamic glucose levels with diet and physical activity (among other factors like genetics, bacteria in the gut, and the prevalence of cardiovascular disease), this project may also lead to new discoveries that will tailor and target prevention of diabetes mellitus.

Project Title: Understanding how Vitamin D Enters and Exits Body Fat

Research Project: The goal of this research project is to determine how vitamin D is stored in body fat and how it exits when needed. This will be accomplished using labeled vitamin D that is added to cultured murine and human adipocytes.

Time commitment: Variable depending on what part the student would like to play in the project.
Funding: Institutional resources
Students will be mentored by Dr. Holick and Dr. Shirvani.

Project Title: Impact of Midlife and Late-life Intake of Flavonoid-rich Fruits on Dementia Risk in the Framingham Heart Study

Research Project: This project aims to investigate whether intake of fruits high in flavonoids in midlife and late-life are associated with reduced risk of dementia, including Alzheimer’s disease. Most studies to date focus on consumption of flavonoid-rich foods in older adults or during late-life, with findings to suggest that greater consumption of flavonoid-rich foods and fruits, such as blueberries, may reduce cognitive decline and dementia risk. Evidence from epidemiologic studies to support greater consumption of flavonoids earlier in life, such as midlife, in relation to dementia risk and cognitive decline is more limited, however. Despite the lack of epidemiologic studies looking at the impact of dietary intake of flavonoids earlier in life on the development of dementia, preclinical and animal studies provide evidence of the neurocognitive benefits of flavonoid-rich foods as early as childhood and adolescence. This suggests that greater consumption of fruits high in flavonoid content earlier in life may be as important or perhaps more important on lowering future dementia risk than later in life.

To test this hypothesis, we will leverage data collected on dietary fruit consumption from the Framingham Heart Study (FHS), which is a longitudinal, community-based cohort that has a rich collection of brain aging-related outcomes, including clinical diagnosis of dementia. An important aspect of FHS that is relevant to the objective of this project is that the age range of participants who enrolled in FHS generally spans from early adulthood (e.g., 20s-30s) to late-life (e.g., >65 years). This means that information on diet and specific foods, such as blueberries, is available to enable an analysis across different age periods. Coupled with dementia surveillance that has been ongoing since 1976, FHS is an ideal setting to study the impact of dietary fruit intake, especially fruits high in flavonoids, in midlife and late-life on the development of dementia. Findings from the project will advance understanding on whether the potential benefits of flavonoid-rich fruits on the brain and cognition are similar across different age periods, or whether greater dietary flavonoid intake from fruits at specific age periods, such as midlife or late-life, confers more benefits than compared to other age periods. This knowledge will help with promoting blueberries and other flavonoid-rich fruits as potential contributors to healthy brain aging.

Research Grant:U.S. Highbush Blueberry Council Dept of Agriculture

Type of Research: Public health, Epidemiology

Project Goals: The goal of the proposed project is to innovate a feasible and sustainable approach to improve the quality and experience of discharge teaching for patients with LEP. The TIDE trial (Tools for Improving Discharge Equity) is a randomized controlled trial to test the feasibility, acceptability, fidelity, and effectiveness of an enhanced discharge teaching strategy for patients with LEP. The enhanced discharge teaching strategy will create linguistically appropriate tools—including a medication calendar, pictographic, and audio recording of discharge teaching for patients for patients to replay at home after discharge—which nurses can use to improve the quality of discharge teaching.

I am looking for interested medical students to work during summer break full time as a research assistant on the trial. Strongly prefer someone who is fluent in one of the focus languages (Spanish, Haitian Creole, Cape Verdean, or Vietnamese). No funding available at this time but would be co-author on manuscripts with future opportunities to work with PI who has a NIH funded 5-year career development award.

