The CDI and the Physician-Scientist Development Award have played a key role in helping me become an NIH independent investigator. I am truly grateful to them for helping advance my career.

Oluwaseun Johnson-Akeju, MD
2011 Physician-Scientist Development Award Winner

2020 Physician/Scientist Development Award Recipients

David A. AlagpulinsaDavid A. Alagpulinsa, PhD
Department of Medicine, Mass General Vaccine & Immunotherapy Center
Research Fellow in Medicine, Harvard Medical School

Dr. Alagpulinsa is a Research Fellow in Medicine at the Mass General Vaccine & Immunotherapy Center and Harvard Medical School. He earned a PhD in Interdisciplinary Biomedical Sciences from the University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. His research at the Vaccine & Immunotherapy Centers involves regenerative medicine in the context of type 1 diabetes. Dr. Alagpulinsa is an awardee of the Mass General ECOR Tosteson & Fund for Medical Discovery Postdoctoral Fellowship and was the Mass General 2019 institutional nominee for the American Diabetes Association Pathway to Stop Diabetes Initiator Award.

Abstract: Redirecting and recruiting endogenous stem/progenitor cells and immunoregulatory cells for in situ islet regeneration in type 1 diabetes

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta cells of the pancreatic islets, resulting in insulin deficiency and hyperglycemia. The incidence of this incurable disease is on a global rise, affecting 64, 000 Americans annually and causing an annual loss in income and healthcare expenditure of $14.4 billion to the country. Even the strictest blood glucose monitoring and insulin injection regimen, which is the current gold standard of care, does not achieve tight physiological glucose control in the majority of patients. Consequently, most patients ultimately succumb to T1D-related complications. The human bone marrow (BM) is endowed with stem and progenitor cells and regulatory T cells (Tregs) that have the capacity to abrogate the autoimmune response against beta cells, while supporting their regeneration. Unfortunately, the BM is also “sick” in T1D, causing impaired function and peripheral mobilization, which promotes inflammation and insulitis. The overall goal of this research project is to understand how T1D impacts the BM environment using single-cell RNA sequencing analysis and to design pharmacological tools to efficiently mobilize BM stem and progenitor cells and Tregs into the blood circulation and islet-targeting nanoparticles loaded with chemokines to recruit these cells specifically into the islets to dampen the autoimmune response and elicit beta cell regeneration to treat T1D.


Ibiayi Dagogo-JackIbiayi Dagogo-Jack, MD
Department of Medicine, Cancer Center
Instructor in Medicine, Harvard Medical School

Dr. Ibiayi Dagogo-Jack received her bachelor’s degree from Vanderbilt University and her medical degree from the University of Chicago Pritzker School of Medicine. She trained in internal medicine at Brigham and Women’s Hospital. Following residency, she completed hematology/oncology fellowship in the combined Massachusetts General Hospital/Dana Farber Cancer Institute program. She is a medical oncologist in the Massachusetts General Cancer Center where she specializes in thoracic cancers and conducts clinical and translational research. Her research focuses on understanding mechanisms underlying response and resistance to novel targeted therapies, investigating the role of non-invasive assays in molecular surveillance and detection of lung cancer, and developing clinical trials of novel drug combinations in lung cancer and mesothelioma. In addition to the CDI PDSA, her work is currently supported by a K12 award and industry grants. She is a past recipient of ASCO Merit and Young Investigator Awards, pilot grants from the American Cancer Society and MGH Center for Innovation in Early Cancer Detection, and the CDI Sanchez-Ferguson Award.

Abstract: Strategies to Detect and Overcome Bypass Track Activation in ALK+ Lung Cancer

Lung cancers with anaplastic lymphoma kinase (ALK) rearrangements depend on ALK signaling and are initially markedly sensitive to ALK targeted therapies. However, the majority of these tumors will eventually develop refractoriness to ALK targeted therapy due to adaptations that promote dependence on other growth signals. In current practice, "ALK-independent" growth signals are most often identified through direct analysis of biopsies obtained through invasive procedures or laboratory studies of cell lines derived from these biopsies. Through this grant, we will explore whether less invasive plasma analysis can identify genetic and proteomic alterations that are critical to survival of resistant ALK-positive lung cancers. Furthermore, as we have shown that aberrant activation of the MET receptor contributes to 20% of relapses on ALK therapy and demonstrated that inhibiting both ALK and MET overcomes this type of resistance in preclinical models, we will conduct a clinical trial to evaluate the activity of the combination in patients with ALK-positive lung cancer with acquired MET signaling. As there are no approved therapies for ALK-independent resistance and understanding of the molecular drivers of this important form of resistance is limited, these analyses have the potential to immediately impact patient care and inform future therapeutic strategies.


Christian Lacks Lino CardenasChristian Lacks Lino Cardenas, PharmD, MSc, PhD
Department of Medicine, Cardiology Division
MGH Cardiovascular Research Center
Instructor in Medicine, Harvard Medical School

Dr. Lino Cardenas is an investigator in the Massachusetts General Hospital Cardiology Division and is an Instructor in Medicine in the Lindsay laboratory within the Mass General Center for Cardiovascular Research (CVRC). Dr. Lino Cardenas received his Doctor of Pharmacy degree with honors from the University of Saint Mary (Arequipa-Peru). He pursuit his education with a Master of Sciences in the field of Microbiology and Genetics and a PhD in Molecular biology and Genetics from the University of Lille2 (France). He completed his post-doctoral training in the division of Pulmonary, Allergy and Critical Care Medicine at UPMC (2013) and Cardiovascular Research Center at Mass General (2017). Dr. Lino Cardenas’s investigations have led to the discovery of a novel pathologic epigenetic complex (HDAC9-MALAT1-BRG1) triggered by multiple vascular smooth muscle cell-related diseases. In addition, his research focus on the understanding of molecular mechanisms that effect the homeostasis of vascular tissue for the design of therapeutic interventions for the treatment of patients with CVDs.

Abstract: HDAC9 is a novel negative regulator of autophagy pathway in Thoracic Aortic Aneurysm

Aortic aneurysm is a common human condition, accounting for greater than 17,000 deaths annually in the United States. Aortic aneurysm places individuals at risk for aortic dissection (AoD), a life-threatening complication of aortic dilation, a malady with mortality rates measured at 1-2% per hour. During aortic aneurysm progression, vascular smooth muscle cells (VSMC) undergo dramatic changes in cellular phenotype. Large scale rearrangements in cellular metabolism, impaired autophagy signaling, loss of cellular contractile elements and expansion of synthetic capacity. Our previous work has found that HDAC9 mediates the epigenetic downregulation of VSMC contractile genes via recruitment of the methyltransferase EZH2, the catalytic subunit of the PolyComb Repressive complex 2 (PRC2). Interestingly EZH2 is a negative regulator of autophagy activity with detrimental effects on VSMC survival. Autophagy is an evolutionarily conserved, tightly regulated process through which cells deliver unnecessary or potentially dangerous cellular materials in double-membrane vesicles for degradation via fusion with lysosomal compartments. Our preliminary data indicates that in TAA models, HDAC9 binds to chromatin regions at autophagy-related gene-loci which associates with the accumulation of autophagy vesicle and cytotoxic materials (matrix proteases), indicating abnormal autophagy flux. We expect that this study will lead to an in-depth mechanistic understanding of the regulation and function of autophagy in normal vascular tissue and aneurysm disease and will provide insights into precise targeting of autophagy for aortic aneurysm treatment.


