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“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 PSDA
J. Sawalla Guseh, MDDepartment of Medicine, Cardiology Division MGH Cardiovascular Research Center Clinical and Research Fellow, Harvard Medical School
Dr. Guseh is a clinical and research fellow in the Massachusetts General Hospital (MGH) Cardiology Division and is a post-doctoral fellow in the Rosenzweig laboratory within the MGH Center for Cardiovascular Research (CVRC). Dr. Guseh received his bachelor’s degree in Biochemical Sciences from Harvard University (Cambridge) and completed his medical degree (M.D.) at Harvard Medical School (Boston). He completed residency training in internal medicine at MGH where he also served as Medical Chief Resident from 2016 - 2017. As a cardiovascular medicine fellow at MGH he has pursued additional training in sports cardiology within the Cardiovascular Performance Program. His research utilizes physiological models and sequencing-based tools to investigate the biology of cardiac remodeling. He is a recipient of the Roman DeSanctis Clinical Scholar Award, the Mort Swartz Humanism Award, and the John S. LaDue Memorial Fellowship for Cardiovascular Research at Harvard Medical School. Dr. Guseh will transition to staff as an attending cardiologist in the summer of 2019.
Abstract: Evaluation of functional microRNA regulators of cardiac regression and atrophy
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. 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 pathology; have been largely unexplored in this context; are highly conserved across species; and are amenable to therapeutic targeting. We will systematically investigate candidate miRs for functional effects associated with cardiac regression employing well-established in vitro cardiomyocyte models to prioritize for in vivo functional assessment.
Camille E. Powe MD Department of Medicine, Endocrine Division, Diabetes Unit Co-Director, Massachusetts General Hospital Diabetes in Pregnancy Program Instructor in 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.
Aaron Aguirre, MD, PhDDepartment of Medicine, Cardiology Division Department of Medicine, Cardiology Division Center for Systems BiologyAssistant Professor of Medicine, Harvard Medical School
is a cardiologist and physician/scientist in the MGH Cardiology Division and the MGH 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 endoscopicoptical 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.
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
Obesity Medicine Physician for Adults, Adolescents, and Children at the MGH Weight Center Affiliated Faculty, MGH Mongan Institute of Health PolicyAssociate, Disparities Solution CenterExecutive Committee, Nutrition Obesity Research Center at Harvard (NORCH) Leadership Team, MGH Midlife Women’s Health CenterInstructor 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 a 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 2018, she was selected for the Albert Nelson Marquis Lifetime Achievement Award and for Who’s Who in the World.
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.
Nwamaka Eneanya,MD, MPH Department of Medicine, Nephrology DivisionInstructor in Medicine, Harvard Medical School
Dr. Nwamaka Eneanya received a bachelor’s degree in Sociology from Cornell University, medical degree from Meharry Medical College, and master’s degree in public health from Harvard T.H. Chan School of Public Health. In 2011, she completed her residency training in internal medicine at Brigham and Women’s Hospital followed by nephrology training at the Massachusetts General Hospital/Brigham and Women’s Hospital Combined Nephrology Fellowship program. Dr. Eneanya has served as an Assistant in Medicine in the MGH Nephrology Division and Instructor in Medicine at Harvard Medical School since 2014. Her clinical and research interests include informed treatment decision-making, end-of-life care, and racial disparities among patients with advanced kidney disease. Dr. Eneanya was the inaugural recipient of the Sharon Anderson Research Fellowship Award through the American Society of Nephrology Foundation for Kidney Research in 2013 and is also currently supported by the Loan Repayment Program through the National Institute on Minority Health and Health Disparities at the National Institutes of Health. She serves on the steering committee of the National Coalition for Supportive Care of Kidney Patients and is dedicated to improving patient-centered care for patients with kidney disease.