Responsibilities Include but not limited to the following:

• Screen list of potential participants
• Prepare paperwork prior to participant approach
• Conduct informed consent conversations
• Observe discharge teaching interactions
• Assist with preparation of patient educational materials for clinical trial
• Collection and cleaning of data
• Assist PI with study protocols and IRB documents
• Develop case report forms and assist PI with standard operating procedures
• Coordinate study logistics
• Conduct informed consent with participants using interpreter when indicated
• Participate in research group meetings and check ins with PI
• Interface with clinical teams during recruitment and intervention
• Interface with hospital interpreters and nurses during intervention
• Maintain ethics and regulatory compliance documents
• Assist with preparation of manuscripts (including co-authorship)

Those interested should apply with cover letter, CV, and letter of recommendation to kirsten.austad@bmc.org

Project Title: Role of Peripheral Immune Cells in Cognitive Aging: The Framingham Offspring Study

Research Project: Role of peripheral immune cells in cognitive aging: The Framingham Offspring Study

The prevalence of dementia in the population is increasing and there are currently no effective therapies or blood-based biomarkers to detect people at high risk. We plan to investigate the role of circulating immune cells as risk factors for dementia, Alzheimer’s Disease and cognitive decline and to test whether associations differ in men and women and by genetic risk. This work will yield insights into the relationship between circulating immune cell types and brain aging, identify new biomarkers for cognitive decline, and may reveal novel therapeutic targets aimed at immune cell alterations to prevent and treat dementia.

Project Title: Neural Development & Craniofacial Disorders

The Lowery Laboratory has several possible research projects for medical students.

Two involve neural development:

1. Investigating basic mechanisms of axon guidance, specifically how cytoskeletal coordination is mediated by CKAP5 (basic science);
2. Investigating the embryonic functions of genes associated with neural developmental disorders (translational research).

Two involve craniofacial disorders

1. Investigating the mechanisms by which cells switch migration modes between group and individual during cranial neural crest cell migration (basic);
2. Investigating the functions of genes implicated in cleft lip palate disorders (translational).

Time commitment: Dependent upon goals of the student, but we can work with 10 hours to 40 hours/week.

Type of Research: Basic Science and Translational Research

Project Title: Plasma Cell Disorders: MGUS, Multiple Myeloma, AL amyloidosis

Research Interest: Plasma cell disorders – monoclonal gammopathy of undetermined significance, multiple myeloma, systemic immunoglobulin light chain (AL) amyloidosis. Major focus – translational research collaboration with the Center for Regenerative Medicine (CReM) and BU Amyloidosis Center which focuses on using novel disease models for hematologic malignancies to study the earliest signs of disease, test treatments and develop the most promising therapeutic agents for clinical trials.

Research Grant: Myeloma SPORE Career Development Award, International Myeloma Foundation Brian D. Novis Grant.

Type of Research: Basic Science, Translational, and Clinical Research

Project Title: Novel Plasma Exosome Biomarkers for Prostate Cancer Progression in Co-morbid Metabolic Disease

Research Project: Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease. Comorbid Type 2 diabetes (T2D), a metabolic complication of obesity, is prevalent among BMC cancer patients and associates with worse cancer outcomes for prostate, breast, head and neck, colorectal and several other solid tumors. However, the molecular mechanisms that explain these associations remain poorly understood. Emerging evidence shows that exosomes carry miRNAs in blood that encode the metabolic status of originating tissues and deliver their cargo to target tissues to modulate expression of critical genes. Exosomal communication potentially connects abnormal metabolism to cancer progression. New data support the hypothesis that T2D plasma exosomes induce epithelial-mesenchymal transition (EMT) in prostate cancer cells and drive disease progression. We recently showed that plasma exosomes from BMC subjects with T2D induce EMT features in prostate cancer cells. We demonstrated that specific exosomal miRNAs that are differentially abundant in plasma of T2D adults compared to nondiabetic controls (e.g., miR374a-5p, miR-93-5p and let-7b-3p) are delivered to cancer cells, thereby regulating critical target genes. Our previous reports show BRD4 controls migration and dissemination of castration-resistant prostate cancer, and transcription of key EMT genes; T2D exosomes require BRD4 to drive EMT. We validated our findings with gene set enrichment analysis of human genomic data from prostate tumor tissue. These results suggest novel, non-invasive biomarkers, and new approaches to evaluate and potentially block progression of prostate and other cancers, will benefit prostate cancer patients with comorbid T2D and refine clinical decision making. This NCI-supported project will investigate patient plasma exosomes, considering clinical variables like diabetes duration, metabolic medications, glucose control and demographic variables like age and race, to understand exosomal miRNA composition and how it relates to prostate cancer progression in patients with comorbid obesity and diabetes.