Nneka N. UfereNneka N. Ufere, MD
Department of Medicine, Gastroenterology Division, Liver Unit
Clinical and Research Fellow, Harvard Medical School

Dr. Ufere is currently a Transplant Hepatology fellow in the Division of Gastroenterology within the Department of Medicine at Massachusetts General Hospital and Harvard Medical School in Boston, MA. She completed an A.B. in Molecular and Cellular Biology with a minor in Psychology at Harvard College in 2008. She attended Washington University in St. Louis School of Medicine where she completed her medical degree in 2012 and was inducted into the Alpha Omega Alpha Honor Medical Society. She completed her residency training in internal medicine at Massachusetts General Hospital, where she also served as a Chief Medical Resident during the 2016-2017 academic year. She is currently in her postdoctoral research fellowship and is pursuing a Master of Science in Clinical Epidemiology degree at the at the Harvard T. H. Chan School of Public Health. She will complete her advanced fellowship in Transplant Hepatology in 2021.

She is a member of the Massachusetts General Hospital Cancer Outcomes Research Program and the Mass General Liver Unit, and her research interests center around palliative and supportive care and informed decision-making with the goal of developing interventions aimed at improving the quality of life and end-of-life care for patients with advanced liver disease and their caregivers.

Abstract: A Randomized Study of Inpatient Palliative Care for Patients with End-Stage Liver Disease

End-stage liver disease (ESLD) is an irreversible condition marked by poor quality of life, high symptom burden, and a median survival of less than 2 years in the absence of liver transplantation. While liver transplantation improves outcomes for transplant candidates, the diagnosis of ESLD remains a terminal one for thousands of patients annually who die while awaiting a donor organ or are deemed ineligible for transplant. Despite their poor prognosis, the majority of patients with ESLD have frequent hospitalizations and receive intensive care in their last months of life.

Specialty palliative care clinicians are experts in managing complex symptoms, helping patients cope with their illness, enhancing patients’ illness and prognostic understanding, and supporting patients with advance care planning. However, palliative care is underutilized for patients with ESLD, despite studies showing that palliative care improves quality of life and symptom burden and reduces healthcare utilization in patients with serious illnesses.

We have developed a longitudinal inpatient palliative care intervention tailored to the unique physical, psychological, and end-of-life care needs of patients with ESLD. In this proposal, we will conduct a prospective randomized study to assess the feasibility, acceptability, and preliminary efficacy of this intervention versus usual care alone on improving quality of life and symptom burden and reducing healthcare utilization for 100 patients with ESLD.

Prior Year Winners

2019

George Alba, MD

George Alba, MD
Division of Pulmonary & Critical Care
Department of Medicine
Instructor in Medicine, Harvard Medical School

Dr. Alba is a physician-investigator in the Division of Pulmonary and Critical Care at Mass General. Dr. Alba received his bachelor’s degrees in English Literature and Biology from Washington University in St. Louis and earned his MD at the Mount Sinai School of Medicine. He completed his Internal Medicine and Pulmonary and Critical Care training at Mass General before joining the Division of Pulmonary and Critical Care as an Instructor in Medicine at Harvard Medical School in 2018. Dr. Alba pursued a postdoctoral research fellowship in the laboratory of Dr. Bradley Maron at Brigham and Women’s Hospital where he completed a National Research Service Award funded by the National Heart, Lung, and Blood Institute of the NIH to study platelet-endothelial interactions in the pulmonary circulation. He is a recipient of the NIH Loan Repayment Program and the Harvard KL2/Catalyst Medical Research Investigator Training (CMeRIT) award and is a finalist for the American Heart Association (AHA) Cournand and Comroe Early Career Investigator Award.

Abstract: Targeting NEDD9 with a Novel Antibody to Inhibit Platelet-Endothelial Cell Adhesion Selectively in the Pulmonary Circulation

Thrombotic disorders of the pulmonary circulation, including pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH), are estimated to affect over 1 million people in the United States every year, accounting for 1 in 8 deaths worldwide and costing over $1.5 billion U.S. dollars annually. The current standard of care treatment is anticoagulant or thrombolytic drugs; however, these therapies do not target molecular mechanisms underlying pulmonary thrombosis specifically and are associated with a high rate of major adverse clinical events due to off-target drug complications such as life-threatening hemorrhage in other vascular beds. Therefore, developing a therapy that is selective to the pulmonary circulation is anticipated to provide a superior therapeutic advantage compared to the current standard of care. We demonstrated that NEDD9 is a hypoxia-sensitive protein that is selectively upregulated on the luminal aspect of human pulmonary artery endothelial cells and binds directly to platelet-surface P-Selectin to promote pulmonary thrombosis. We developed a novel antibody that targets the NEDD9-P-Selectin binding region to prevent platelet-endothelial adhesion in vitro. We now aim to demonstrate if it can prevent pulmonary thrombosis and pulmonary hypertension in vivo with the goal of translating this into a novel therapeutic strategy for patients.


Sophia Kamran, MD

Sophia C. Kamran, MD
Department of Radiation Oncology, Genitourinary Service
Massachusetts General Hospital Cancer Center
Assistant Professor of Radiation Oncology, Harvard Medical School

Dr. Kamran is a radiation oncologist at the Massachusetts General Hospital Cancer Center and Assistant Professor of Radiation Oncology at Harvard Medical School. In her clinic, she specializes in the treatment of genitourinary cancers. Her research interests focus on the application of computational genomic approaches to characterize tumor evolution to treatment and understand mechanisms of toxicity and resistance to radiation and chemoradiation. Her long-term goal is to use these approaches to guide the design of clinical trials of high-precision radiation therapy to enable personalized approaches to delivery of radiation therapy for patients with genitourinary cancers. Her research has received distinctions from the American Society for Radiation Oncology (Basic/Translational Science Research Award) as well as the Mass General Department of Radiation Oncology William Shipley Research Award. Dr. Kamran was recently nationally recognized as a “40 Under 40 in Cancer Rising Stars and Emerging Leaders” by the Lynx Group/McGivney Global Advisors. In addition to the CDI Physician and/or Scientist Development Award, she is also the recipient of the inaugural Loeffler Team Science Seed Grant for her translational work in immunoradiotherapy.

Dr. Kamran holds a bachelor’s degree in Biological Engineering from the Massachusetts Institute of Technology, which she attended as a Gates Millennium Scholar. She received her medical degree cum laude from Harvard Medical School. During her medical training, she completed a Howard Hughes Medical Student Research Fellowship. She completed a transitional year internship at Memorial Sloan Kettering Cancer Center, and residency training at the Harvard Radiation Oncology Program.