Abstract: Integrating Advance Care Planning Into a Pre-Dialysis Educational Program
Patients with end-stage kidney disease (ESRD) experience higher mortality and more aggressive end-of-life (EOL) care compared to other seriously ill patient populations. In light of this data, recent evidence has demonstrated the value of patient-centered care and aligning treatment with patient preferences and goals. Pre-dialysis education programs are the standard of care for patients with advanced chronic kidney disease (CKD) who have progressed to ESRD to learn about treatment options. However, these programs do not routinely incorporate advance care planning (ACP), the process of discussing and documenting preferences for care at the end of life. Effective ACP results in greater patient and family satisfaction with care, greater hospice utilization, and lower rates of in-hospital death. The goals of this work will be to 1) develop an ACP educational intervention that will be integrated into a standard pre-dialysis program and 2) evaluate its preliminary efficacy on increased use of ACP among patients with advanced CKD and their families. This study will provide invaluable data to create a comprehensive pre-dialysis educational program to improve EOL education and informed decision-making for patients with kidney disease.
David Perez, MD, MMSc Departments of Neurology and PsychiatryDirector, Functional Neurological Disorders Clinic & Research Group Assistant Professor in Neurology, Harvard Medical School
Dr. David L. Perez is a dua-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, PhDDepartments of Psychiatry and Neurology Director, Familial Dementia Neuroimaging LabCo-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.
Martin Aryee, PhDDepartment 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. Martin Aryeereceived 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
It is increasingly clear that there can be significant genetic and epigenetic variability within a single tumor in a single patient. This intra-tumor heterogeneity has implications both for understanding the biology of tumor development, and for effective patient management since clinical decisions are based on pathological diagnosis of a small biopsy that may not represent the entirety of the tumor. While pathologists have long recognized morphological variability within tumors, high-throughput molecular techniques have until recently been limited to bulk ‘averaged’ tissue measurements, which obscure cell-to-cell variability. We are working in collaboration with labs that are developing techniques for in- situ genomic profiling of biomolecules including RNA and protein. These approaches will allow the simultaneous study of changes in tissue architecture and cell state in diseases such as cancer. While proof-of-principle experiments have demonstrated the feasibility of in-situ transcriptional profiling, adoption of the techniques will be hampered by the lack of established bioinformatics tools. We plan to develop a publicly available computational analysis tool set for spatially resolved genomics data. These data can be layered on top of traditional morphology-based pathology images to dramatically improve our ability to characterize cellular states and diversity in tumors and other tissues.
Opeyemi Olabisi, MD, PhD Department of Medicine, Nephrology Division Instructor in Medicine, Harvard Medical School
Dr. Olabisi graduated in 2001 from The City College of New York with a bachelor’s degree in Biology. He received his MD, PhD degree in 2009 from Albert Einstein College of Medicine where he studied the regulation of the transcription factor, NFAT. He came to MGH in 2009, completed residency in internal medicine, and subsequently completed a fellowship in the combined MGH-BWH nephrology fellowship program. Dr. Olabisi recognizes that an effective approach to reducing the mortality associated with chronic kidney disease (CKD) is to reduce the rate of progression of CKD to end stage kidney disease (ESKD). This passion motivates his ongoing research of the mechanism by which mutations in ApoL1 gene accelerate progression of CKD to ESKD. Early in 2015, he joined the Faculty of Renal Division in MGH Department of Medicine. In support of his work, Dr. Olabisi recently received the 2015 Harold Amos Medical Faculty Development Award from the Robert Wood Johnson Foundation.
Abstract: Unmasking the Molecular Mechanism of ApoL1 Nephropathy
Though African Americans represent 13% of U.S. population, more than 32% of patients on dialysis in the U.S. are African Americans. The incidence of end stage kidney disease (ESKD) among African Americans is 5 times that of European Americans. Two common coding mutations in apolipoprotein L1 (ApoL1) gene found almost exclusive in people of recent African origin account for most of this excess risk of ESKD. However, the mechanism by which these mutant ApoL1 cause kidney disease remains unknown. Dr. Olabisi’s research is focused on uncovering the molecular mechanism by which mutant ApoL1 proteins cause kidney disease.