Time Commitment: Per week, 2 – 3 days of commitment to bench research (10 hours) will be minimally required to make acceptable progress.

Type of Research: Translational Research

Project Title: Developing Antibody-based Multipurpose Prevention Technologies for Contraception and Preventing Sexually Transmitted Infections

For the past 40 years I have directed a research laboratory that studies reproductive health, mucosal immunology and HIV sexual transmission. Our current goal is to develop multipurpose prevention technology (MPT) products that control the sexual transmission of viruses and provide contraception. My laboratory was among the first to develop quantitative culture and PCR methods for monitoring HIV levels in genital secretions, and established a number of human cervical and vaginal cell lines and reconstructed 3-D tissue models for studies on female reproductive health. Our recent research is focused on the topical use of monoclonal antibodies to prevent the transmission of HIV and HSV-2, and for contraception.

Research Grant: Antibody-based Contraceptive MPTs: Advancing the Human Contraceptive Antibody (HCA) through Clinical Trials. P50 HD096957

Project Title: Kidney Precision Medicine.

We have a number of R01 and U01 funded projects related to: kidney precision medicine; interventional trials of diabetic kidney disease; novel biomarkers of kidney disease; chronic kidney disease of uncertain etiology. Our approaches span epidemiology through transcriptomics. Students interested in translational research on chronic diseases like CKD can learn more Waikar Laboratory website.

Type of Research: Translational Research

Project Title: cardiovascular disease at the Intersection of another Organ Pathology

Research project description: I am a physician-scientist, and the director of Center of Cross-Organ Vascular Pathology. Our lab focuses on the cardiovascular disease at the intersection of other organ pathology. We use a range of models including cell-based models, animal models (mice, rats, zebrafish, rabbits and pigs) and strive to confirm our hypothesis in humans. Also, there are on-going clinical studies using novel devices to address key bottlenecks in the area of cardiovascular disease. Prospective students can choose projects under these three domains:

1. Cardiovascular complications in patients with chronic kidney disease: CVD burden is high in CKD patients, and hence our work probes the profound effects of CKD (uremia) on vascular diseases in these patients (uremic vascular disease). CKD is characterized by the retention of several metabolites called uremic toxins, which inflict organ damage including, cardiovascular complications. Leveraging cellular and molecular techniques, animal models such as rodents, zebrafish and pigs, we attempt to dissect the mechanism of toxicity of these solutes. We strive to validate those hypotheses in human subjects using various techniques including machine learning algorithms and artificial intelligence.
2. Angiogenesis and cancer: Cancer progresses through several steps characterized by a conversion of normal tissue states to anaplasia and neoplasia. While the tumor continues to grow in a conducive environment, it draws leash of blood vessels along with it. Angiogenesis, a process of generation of novel blood vessels is fundamental during the development and in various diseases such as cancer. Wnt signaling, a highly conserved oncogenic pathway. We examine the details of this pathway in fundamental understanding how Wnt signaling is regulated in various cancers.
3. Biomedical engineering approach addressing kidney problems: The era of precision medicine warrants a multi-pronged approach to develop better biomarkers or therapeutic targets. Leveraging a rich interdisciplinary network of biomedical engineers, computation biologists, synthetic chemists, polymer chemists and health economists. Kidney problems and its potential solution lend itself for the biomedical engineering approach. Two major areas remain the focus of our effort – bioimaging to evaluate the extent of kidney damage and vascular disease in CKD and bioengineering approach to develop targeted dialyzer membrane to remove cardiotoxic uremic solutes.

Type of Research: Translational Research

Project title: Study the efficacy and safety of a novel therapeutics lead in pre-clinical animal models of protein uric kidney diseases.