Abstract: Prospective Validation of Single Nucleotide Polymorphisms as Predictors of Toxicity Following Radiation Therapy for Prostate Cancer

Prostate cancer (PC) is the most common malignancy among men in the United States. Prostate-directed radiation therapy is an effective treatment for localized PC but it can be associated with long-term bladder, bowel, and sexual toxicities that adversely impact quality of life (QOL) in PC survivors. Long-term QOL is key in this population given high cure rates and long natural history. There is a need for biomarkers that can accurately predict individualized radiation toxicity risk and thus enable tailoring of treatment. Emerging data suggest that inherited genetic differences may impact radiosensitivity. Single nucleotide polymorphisms (SNPs) have been reported as predictors of toxicity after radiation but have not been independently validated in prospective, prostate-specific cohorts. The overarching hypothesis of this project is that individual genetic variations through SNPs mediate normal tissue toxicities induced by radiation. Using samples from patients prospectively enrolled on an ongoing multicenter national randomized phase III trial evaluating proton- versus photon-beam radiation therapy in early-stage PC, we seek to validate previously identified SNPs associated with radiation toxicities using high-quality, prospectively collected toxicity and patient-reported outcome data. Validated SNPs can serve as biomarkers for predictors of radiation-specific toxicity and patient-reported long-term QOL that can guide and personalize PC treatment.


Patricia Musolino, MD, PhD

Patricia Musolino, MD, PhD
Department of Neurology, Division of Child Neurology, Critical Care and Stroke
Co-director Pediatric Stroke and Cerebrovascular Service
Affiliated faculty, Center for Genomic Medicine
Assistant Professor of Neurology, Harvard Medical School

Dr. Musolino is a critical care and vascular neurologist with expertise in white matter disorders and cerebrovascular biology. She is assistant professor of neurology at Harvard Medical School and the co-director of the pediatric stroke and cerebrovascular service at Massachusetts General Hospital. Dr. Musolino's clinical and research expertise revolves around the translation of discoveries in human genetics to clinical application in white matter and cerebrovascular disorders. Following training in neurosciences, imaging and molecular biology, acquired during her MD and PhD in her native Argentina and post-doctoral training at Harvard, Dr. Musolino completed dual training in pediatric and adult neurology with specialization in critical care and stroke at Mass General. Dr. Musolino’s laboratory focuses on leveraging insights from neuroimaging in patients and in-vitro gene-editing tools to understand how single gene mutations alter blood-brain barrier and cerebrovascular function in order to find better therapies and improve the quality of life of patients with rare genetic disorders. This novel approach has led to multiple high-impact publications and the development of pre-clinical tools to develop gene targeted therapies for single gene disorders causing neuroinflammation and stroke at a young age, including ALD, ACTA2, SAMHD1, CADASIL and COL4A1. Working hand in hand with patients and advocacy groups, Dr. Musolino is also developing an international network and resources to maximize the life potential of children and young adults affected by these disorders. Dr. Musolino is the recipient of several awards from NINDS, the Hearst and Child Neurology Foundation, Mass General Executive Committee on Research and the 2017 Herbert Pardes Clinical Research Excellence Award from the National Clinical Research Forum for the first gene therapy trial in a cerebral demyelinating disorder.

Abstract: Brain Vessel Permeability in Cerebral Adrenoleukodystrophy

Cerebral Adrenoleukodystrophy is a devastating inherited disease that causes inflammatory cells to infiltrate the brain, leading to progressive degeneration, vegetative state and death in months to years. Unfortunately, current therapies either fail to prevent cerebral disease or carry high toxicity and mortality. In this project we will study how the gene defect changes the brain vessel permeability to allow access of inflammatory cells to the brain using laboratory tools at the bench. If validated by this study, our approach sets forth a successful strategy for identifying factors that contribute to the development of cerebral degeneration and a laboratory tool urgently needed to screen for new therapies that are more targeted and less toxic.


Erika Warner, ScD, MPH

Erica T. Warner, ScD, MPH
Department of Medicine, Mongan Institute, Clinical Translational Epidemiology Unit
Assistant Professor of Medicine, Harvard Medical School

Dr. Warner is an Assistant Professor in the Department Medicine at Harvard Medical School and an Assistant Investigator at Mass General, where she conducts epidemiological research on cancer in the Mongan Institute’s Clinical Translational Epidemiology Unit. Dr. Warner has a bachelor's degree from Duke University and a master's in public health (MPH) from the Yale School of Public Health. Dr. Warner completed her doctorate and the Alonzo Smythe Yerby Postdoctoral Fellowship, both in Epidemiology, at the Harvard T.H. Chan School of Public Health. Her research studies how lifestyle, behavioral, and genetic factors affect cancer screening and intermediate markers of cancer risk, cancer risk and survival, with a particular interest in molecular subtypes and racial/ethnic and socioeconomic health disparities. Dr. Warner is a member of the steering committee of the Boston Breast Cancer Equity Coalition, Research Director for the Boston Mammography Cohort Study, and Project Director for the National Consortium on Psychosocial Stress, Spirituality, and Health. She is a 2018 winner of the Dean's Community Service Award from the Office for Diversity Inclusion and Community Partnership at Harvard Medical School, and was recently named a Diversity Scholar by the Nutrition Obesity Research Center at Harvard. In addition to the Mass General Physician/Scientist Development Award, Dr. Warner’s research is funded by the National Cancer Institute.

Abstract: Impact of a Comprehensive Patient Navigation Intervention on Endocrine Therapy Adherence and Persistence among Vulnerable Women in Boston

Adherence to hormonal therapy (HT) among women with hormone receptor positive breast cancer (HR+) is suboptimal, contributing to preventable deaths and health disparities. American Society of Clinical Oncology practice guidelines recommend that women with HR+ breast cancer complete at least five, and up to 10, years of adjuvant tamoxifen and/or aromatase inhibitor therapy, depending on menopausal status. Data suggest that up to 50% of women do not complete five years of endocrine therapy, and this may be even worse among lower-income and minority women and may contribute to persistent racial and socioeconomic disparities in breast cancer survival. Previous interventions to address gaps in HT initiation, adherence and persistence have focused on education and cognitive behavioral training among patients, with limited success. However, a small but growing body of evidence demonstrates system-level interventions that may be effective. In this proposal, we build on a city-wide implementation trial to improve care to vulnerable women across Boston. Translating Research into Practice (TRIP) is a three-pronged city-wide patient navigation intervention targeted at breast cancer patients who are at risk for delays in care due to their race/ethnicity, language, or insurance status. We propose to:

  1. Determine the feasibility and validity of an online medication database compared to EMR data abstraction to measure HT adherence and persistence
  2. Evaluate the impact of TRIP on HT early discontinuation and adherence among 342 intervention patients and 263 historic controls with HR+ breast cancer

Oladapo Yeku, MD, PhD, FACP

Oladapo O. Yeku, MD, PhD, FACP
Department of Medicine, Cancer Center
Assistant Clinical Attending, Massachusetts General Hospital
Instructor of Medicine, Harvard Medical School

Dr. Yeku is an Instructor of Medicine at Harvard Medical School and an Attending Physician in Medical Oncology at the Mass General Cancer Center. He is a member of the Termeer Phase 1 therapeutics group and a member of the Mass General cellular therapy working group. He is a fellow of the American College of Physicians. Dr. Yeku completed his combined MD, PhD program at Stony Brook University School and Medicine and his Internal Medicine training at the University of Pittsburgh Medical Center. His Medical Oncology Fellowship training was at Memorial Sloan Kettering Cancer Center. Dr. Yeku’s PhD is in molecular and cellular pharmacology, and he received postdoctoral training in immunotherapy and adoptive cellular therapy. His expertise includes standard systemic treatment options, immunotherapy, targeted therapy, and immunotherapeutic modalities for Gynecologic cancers.