Aimalohi Ahonkhai MD, MPH Assistant in Medicine, Division of Infectious Disease Instructor in Medicine, Harvard Medical School
Dr. Aimalohi Ahonkhai completed her undergraduate training in Biological Anthropology at Harvard College in 1998. It was there that she began to nurture her interest in global infectious disease. She obtained her MD from Johns Hopkins University in 2004 after spending a year conducting translational HIV research as a Doris Duke Fellow. She completed her residency in Internal Medicine at Johns Hopkins Hospital in 2007. In 2008, she obtained an MPH from Johns Hopkins/Bloomberg School of Public Health, and completed an HIV Fellowship sponsored by the HIV Medical Association. Motivated to pursue a career in clinical investigation, Dr. Ahonkhai completed training in clinical Infectious Disease at MGH/BWH in 2010. As an NIH T32-funded research fellow, she studied predictors of retention to HIV care in Southern Africa under the mentorship Dr. Kenneth Freedberg. Dr. Ahonkhai received a NIAID K23 Career Development Award in 2012. With collaborators in Nigeria, she established the Care4Life Program, a multidisciplinary, initiative to study and improve retention in HIV care. With the support of the MGH Physician Scientist Development Award, Dr. Ahonkhai will expand her study of health-system and patient-level predictors, as well as outcomes, of loss to follow-up and interruption from HIV care in Nigeria.
Abstract: Understanding Health System and Patient-Level Predictors of Unplanned Care Interruption and Loss to Follow-Up from HIV Care in Nigeria
Sub-Saharan Africa contributes a staggering 71% of the global population living with HIV. Nigeria, the most populous country in Africa, has an estimated 3.5 million people with HIV, the second largest worldwide. Despite the tremendous gains of antiretroviral therapy (ART) scale-up in Nigeria and other countries in the past decade, loss to follow-up (LTFU) and unplanned care interruption continue to undermine the clinical and transmission benefits of ART. One in four patients are lost-to-follow-up one year after initiating ART, resulting in loss of the survival gains of treatment. While some patients are completely lost from HIV care, about one-third interrupt but then return to care. Studies among this group are extremely limited. 1 Patient retention in care is likely influenced by a combination of health-system factors, driven by the facility and healthcare environment, and patient-factors, driven by individuals and community.
With support from the Physician Scientist Development Award, I aim to address important gaps in knowledge on patient retention. I have developed a collaboration with the AIDS Prevention Initiative in Nigeria (APIN), a large, multi-site HIV treatment program in Nigeria now caring for over 100,000 patients, to launch the Care4Life Study. Our team is enrolling a prospective patient cohort, which will consist of 750 patients newly enrolled in care and initiated on ART. We will investigate a range of factors informing patient decisions to remain in care over time, including clinical status, socio-demographic factors along with competing priorities on healthcare, stigma, religious/traditional beliefs, and levels of decisional conflict. I will also lead an effort to study APIN’s large retrospective database at 36 HIV treatment centers to identify health-system characteristics associated with patient retention. These studies will inform the development of novel interventions to improve retention for HIV-infected patients in Nigeria, and other resource-limited settings.
Tariro Makadzange, MD, PhD Assistant in Medicine, Division of Infectious Diseases Instructor in Medicine, Harvard Medical School
Dr. Azure Tariro Makadzange is an infectious disease physician scientist. She graduated from Harvard Medical School and received a PhD in HIV immunology from the University of Oxford. She trained in internal medicine at the University of Washington and did her Infectious Disease fellowship at Massachusetts General Hospital. Her primary research focus in on HIV infection and related opportunistic infections (OIs). She currently works focuses on understanding the immune correlates of HIV disease progression in perinatally infected children and adolescents, as well as the immunopathogenesis of cryptococcal disease in HIV infected adults. She is also involved in clinical trials and operational research studies. She recently completed a study to evaluate outcomes in children and adolescents at one of the largest public programs in Zimbabwe, and is leading a team to implement the CryptoART study in 13 clinics throughout Harare. The aim of the implementation science study is to reduce mortality among patients initiating ART through early screening and identification of those at risk of developing cryptococcal disease. She has also established a research an MGH-UZCHS collaborative research lab in Zimbabwe.