Project Goals and Description: The primary goal of this project is to test the efficacy and safety of a novel therapeutic lead in pre-clinical animal models of protein uric kidney disease. Protein uric kidney diseases such as nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) are significant causes of chronic kidney disease (CKD) and kidney failure worldwide. CKD affects an estimated 13% of the population (~37 million) in the US and over 850 million people worldwide and costs the US at least $50 billion each year. Protein uric kidney diseases are mainly caused by injury to podocytes that regulate glomerular filtration and prevent serum albumin from leaking into the urine (also called podocytopathies). Proteinuria/albuminuria is an early biomarker, risk factor, and surrogate outcome of CKD progression in patients. Injury to podocytes can cause podocyte foot process effacement and reduced slit-diaphragm density/length, which result in reduced podocyte buttress force on the gel-like glomerular basement membrane (GBM), leading to high GBM hydraulic conductivity with high albumin permeability and significant albuminuria. Treatments that enhance podocyte adhesion and maintain podocyte foot process structure can thus enhance podocyte buttress force and reduce albuminuria. However, no kidney podocyte-specific anti-proteinuria therapy is currently available for protein uric kidney diseases, posing a significant unmet medical need worldwide.
Read more about Dr. Lu’s research work.

Time Commitment: Consistent with the time commitment in the medical student’s Longitudinal Research Program (e.g., 6-10 hours per week during Fall and Spring semesters and full time in the summer as described in the medical school research track in LEADS). This project can also be performed as a Research Year Program for medical students.

Funding Sources: Government (e.g., NIH/NIDDK), Medical School (e.g., CTSI, MSSPP), Departmental (e.g., DOM).

Type of Research: Translational Research

Project Title: Lung Cancer Screening

Our group evaluates the utility of lung cancer screening, health disparities in lung cancer screening, and interventions to mitigate disparities in lung cancer screening and follow up care. Several projects are available for students with varying time commitments. Students would be mentored by Dr. Steiling, and closely work with the multi-disciplinary Lung Cancer Screening group, a nurse practitioner screening coordinator and patient navigators.

Type of Research: Clinical Research

Research Project: Our laboratory is focused on investigating the mechanisms of scleroderma fibrosis, with an special interest in the role of macropahges in fibrosis. We found that Fli1 deletion in myeloid cells may contribute to SSc fibrosis by enhanced expression of profibrotic markers, galectin-3 secretion, and activation of the mTORC1. We are now investigating the interplay between fibroblasts and macrophages in the development of fibrosis in scleroderma, using animal models of fibrosis and conditional knockout mice.

Research Grant: The project is funded through an R01 NIH grant named “The role of Fli1 in myeloid cells and its contribution to cardiac fibrosis”.

PI Dr. Bujor, 2 postdoctoral fellows and a Research Assistant are available to mentor students in the lab.

Type of Research: Basic Science

Project Goals and Description:

• Evaluation of music therapy to reduce anxiety in dementia patients.
  Group project – Time commitment is about 10 hours a week
• Evaluation of wearable device in PD patients.
  Group project – Time commitment is about 10 hours a week
• Evaluation of the Impact of weather on admissions for Parkinson’s disease patients.
  Group project – Time commitment is about 10 hours a week

Type of Research: Clinical Research

project Title: Neurocritical Care Research Focuses on Risk Stratification of Patients with Critical Neurologic Diseases

We are recruiting interested students to work with Dr. Ong, an Assistant Professor of Neurology at Boston University School of Medicine and lecturer at Harvard Medical School who specializes in Neurocritical Care whose research focuses on risk stratification of patients with critical neurologic diseases.

Project Title 1: Dynamic Models of Life-Threatening Mass Effect in Ischemic Stroke
Project Goal: Curate a BMC dataset of large MCA stroke patients and externally validate existing risk prediction models. Multiple positions available to work in tandem to
1. Identify and organize structured data from BMC of a large retrospective database of large ischemic stroke patients,
2. image feature measurement, and
3. Validation of existing risk models
Funding Source: NIH K23
Time Commitment: 10 or more hours a week.

Project Title 2: Identifying eye movements from electrooculography in comatose cardiac arrest patients
Project Goal: Collect data on eye movement from EOG on up to 200 comatose cardiac arrest patients to determine whether eye movement data improves neuroprognostication.
Funding Source: Simon Grinspoon Grant
Time Commitment: 5-10 hours a week.

Project Title 3: Pupillometry trends in patients with Traumatic Brain Injury (TBI)
Project Goal: Analyze pupillary data in patients with TBI from our existing retrospective database.
Funding Source: None
Time Commitment: 5-10 hours a week.