Abstract: Bispecific T-cell Engager (BiTE) Immunotherapy for Ovarian Cancer

Despite initially effective chemotherapy for ovarian cancer, around two-thirds of patients diagnosed will succumb to this disease. As such, novel efficacious treatments are critically needed. The presence of MUC16 (CA-125 antigen) on the surface of most epithelial ovarian cancer cells provides an opportunity for immunotherapy-based approaches that target this cancer. This project aims to exploit the MUC16 antigen via the design and testing of bispecific engager T cell molecules that bind to the cancer cell and recruit the patient’s immune system to destroy the tumor. In addition, we aim to understand the role of unfavorable elements of the tumor microenvironment and engineer countermeasures to improve the clinical efficacy of bispecific engagers. We will rationally combine other chemotherapeutics, and immunotherapeutic modalities with bispecific engagers to promote a comprehensive immune attack against cancer.

2018

J. Sawalla Guseh, MDJ. Sawalla Guseh, MD
Department of Medicine, Cardiology Division 
MGH Cardiovascular Research Center
Director, Cardiovascular Performance Program Fellowship
Instructor in Medicine, Harvard Medical School

Dr. Guseh obtained his MD from Harvard Medical School. He completed Internal Medicine Residency and Chief Residency at Massachusetts General Hospital and completed his Cardiology and Sports Cardiology training at Massachusetts General Hospital. He is a member of the cardiology division and fellowship director for the MGH Cardiovascular Performance Program. His clinical interests focus on the cardiovascular care of competitive and recreationally active individuals. His research explores the molecular biology of exercise on the heart. He has a special interest in understanding how exercise serves to reprogram, rejuvenate and reshape heart musculature with an eye to therapeutically apply this understanding to disease states like heart failure. Honors awards include the Roman W. DeSanctis Clinical Scholar Award, the American Heart Association Laennec Young Clinician Award, and the Harvard Medical School John S. LaDue Memorial Fellowship. He is the inaugural Frisbie Family Scholar and his work is currently funded by the American Heart Association, the Harold Amos Medical Faculty Development Program and the MGH Physician-Scientist Development Program.

Lay Abstract: Finding Therapeutic Ways to Shrink Enlarged and Misshapen Hearts

Six million Americans suffer from heart failure and the prevalence is expected to increase 46% by 2030. Increased heart size (cardiac hypertrophy) commonly precedes heart failure. Indeed, clinical studies show that even partial regression of hypertrophy improves major clinical outcomes. We understand little about how to mechanistically promote beneficial cardiac size normalization (or regression) and hypothesize is that there are adaptive and maladaptive regression states that conceptually parallel the adaptive physiological and maladaptive pathological growth states of cardiac hypertrophy. We are using extreme models to gain new insights into the process of cardiac remodeling. In the Burmese python, the heart undergoes repeated regression episodes after feeding. We anticipate that identification of pathways promoting beneficial regression rather than maladaptive atrophy will provide new biological insights as well as novel therapeutic targets against heart failure. We will identify transcriptional signatures of regression using multiple models that include the Burmese Python and mammalian models. We focus on a class of molecules known as microRNA because they are known key regulators of cardiac development and disease; have been largely unexplored in this context; are highly conserved across species; and are amenable to therapeutic targeting.

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Camille E. Powe MDCamille E. Powe MD
Department of Medicine, Endocrine Division, Diabetes Unit
Co-Director, Massachusetts General Hospital Diabetes in Pregnancy Program 
Assistant Professor of Medicine, Harvard Medical School

Dr. Powe is a physician-investigator in the Diabetes Unit. She received a bachelor’s degree cum laude in Anthropology from Harvard College and an MD degree magna cum laude from Harvard Medical School. Dr. Powe trained in Internal Medicine at Brigham and Women’s Hospital, where she also served as Chief Medical Resident. She then completed an Endocrinology fellowship at Massachusetts General Hospital. Her clinical practice focuses on diabetes, thyroid disease, and other endocrine problems during pregnancy; she is the Co-Director of the MGH Diabetes in Pregnancy Program. Her research focuses on the genetics and physiology of glucose metabolism in pregnancy. As such, she is the PI the Study of Pregnancy Regulation of Insulin and Glucose (SPRING), a longitudinal investigation gestational glycemic physiology. She is also the current PI of the MGH Obstetrical Maternal Study (MOMS), a large clinical and sample biobank being used to study medical disorders in pregnancy and the effects of pregnancy complications on women's health. In addition to the Massachusetts General Hospital Physician-Scientist Development Award, Dr. Powe’s research is funded by the NIH/NIDDK and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program.

Abstract: A Precision Approach to Gestational Diabetes Mellitus: Characterizing Genetic and Physiologic Subtypes

Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with an increased risk of adverse perinatal outcomes and future maternal type 2 diabetes (T2D). Randomized trials demonstrate that GDM treatment reduces the risk of complications, yet standard GDM treatment is burdensome and crude, relying on frequent blood glucose self-monitoring and trial-and-error (as glycemic responses to both diet and pharmacotherapy, prescribed when dietary treatment fails, vary greatly between individuals). GDM, until now, has been treated as one disease, but we recently demonstrated that all GDM is not the same: genetics and pregnancy outcomes differ according to the predominant late pregnancy physiologic defect leading to hyperglycemia. The goal of this project is to define and characterize GDM subtypes using physiology and genetics to develop novel personalized approaches for this increasingly common condition. We will link samples from women with prior GDM in the MGH Obstetrical Maternal Study and the Partners Biobank to clinical data from their GDM-affected pregnancies. We will test whether GDM subtypes, defined based on physiology or genetics differ in their risk for adverse perinatal outcomes, dietary treatment failure, and future maternal T2D. Our work will set the stage for novel precision approaches to the treatment of hyperglycemia and prevention of T2D in women with GDM.

2017

Aaron Aguirre, MD, PhD

Aaron Aguirre, MD, PhD
Department of Medicine, Cardiology Division
Department of Medicine, Cardiology Division Center for Systems Biology
Assistant Professor of Medicine, Harvard Medical School

Dr. Aguirre is a cardiologist and physician/scientist in the MGH Cardiology Division, the Wellman Center for Photomedicine, and the Center for Systems Biology. He received a BSE in Electrical Engineering from the University of Michigan, an SM in Electrical Engineering from the Massachusetts Institute of Technology (MIT), and a PhD in Electrical and Medical Engineering from the Harvard-MIT Division of Health Sciences and Technology (HST). He also received his MD from HST and Harvard Medical School. His graduate research was in the areas of ultrafast optics and biomedical imaging, with a focus on new methods for endoscopic optical coherence tomography. He subsequently completed clinical training and board certification in cardiology and critical care at the Brigham and Women’s Hospital and a post-doctoral research fellowship in cardiovascular imaging and biology at the MGH Center for Systems Biology before joining the faculty at MGH in 2015. Dr. Aguirre’s clinical practice concentrates on intensive care cardiology, and he is also a clinical affiliate at the MGH Healthcare Transformation Lab. His laboratory research utilizes advanced imaging and microscopy techniques to investigate the biology of ischemic heart disease and heart failure, and he is a 2014 recipient of the Fellow-to-Faculty Transition Award from the American Heart Association. The laboratory is currently funded by multiple grants from the National Institutes of Health.