Project Title 4: Pupillometry trends in patients with Subarachnoid Hemorrhage (SAH)
Project Goal: Analyze pupillary data in patients with TBI from our existing retrospective database.
Funding Source: None
Time Commitment: 5-10 hours a week. Candidates ideally would have background and proficiency in writing protocols, handling datasets, R or Python. Students will gain experience in large retrospective clinical studies, dynamic risk prediction, machine learning models, and epidemiology under the guidance of Dr. Ong. Students will also have opportunities to gain experience in mixed effects modeling, natural language processing tools, and trajectory analysis under the guidance of collaborators including Dr. Josee Dupuis, Chair of Biostatistics at the BU School of Public Health, and Dr. Ludovic Trinquart, Associate Professor of Biostatistics at Tufts School of Medicine.

Students will have opportunities to work at both BU School of Medicine and with our active collaborators at Brigham and Women’s Hospital. Our interdisciplinary team includes Dr. Agni Orfanoudaki, Assistant Professor of Computer Science at Oxford University, and leaders in the field of Neuro-cerebrovascular disease including Drs. David Greer (Neurology), Stelios Smirnakis (Neurology) and Emelia Benjamin (Cardiology).

Type of Research: Clinical Research

Project Title: Parkinson’s Progression Markers Initiative
Project Goals and Description: APDA’s Centers for advanced Research support research trainees, fellowship programs, early-stage discovery, and later-stage clinical translation. The Centers facilitate investigative research into the causes, treatments, and ultimately a cure for Parkinson’s Disease (PD).

• Several other randomized controlled clinical trials
• Patient and care partner education projects
• Diversity, Equity and Inclusion in Parkinson’s disease projects

Funding Sources: Michael J. Fox Foundation for Parkinson’s Research (10/01/2010 – 01/31/2024)

Type of Research: Clinical Research

Project Title 1: Cerebral Small Vessel Disease (CSVD) and Stroke in Minorities

Project Goal: To characterize the relation of CSVD in brain imaging (CT and MRI) and stroke characteristics and outcomes in minorities.

Project Title 2: Inflammation and Enlarged Perivascular Spaces in the Framingham Heart Study

Project Goal: To study the relation of a comprehensive panel of inflammatory biomarkers (vascular and systemic) to topography and burden of enlarged perivascular spaces on brain MRI.

Ways you can get involved: Writing of research proposal, interpretation of results, preparation of abstract for presentation at a meeting, preparation of manuscript.

Learning Opportunities: Develop a research proposal, understand concepts on study design, statistical analyses, interpretation and presentation of results, poster/platform presentation, manuscript preparation and submission.

Time Commitment: 1 year. A timeline will be discussed on the initial meeting.

Type of Research: Clinical Research

Project Title: Stroke Epidemiology in a National Veterans Cohort

Project Goals and Description: VA Cardiovascular Epidemiology working group w/ collaborators from BU, BI, Brigham, Emory, and other institutions:

• E-cohort” w/ electronic health record, administrative data, pharmacy data, death records
• 10,000’s of stroke events
• Many ongoing and in-development projects on stroke risk prediction, US risk mapping, health disparities, statin use, and mortality outcomes

Time Commitment: 1–2-year commitment with close mentoring. Research proposal meetings Fridays 2x per month 10-11am

Type of Research: Clinical Research

Project Title: Clinical and diagnostic predictors of functional outcome in patients with Traumatic Brain Injury (TBI) at Boston Medical Center

Description of Research Project: The TBI study is a collaborative study between the departments of Neurology, Neurosurgery, Trauma surgery, Radiology and Anesthesia. The study aims to establish a TBI database at Boston medical center, which is the largest level 1 trauma center in New England. The other aims of the project are studying the clinical and diagnostic predictors of outcome in patients with TBI.