Abstract: Morphology and dynamic functions of pericytes in the heart

Conditions such as heart attack and heart failure are conventionally regarded as diseases of the heart muscle. There is profound scientific interest and study of the many other cell types in the heart that interact with the heart muscle and can contribute to heart disease. Pericytes are unique cells that line the outer walls of the smallest blood vessels in the heart and are thought to have many roles in regulating blood flow and maintaining the local health of the tissue. The organization and many functions of these cells are not well understood, however, in part due to a lack of scientific tools to measure them in their native environment. This project seeks to utilize state-of-the art optical microscopy techniques and transgenic reporter mice to profile the structure and dynamic physiology of pericytes in the living, beating heart in a model of myocardial infarction or heart attack. The ultimate goal is to better understand the ways that these cells contribute to ischemic heart disease in order to develop improved pharmacologic therapies.


Fatima Cody Stanford, MD, MPH, MPA, FAAP, FACP, FAHA, FTOSFatima Cody Stanford, MD, MPH, MPA, FAAP, FACP, FAHA, FTOS
Obesity Medicine Physician for Adults, Adolescents, and Children at the MGH Weight Center
Nutrition Obesity Research Center at Harvard (NORCH) Director of Diversity
Director of External Consultative Care, MGH Weight Center
Affiliated Faculty, MGH Mongan Institute of Health Policy 
Leadership Team, MGH Midlife Women’s Health Center
Assistant Professor in Medicine and Pediatrics, Harvard Medical School

Dr. Stanford is an obesity medicine physician at Massachusetts General Hospital (MGH)/Harvard Medical School (HMS). She completed her Obesity Medicine & Nutrition Fellowship at MGH/HMS. Dr. Stanford received her BS and MPH from Emory University as an MLK Scholar, her MD from the Medical College of Georgia School of Medicine as a Stoney Scholar, and her MPA from the Harvard Kennedy School of Government as a Zuckerman Fellow in the Harvard Center for Public Leadership. Dr. Stanford completed her internal medicine and pediatrics residency at the University of South Carolina School of Medicine/Palmetto Health where she served as chief resident. She has served as a health communications fellow at the Centers for Disease Control and Prevention and as a behavioral sciences intern at the American Cancer Society. Upon completion of her MPH, she received the Gold Congressional Award, the highest honor that Congress bestows upon America’s youth. Dr. Stanford has completed a medicine and media internship at the Discovery Channel. An American Medical Association (AMA) Foundation Leadership Award recipient in 2005, an AMA Paul Ambrose Award for national leadership among resident physicians in 2009, she was selected for the AMA Inspirational Physician Award in 2015. The American College of Physicians (ACP) selected her as the 2013 recipient of the Joseph E. Johnson Leadership Award and the Massachusetts ACP selected her for the Young Leadership Award in 2015. She is the 2017 recipient of the Harvard Medical School Amos Diversity Award and Massachusetts Medical Society Award for Women’s Health. In 2019, she was selected for the Massachusetts Medical Society Suffolk Community Clinician of the Year and Reducing Health Disparities award. In 2020, she was elected as the American Medical Association Chair of the Minority Affairs Section, and she was selected as one of the inaugural recipients of the MGH Anne Klibanski Visiting Scholar Award.

Abstract: Exploring Referral Patterns and Shared Decision-Making Regarding Weight Loss Surgery in Adolescents and Young Adults with Moderate to Severe Obesity

Obesity rates continue to rise in adolescents and young adults in the US. To date, weight loss surgery is the most effective tool to treat moderate to severe obesity and its associated co-morbidities. This proposal seeks to understand predictors of referrals to tertiary weight management and subsequent weight loss surgery in adolescents and young adults. We will assess shared decision-making surrounding weight loss surgery and develop a decision aid (DA) to help adolescents and young adults with moderate to severe obesity decide if weight loss surgery might be a useful tool to treat their obesity.

2016

Nwamaka Eneanya, MD, MPH
Department of Medicine, Nephrology Division
Instructor in Medicine, Harvard Medical School


David Perez, MD, MMScDavid Perez, MD, MMSc
Departments of Neurology and Psychiatry
Director, Functional Neurological Disorders Clinic & Research Group 
Assistant Professor in Neurology, Harvard Medical School

Dr. Perez, MD, MMSc is a dual-trained neurologist-psychiatrist, cognitive-affective neuroscientist and neuroimaging researcher. Dr. Perez majored in Neuroscience and Behavior and graduated cum laude from Columbia University. He subsequently graduated from New York University School of Medicine as a member of the Alpha Omega Alpha society. Dr. Perez completed the Partners Neurology Residency program in 2011 and the Harvard Longwood Psychiatry Residency Training Program in 2014. He also obtained a Master’s of Science in Clinical and Translational Investigation from Harvard Medical School in 2016. As a faculty member in the Departments of Neurology and Psychiatry at MGH, Dr. Perez has developed a new interdisciplinary clinical program for the diagnostic evaluation and management of patients with Motor Functional Neurological Disorders. In parallel, he has established a neuroimaging research program investigating biomarkers of symptom severity, disease-risk and prognosis in Functional Neurological Disorders. In these settings, Dr. Perez is the Director of the MGH Functional Neurological Disorders Clinic within the Cognitive Behavioral Neurology Unit, and the Director of the Functional Neurology Research Group. For his efforts, Dr. Perez has been recognized by the American Neuropsychiatric Association with the 2012 Young Investigator Award and the 2014 Career Development Award.

Abstract: Neuroimaging Biomarkers of Symptom Severity, Disease Subtype and Prognosis in Functional Neurological Disorders

Motor Functional Neurological Disorders (a.k.a. Conversion Disorders) are highly prevalent and disabling neuropsychiatric disorders, comprising 16% of outpatient neurology referrals; this includes patients with Psychogenic Nonepileptic Seizures, Functional Movement Disorders and Functional Limb Weakness. Motor Functional Neurological Disorders and other medically unexplained symptoms are exceedingly costly to the U.S. health care system, with an estimated $256 billion/year spent in caring for medically unexplained illness. To date, very little is known about the underlying biological mechanisms of this disorder at the intersection of Neurology and Psychiatry. This study seeks to identify structural and functional magnetic resonance imaging biomarkers of symptom severity, disease-subtype and prognosis across the spectrum of motor Functional Neurological Disorders. The aim of this research is to advance our pathophysiologic understanding of this condition and subsequently catalyze the development of biologically informed treatment studies. It is hypothesized that structural and functional circuit changes in specific brain regions that mediate the convergence of emotional, viscero-somatic, cognitive and motor functions are associated with symptom severity, disease-subtype and prognosis in motor Functional Neurological Disorders. This research leverages a large and relatively unique patient cohort in the newly established Functional Neurological Disorders Clinic at the Massachusetts General Hospital in the Department of Neurology.