Type of Research: Clinical Research and Public Health

Project Title: Neurobehavioral Mechanisms Involved in Social Perception and Motivation in Individuals w/ and w/o Serious Mental Illness

1. Stable and dynamic neurobehavioral phenotypes of social isolation and loneliness in serious mental illness (R01MH125426)
2. Passive sensing of social isolation: A digital phenotyping approach (R01MH122367)
3. Modeling Dimensions of Individual Variation in Adaptive Foraging Decisions (R21MH124095)

These projects test hypotheses regarding motivation, social isolation, and loneliness in serious mental illness. One project examines the neurobehavioral mechanisms involved in social perception and motivation in individuals with and without serious mental illness, as well as associations with cardiometabolic health. In two projects we investigate the specific dynamic interactions among social experiences in daily life. We also conduct experimental research on decision making processes and links with psychopathology.

Funding:The above funded projects will last between 2 and 5 more years.

Type of Research: Clinical Research

Project Title: Immunobiology of the Retina

Within the healthy eye, mechanisms to control and manipulate immunity are necessary to preserve vision. Several specific neuropeptides present within the healthy eye regulate different immune cells and different immune cell functions. Collectively, they suppress inflammation and promote immune cell-mediated anti-inflammatory activity and immune-tolerance. Understanding how these neuropeptides alter immunity and work together to suppress inflammation profoundly impacts finding ways to reestablish health in the eyes following infection, graft rejection, autoimmune disease, and trauma. Our experimental approach uses molecular biology, biochemistry, histology, immunohistochemistry, flow cytometry, gene delivery, cultured immune cells, and immune model techniques. Each student has a separate research opportunity linked to the general study of vision science and immunobiology.

Type of Research: Basic Science.

Project Title: Defining Mechanisms of Genome Instability

General Research Areas Include:

• Defining mechanisms of genome instability
• Identifying regulators of the Hippo Pathway
• Working with mouse models of sarcoma and melanoma
• Using synthetic-lethal screens to identify cancer-specific gene dependencies

Funding: There is currently no budgeted salary support available to medical students to work on these projects.

Time Commitment is variable, depending on the project and whether it is during the academic or summer term.

Type of Research: Basic Science

Research Project: Our research is focused on elucidating the molecular mechanisms and regulation of protein synthesis (translation) in human cells and the integrated stress response (ISR). Dysregulated ISR is a causative factor in Alzheimer’s Disease and other neurodegenerative disorders.
Specific areas of interest include:

• The architecture of the translation initiation complexes, the molecular mechanisms of key steps in the process, and their regulation.
• The coordination between translation initiation and ISR and how ISR inhibitors can be used to protect neurons from apoptosis.
• Quantitative analysis of the translation process in dividing vs. resting cells or under stress conditions. In particular, we want to understand how the entire protein synthesis machinery in dividing cells is reset to a new, more efficient state by changes in the concentrations of ribosomes and proteins, and modulation of individual binding affinities and reaction rates, e.g. by phosphorylation.

Time Commitment: Interested students need to be able to commit to at least 10 hours a week on average. The nature of the work here requires blocks of at least a few hours, preferably on consecutive days.

The students will be mentored by me, with the help of Paul Wagner, a research technician in the laboratory.

Type of Research: Basic Science

Jiang Laboratory Research Focus: Obesity and Systemic Inflammation

1. Understanding the role of neutrophils in the development of obesity-related systemic inflammation, tissue damage, and remodeling.
   Using a quantitative serum proteomic approach, we discovered that obesity leads to the imbalance between serine protease neutrophil elastase and serine protease inhibitor alpha-1-antitrypsin both in mouse models and human subjects. Our studies also revealed that obesogenic diet feeding induces alternation of hematopoiesis with a dramatic increase of pro-inflammatory neutrophil production and pro-inflammatory phenotype in mice. Interestingly, mice lacking neutrophil-specific protease neutrophil elastase are resistant not only to diet-induced neutrophil production but also to obesogenic diet-induced vascular damage, adipose inflammation and fibrosis, nonalcoholic steatohepatitis (NASH), and insulin resistance. We are in the process to study how nutritional factors are involved in the regulation of neutrophil differentiation, immune cell interactions with vascular wall and tissue-resident cells, and how these processes are related to the development of systemic inflammation, NASH, adipose tissue fibrotic remodeling, and metabolic disorders.
2. Neutrophils play a pivotal role in obesity-related vascular injury and vascular aging.
   Our study revealed that neutrophils contribute to obesity-related vascular leakage and immune cell infiltration in adipose tissue by releasing neutrophil elastase. The latter increases vascular permeability through activating protease-activated receptor 2 (PAR2) signaling in vascular endothelial cells. Our recent studies also revealed that neutrophils are involved in vascular aging and related arterial stiffness. We are currently investigating molecular and cellular mechanisms by which obesity and aging regulate the interactions between neutrophils and vascular cells.