Yakeel Quiroz, PhDYakeel Quiroz, PhD
Departments of Psychiatry and Neurology 
Director, Familial Dementia Neuroimaging Lab
Co-Director, Multicultural Neuropsychology Program 
Assistant Professor, Harvard Medical School

Dr. Quiroz joined the Harvard Medical School faculty in the Departments of Psychiatry and Neurology at Massachusetts General Hospital in January 2015. She completed her PhD training in clinical psychology at Boston University and a postdoctoral fellowship in neuropsychology at MGH/Harvard Medical School.

By applying her efforts to a large family that carries a genetic mutation that causes early-onset Alzheimer’s disease (AD), Dr. Quiroz’s research has focused on characterizing brain changes that may predispose individuals to develop memory loss or dementia later in life. Her work has already provided evidence of brain abnormalities in cognitively-intact individuals at high risk for AD decades before their clinical onset. Her findings have helped the field to re-conceptualize Alzheimer as a sequence of changes that begins decades before cognitive decline, and which may be targeted by promising disease-slowing treatments at a time in which they might have their most profound effect.

Dr. Quiroz is also the co-director of the MGH Multicultural Neuropsychology Program (MUNDOS), and has strong clinical interests in the cognitive assessment of monolingual and bilingual Spanish-speaking patients.

Abstract: Tracking Tau Pathology in Familial Alzheimer’s Disease

For the first time since Alzheimer’s disease (AD) was discovered, amyloid-modifying treatments are being evaluated in clinical trials, while other disease-modifying treatments, including anti-tau antibodies, are in preclinical development. These holds promise to modify the course of AD, and even prevent its clinical manifestation if administered early enough.

We will work with an extraordinary family of approximately 5,000 individuals in Antioquia, Colombia, which contains roughly 1,800 carriers of the autosomal-dominant presenilin1 (PSEN1) E280A mutation. These carriers are virtually certain to develop AD, and have a well-characterized disease course, with dementia occurring at a mean age of 51. We are currently using cross-sectional data to characterize associations of preclinical biomarker changes with age and temporal distance to the kindred’s mean age of clinical onset. The addition of the longitudinal data proposed for this PSDA will greatly improve our understanding of the trajectory of these biomarker changes in preclinical AD and their role in subsequent cognitive decline.

2015

Martin Aryee, PhDMartin Aryee, PhD
Department of Pathology
Assistant Professor of Pathology, Harvard Medical School
Secondary Affiliations:
Associate Member, Broad Institute
Assistant Professor in the Department of Biostatistics, Harvard T.H. Chan School of Public Health

Dr. Aryee received his PhD in Biostatistics from the Harvard School of Public Health in 2008, and completed a post-doctoral fellowship at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. He joined the Massachusetts General Hospital and Harvard Medical School (HMS) Departments of Pathology as an Assistant Professor in 2012. He is an Associate Member of the Broad Institute, and holds a secondary appointment as an Assistant Professor in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health, where he teaches an introductory course on statistical genetics. Dr. Aryee’s lab develops statistical methods for the analysis of genomic and epigenomic data, with a primary interest in cancer. His research is focused on improving our understanding of how the many different cell types present in a tumor interact with each other, contributing to drug resistance and disease progression.

Abstract: Spatial statistics methods for the study of intra-tumoral heterogeneity

2013

Cesar M. Castro, MD, MMScCesar M. Castro, MD, MMSc
Department of Medicine, Medical Gynecology Oncology 
Director, Cancer Program, MGH Center for Systems Biology
Assistant Professor of Medicine, Harvard Medical School

Dr. Castro, MD, MMSc is an Assistant Professor of Medicine at Harvard Medical School and Attending Physician in Medical Gynecology Oncology at the MGH Cancer Center. Dr. Castro is a translational oncologist with experience leveraging nanotechnology and molecular imaging for solid tumor detection and serial profiling. He has served as Chair of the In Vitro Diagnostics Working Group within the NCI Alliance for Nanotechnology in Cancer. He currently directs the Cancer Program within the MGH Center for Systems Biology. Dr. Castro graduated from the University of California, Berkeley where he received both a BA in Psychology and MSc in Health and Medical Sciences. He received his medical degree from UCSF School of Medicine where he also completed his Internal Medicine residency training. Dr. Castro completed an adult oncology fellowship from the Dana-Farber / Partners Cancer Care program. During this period, he also received a MMSc in Clinical Investigation from Harvard Medical School.

Abstract: Leveraging Nanosensor Technologies for Pathway Characterization of Solid Tumors

This four-year project proposal seeks to build upon my experience with nanomedicine and published work using novel nanosensing technologies developed at MGH to profile cancer protein markers across the spectrum of human specimens: fine needle aspirates (FNAs), ascites, and peripheral blood.The project intends to optimize and translate validated micro- nuclear magnetic resonance (µNMR) into patient-oriented research efforts. Specifically, µNMR will be explored as a practical strategy for robustly quantitating 1) baseline signal transduction pathway activity; and 2) drug modulation of the targeted pathway in FNAs attained from subjects treated with one or more targeted drug therapies. Since conventional protein testing is limited by the amount of tissue procured, µNMR works within these limitations by extracting more information from an FNA – which yields fewer cells but is a less morbid procedure than excisional or core biopsies. Implementing

a tactic that could potentially 1) provide clinical investigators with same visit readouts of pathway activity; and 2) enable drug combination trials in patients with inadequate pathway inhibition to monotherapies, could improve subject selection and streamline the drug testing process.The proposed project will focus on the biologically important and therapeutically relevant PI3K-Akt and Raf-MEK-ERK pathways. If successful, µNMR could be positioned as a companion tool for use with the growing number of targeted therapy studies at MGH and beyond.

2011

Oluwaseun Johnson-Akeju, MD, MMScOluwaseun Johnson-Akeju, MD, MMSc
Anesthetist-In-Chief, Massachusetts General Hospital
Henry Isaiah Dorr Chair of Research and Teaching in Anaesthetics and Anaesthesia, Harvard Medical School

Dr. Johnson-Akeju is the anesthetist-in-chief at the Massachusetts General Hospital. He completed his undergraduate degree in biology at the New Jersey Institute of Technology and his medical degree at the New Jersey Medical School. This was followed by residency training in anesthesiology at the Massachusetts General Hospital, post-doctoral research training at Harvard University, and a faculty position at the Massachusetts General Hospital. He also holds a master’s in medical science degree in clinical investigation from Harvard Medical School.

Abstract: Identifying the Neural Circuit Mechanisms Implicated in General Anesthesia-induced Brain States

General anesthesia is drug-induced reversible neurophysiological phenomenon comprised of five distinct behavioral states: hypnosis (loss of consciousness), amnesia (loss of memory), analgesia (loss of pain sensation), akinesia (immobility), and the maintenance of physiological stability. Over 100,000 patients receive general anesthesia in the United States each day for surgical and diagnostic procedures. Despite its widespread use, the neural-circuit mechanisms by which anesthetic drugs induce the state of general anesthesia are not well understood. By studying anesthesia-induced unconsciousness and recovery of consciousness in controlled human experiments with high-density electroencephalography, and simultaneous positron emission tomography/functional magnetic resonance imaging, we are identifying the neural circuit mechanisms implicated in general anesthesia-induced brain states. This understanding has direct implications for a precise neurophysiological definition of anesthetic brain states, improved brain function monitoring, and risk stratification of patients.

2010

Richelle Charles, MDRichelle Charles, MD
Department of Medicine, Division of Infectious Diseases
Assistant Professor of Medicine, Harvard Medical School

Dr. Charles received her BS degree from the University of Maryland, College Park and her MD degree from the Johns Hopkins University School of Medicine. She completed her residency in internal medicine at the Massachusetts General Hospital in 2006, and in 2009 completed the clinical infectious disease fellowship in the Infectious Disease Fellowship training program of the Massachusetts General Hospital and the Brigham and Women’s Hospital. Her research is focused on evaluating host-pathogen interactions during human infection by V. cholerae (the cause of cholera) and Salmonella enterica serovar Typhi (the cause of typhoid fever) using high throughput proteomic and genomic technologies. She is currently an Assistant Professor of Medicine at Harvard Medical School and on faculty in the Division of Infectious Diseases, Mass General.

Abstract: Application of High-throughput Proteomics to the Study of Protective Immunity in Human Cholera Infection

The project funded by the award was focused on the application of immuno-proteomics to the study of protective immunity in human cholera infection, an infection that remains endemic in over 50 countries. An estimated 3-5 million individuals develop cholera each year, resulting in approximately 100,000 deaths. Although cholera vaccines do induce a protective immune response, immunity is short-lived, lasting approximately 6-24 months. In comparison, natural infection with cholera results in protective immunity that lasts years or decades. The mediators of this protective immune response to cholera are poorly understood. In this project, Dr. Charles used a high-throughput protein-based platform to characterize serum and mucosal anti-V. cholerae immune responses in cholera patients and vaccinees. The results of these studies have provided important insights into protective immunity of human cholera infection, and could lead to improved vaccination strategies against cholera.


Abner Louissaint, Jr., MD, PhDAbner Louissaint, Jr., MD, PhD
Assistant in Pathology, Department of Pathology
Assistant Professor of Pathology, Harvard Medical School

Dr. Louissaint, Jr. graduated in 1997 from Washington University in St. Louis as a John B. Ervin Scholar with concentrations in Biology and English literature. He received his MD from Weill Cornell Graduate School in 2005 and a PhD in Neuroscience from Weill Graduate School, where he was awarded the Julian Rachelle Award for the best original research paper published by a graduate student.

Dr. Louissaint came to Mass General in 2005, where he completed residency in Anatomic and Clinical Pathology and subsequently completed a fellowship in Hematopathology in 2010. He joined the faculty of Mass General Pathology three years ago, where his clinical expertise includes hematopathology and autopsy pathology. Dr. Louissaint is interested in the molecular genetics of lymphoma for improved prognostication and therapy.

Abstract: Molecular Genetics and Modeling of Follicular Lymphoma and Other Non-Hodgkin Lymphomas

Dr. Louissaint aims to contribute significantly to the diagnosis and treatment of lymphoma by identifying molecular alterations that help us to understand their pathogenesis, serve as prognostic indicators of outcome, and potentially represent therapeutic targets. In 2010, Dr. Louissaint was awarded an ECOR MAO physician-Scientist Development award in support of his work on follicular lymphoma. Follicular lymphoma (FL) is the second most common type of non-Hodgkin’s lymphoma (NHL). Its clinical course and prognosis are highly variable, and at present, we do not have optimal clinical or pathological prognostic indicators of outcome to assess risk and make individualized treatment choices. Therefore, there is a need to identify biological markers that can be used in practice to predict outcome and direct therapy in patients with FL.

Dr. Louissaint characterized and defined "Pediatric-Type follicular lymphoma" (PTFL), a novel type of follicular lymphoma known for its distinctly indolent course. He received the 2013 Benjamin Castleman award by the United States & Canadian Academy of Pathology. He later received the 2014 Harold Amos Medical Faculty Development Program Award by the Robert Wood Johnson Foundation and the American Society of Hematology (ASH), the 2014 Harvard Catalyst PFDD Fellowship and an American Cancer Society grant in support of his work. Dr. Louissaint defined the genetic landscape of PTFL, discovering that PTFLs harbor recurrent somatic activating mutations in MAP kinase pathway genes in almost 60% of cases. On the basis of this work and the work of others, PTFL is now defined a distinct entity in the recent 2016 WHO Classification of Hematopoietic neoplasms. Dr. Louissaint is currently using next-generation sequencing to define the genomic features of other non-Hodgkin B-cell lymphomas. To this end, he has created and leads a lymphoma repository at MGH in which lymphoma samples are viably frozen for later genetic and functional studies. Dr. Louissaint has created patient-derived models of follicular lymphoma and is currently investigating questions about the role of microenvironment in lymphomagenesis, lymphoma progression and transformation.

2007

Miguel N. Rivera, MDMiguel N. Rivera, MD
Department of Pathology
Assistant Professor of Pathology, Harvard Medical School

Dr. Rivera received an AB in Molecular Biology from Princeton University and an MD from Harvard Medical School in 2001. He completed his Anatomic Pathology residency at Brigham and Women’s Hospital and a fellowship in Molecular Diagnostics at the combined Harvard program. Dr. Rivera is now Assistant Professor of Pathology at Massachusetts General Hospital and Harvard Medical School. He is the recipient of career development awards from the Burroughs Wellcome Fund and the Howard Hughes Medical Institute. His research focuses on the use of genomic technologies to identify new pathways involved in pediatric cancer. His work has led to the discovery of the WTX tumor suppressor gene and the generation of the first chromatin state maps of Wilms tumor.

Abstract: Functional Characterization of WTX in Renal Development

Wilms tumor is the most common pediatric kidney cancer and is closely connected to kidney development. Mutations in two genes, WT1 and beta-catenin, are present in 5-10% of tumors but the genetic basis of the remaining cases is unknown. Using high resolution DNA arrays Dr. Rivera identified a new tumor suppressor gene, WTX, which is inactivated in 30% of Wilms tumors. WTX is the first example of a tumor suppressor that, due to its location on the X-chromosome, is inactivated by “single hit” events targeting the single X chromosome in males or the active X chromosome in females. During development, WTX is expressed in specialized kidney stem cells and is thus likely to have an important role in both Wilms tumor and in normal developmental processes. Dr. Rivera is now studying the function of WTX in several model systems in order to identify molecular mechanisms that are important in early kidney development and that could be widely applicable to cancer and other diseases.