We are applying cell culture and animal models to our study using a variety of basic techniques. We encourage medical students to visit the lab and discuss potential projects.

Funding: Funded by an NIH R01 grant.

Type of Research: Basic Science

Research Project: Telomere elongation is a requisite for cellular immortality and a hallmark of cancer cells. Most cancer cells rely on reactivation of the enzyme telomerase or activation of the alternative lengthening of telomeres pathway (ALT) to promote telomere elongation. The prevalence of ALT across all cancers is approximately 10%, however the prevalence of ALT in cancers of neuroepithelial and mesenchymal origin are estimated to be over 50%. Although comprehensive studies in children are limited, analysis in our lab suggests that ALT is prevalent in approximately 95% of pediatric osteosarcoma. Given that ALT activity is absent in normal tissue, targeting the ALT mechanism has become an attractive target in the treatment of ALT positive cancers including pediatric osteosarcoma. While several therapeutic modalities have showed promise in vitro, there are currently no clinical trials specifically for the treatment of ALT positive cancers. Therefore, defining the genetic and molecular underpinnings of ALT activity could not only identify genetic vulnerabilities in the ALT pathway, but drive therapeutic development for the treatment of ALT positive cancers.

• Specific Aim 1: Define the prevalence of TERC mutations in pediatric osteosarcoma. Our preliminary data demonstrate that approximately 30% of our pediatric osteosarcoma samples (N=20) harbor mutations in the TERC gene. To increase the power of our analysis we will acquire 50 new tumors from the Children’s Oncology Group and analyze the TERC gene using custom designed primers that extend coverage into both the promoter and 3’ UTR. In parallel, we will determine ALT status by quantifying C-rich extrachromosomal telomeric repeats (C-circles) from gDNA. C-circles are the gold standard in the field for analysis of ALT activity.
• Specific Aim 2: TERC mutations as an early driver event in the genetic evolution of ALT positive tumors. Our identification of TERC mutations in a subset of ALT tumors suggests that functional inactivation of telomerase may increase the likelihood of ALT activation. Therefore, in collaboration with the Data Science Core we will use whole-exome sequencing (including custom designed TERC probes) in TERC mutant ALT positive tumors to infer genetic evolution of pediatric osteosarcoma using a computational pipeline called PhylogicNDT.

Mentoring: Myself and a senior Graduate Student (Joshua Keegan)
Funding: Start-up with the goal of generating preliminary data to acquire funding.
Type of Research: Basic Science

Research Project: Dr. Lehman’s research is focused on characterizing the role played by muscle thin filaments in regulating cardiac and smooth muscle contractility. To accomplish his research goals, he takes a structural approach involving a combination of molecular biology, cryo-electron microscopy, and image processing as well as uses computational tools such as molecular dynamics and protein-protein docking protocols. His laboratory was the first to directly visualize the steric-blocking mechanism of muscle regulation by identifying the positions assumed by tropomyosin on actin in the presence and the absence of Ca2+. His molecular models of actin-containing thin filaments provide a framework to investigate disease-bearing mutations leading to cardiomyopathies and for drug discovery to counteract corresponding disease development.

Dr. Lehman’s team consists of Drs. Rynkiewicz, Karpicheva and Ramachandran. He collaborates actively with Dr. Bullitt in the PP&B department as well as with colleagues at Yale University, UMass-Lowell, Johns Hopkins University, the University of Washington and the University of Kent.

Research Grant: NIH- Thin Filaments and Muscle Regulation; Computational Pipeline for Identification of Disease-Causing Variants in Genes of the Cardiac Sarcomere; and Pathogenesis and In Vivo Suppression of Thin Filament Based Cardiomyopathies.
Type of Research: Basic Science