Jose Florez, MDJose Florez, MD
Department of Medicine, Diabetes Unit
Chief, Endocrine Division and Diabetes Unit
Professor of Medicine, Harvard Medical School
Institute Member, Broad Institute

Dr. Florez is the Chief of the Endocrine Division and the Diabetes Unit at the MGH, where he holds the John T. Potts Jr., MD Endowed Chair in Medicine. He is also Professor of Medicine at Harvard Medical School, and an Institute Member at the Broad Institute. He and his group have contributed to the performance and analysis of high-throughput genomic studies in type 2 diabetes and related traits, in international consortia such as MAGIC, GENIE, DIAGRAM, T2D-GENES, AMP-T2D, SIGMA and RADIANT, where he plays management roles. He leads the genetics initiatives of the Diabetes Prevention Program and the GRADE clinical trial, where the effects of genetic variants on on specific behavioral and pharmacological preventive interventions can be assessed. He is the Principal Investigator of the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH), and also conducts other pharmacogenetic studies at MGH. He is an author on 190+ original publications and 50+ reviews/book chapters. In addition to his research and teaching duties, he is clinically active in the MGH Diabetes Center, the Endocrine inpatient consult service, and the MGH Down Syndrome Program. He is a recipient of the 2010 Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers. In 2019 he received the Father of the Year award from the American Diabetes Association.

Abstract: Clinical Translation of GWAS Results in Type 2 Diabetes

Genome-wide association studies (GWAS) have identified novel diabetes-associated loci with high statistical confidence. How these variants affect response to anti-diabetes medications is not known. We propose to mine recent GWAS for diabetes-associated variants in a three-pronged approach. First, we will attempt to replicate novel associations discovered in recent GWAS for type 2 diabetes and related glycemic traits in a new MGH diabetes case/control sample totaling 1,812 subjects and in the Diabetes Prevention Program (DPP), in which 2,994 participants at high risk of diabetes were randomized to a lifestyle intervention, metformin or placebo. Second, we will mine these GWAS for polymorphisms in genes that encode diabetic drug targets, and assess their effects in the DPP. And third, all high-likelihood variants will be tested in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH), and in a retrospective patient cohort treated with monotherapy culled from Partners electronic databases. With this project we hope to determine whether polymorphisms in genes that encode drug targets have an effect on diabetes risk and response to intervention.


Aaron Styer, MD
Instructor, Obstetrics, Gynecology & Reproductive Biology
Massachusetts General Hospital

2006

William Curry, MDWilliam Curry, MD
Assistant in Neurosurgery
Professor of Neurosurgery, Harvard Medical School

 

Dr. Curry is a neurosurgeon in the Stephen and Catherine Pappas Center for Neuro-oncology at Massachusetts General Hospital. Dr. Curry was born in New York, NY and studied as an undergraduate at Harvard University. He graduated from Cornell University Medical College in 1997 and completed his neurosurgery residency at Massachusetts General Hospital in 2004.

He specializes in the surgical care of patients with benign and malignant brain, skull base, and spinal tumors. His research focuses on the development and evaluation of novel therapies for brain tumors. malignant brain tumors are often associated with a dismal prognosis, and despite advances in surgical technique, radiation, and chemotherapy, few patients with glioblastoma remain alive three years after diagnosis. He is a co-Director of Mass General Neuroscience, and a Professor of Neurosurgery at Harvard Medical School.

Dr. Curry conducts translational research in immunotherapy for malignant brain tumors and is developing clinical trials involving immunotherapeutic and other biologic and cellular approaches. He works closely with Glenn Dranoff, MD at the Cancer Vaccine Center at the Dana Farber Cancer Institute Through work initially supported by the 2006 Physican/Scientist Development Award, he has designed and executed a clinical protocol for cytokine- based immunotherapy for brain tumors that combines autologous tumor cell vaccination with bystander cells expressing granulocyte-macrophage colony stimulating factor (GM-CSF) as a stimulator of cellular and humeral anti-tumor immunity. Bring the findings of this study back to the bench, Dr. Curry studies combination immunotherapy in preclinical model and he has characterized the cellular details of lymphocyte infiltration into brain tumors.. He has also served as Primary Investigator in several multi-center brain tumor immunotherapy clinical trials.

Dr. Curry is also continually engaged in research involving assessment of patient outcomes, particularly those with brain tumors. One current focus is on achieving representative ethnic diversity in cancer clinical trials and understanding ethnic variations in biological responses to therapies. He is also focused on implementing minimally invasive approaches to resecting tumor at the skull base and in the brain.

Abstract: Host Antitumor Immunity in Patients with Brain Tumors

Malignant glioma is a relentlessly progressive and universally fatal disease. Median survival is only 14 months, and there is no known effective treatment for recurrent disease. Immunotherapy represents a promising approach by which to target these intracranial tumors; however, for such therapy to be effective, we must overcome the systemic and local immunosuppression associated both with these tumors and their treatments.

They are conducting a phase I clinical study in which glioma cells are harvested from patients at surgery, irradiated, mixed with a GM-CSF – producing cell line and implanted subcutaneously in patients for a scheduled six vaccinations. measured outcomes in this study include safety, feasibility, and biological effect, including development of antitumor immunity. We are performing detailed serological analyses of antibody and T lymphocyte responses to patient brain tumors in an effort to uncover antigenic tumor epitopes and to further unravel the basic mechanisms by which the immune system responds to human brain tumors.

2005

Sherri-Ann M. Burnett-Bowie, MD, MPHSherri-Ann M. Burnett-Bowie, MD, MPH
Assistant Professor of Medicine, Harvard Medical School
Associate Director, Mass General Center for Diversity and Inclusion
Director, Multicultural Affairs, Department of Medicine, Mass General

Dr. Burnett-Bowie received her AB in Biochemical Sciences cum laude from Harvard College in 1993, MD from the University of Pittsburgh, School of Medicine in 1997, and MPH. degree from the Harvard T.H. Chan School of Public Health in 2005. She completed her residency in Internal Medicine and fellowship in Endocrinology at Massachusetts General Hospital. Dr. Burnett-Bowie holds a faculty appointment as an Assistant Professor of Medicine at Harvard Medical School. She is a staff endocrinologist in the Mass General Endocrine Unit. She serves as an Associate Director of the Mass General Center for Diversity and Inclusion; and as the Director of Multicultural Affairs for the Department of Medicine (DOM), where she co-chairs the DOM’s Diversity and Inclusion Board. In 2005, Dr. Burnett-Bowie was awarded the Mass General PSDA for a project that investigated the relationship between vitamin D deficiency and insulin resistance in humans. Her research also focuses on the epidemiology of menopause.

Abstract: The Impact of Vitamin D Deficiency on Insulin Resistance

The United States is experiencing a significant increase in the prevalence of Type 2 diabetes mellitus (T2DM). Communities of color are especially affected. Vitamin D deficiency (VDD), also more prevalent in minority populations, appears to contribute to insulin resistance (IR). However, no large clinical trials of the impact of treating VDD on IR exist. We hypothesized that treatment of VDD would decrease IR. We randomized 90 vitamin D deficient (25-OHD < 20 ng/mL), healthy men and women of diverse racial background to vitamin D 50,000 international units, or placebo, QWK for 12 weeks. The primary endpoint was the change in IR as assessed by modified IVGTT. While we observed the previously reported negative association between insulin resistance and vitamin D levels, repletion of vitamin D deficiency over 12 weeks did not change insulin secretion or resistance in any subjects (Mitchell et al, American Journal of Clinical Nutrition 2015; 102: 1-8). It will be important to follow-up these results with longer term interventional studies that include glucose tolerant and intolerant subjects. However, these findings suggest that there is not a benefit to repleting vitamin D deficiency from an insulin resistance perspective.