Abstract: Immunopathogenesis of Cryptococcal Reactivation in HIV infection
Cryptococcus is a fungus that affects humans and animals. It is a major opportunistic infectious agent and a leading cause of mortality in HIV-infected patients, particularly in the sub-Saharan region. Seroprevalence data suggests that >70% of individuals have acquired cryptococcal disease by age 7. Most individuals clear infection or achieve a state of disease latency. In individuals with severe immunocomprise (CD4 count <100 cells/l) cryptococcal disease can reactivate. There is limited understanding of the immune mediators of cryptococcal disease reactivation in humans. The aim of this study is to understand the cellular and humoral immune mediators associated with disease reactivation defined by positive cryptococcal antigenemia (CrAg) in HIV infected patients with low CD4+ counts. This study is a substudy nested within the CryptoART study. The CryptoART study population will be stratified into 2 main groups, those who are CrAg positive and those who are CrAg negative. A sub-cohort of individuals with cryptococcal antigenemia will be selected and age, gender and CD4 matched with individuals without antigenemia. Cryptococcal seroprevalence will be determined using ELISA to determine the IgG antibodies to glucuronoxylomannan (GXM) polysaccharide of cryptococcus. Inflammatory and suppressor cytokines IL-1, IL-6 IL-10 and IL-17 have been been shown in animal models to be critical for control of cryptococcal disease. Luminex technology will help identify inflammatory cytokines that may be important in regulating cryptococcal disease activation in humans. We will also use IFN- ELISpot assays and flow cytometry to determine the function and phenotype of antigen specific T cells to cryptococcus in those with and without evidence of disease reactivation.
Javier Irazoqui, PhD Assistant Professor of Pediatrics, Harvard Medical School Associate Immunologist, Department of Medicine
Dr. Javier Irazoqui earned his bachelor's degree at Universidad Nacional de Rosario, Argentina. He attended graduate school at Duke University Medical Center, where he obtained his PhD in Cell Biology in 2003 for his work on molecular mechanisms of cytoskeletal regulation. He joined the MGH the same year as a Jane Coffin Childs postdoctoral fellow and later a Charles King Trust Fellow, in the laboratory of Dr. Fred Ausubel in the Department of Molecular Biology. In Dr. Ausubel's laboratory, Dr. Irazoqui investigated fundamental mechanisms of innate immunity and of MRSA virulence using C. elegans genetics and genomics. In 2009, Dr. Irazoqui joined the Faculty of MassGeneral Hospital for Children as Associate Immunologist, and in 2010 the Department of Pediatrics of Harvard Medical School as Assistant Professor. In 2014 he joined the Center for the Study of Inflammatory Bowel Disease. Dr. Irazoqui's research focuses on fundamental mechanisms of host defense against infection and on host-microbiota interactions, with the ultimate goal to develop better diagnostics and treatments for bacterial infections, chronic inflammation, and metabolic syndrome.
Cesar M. Castro, MD, MMSc Department of Medicine, Medical Gynecology Oncology Director, Cancer Program, MGH Center for Systems BiologyAssistant Professor of Medicine, Harvard Medical School
Dr. Castro, 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.
Rhonda Bentley-Lewis, MD, MPH, MMSc
Department of Medicine, Diabetes UnitAssistant Professor of Medicine, Harvard Medical School
Dr. Bentley-Lewis earned her Bachelor’s degree at Harvard and Radcliffe Colleges. She went on to the University of Pennsylvania where she earned her Doctorate in Medicine at the School of Medicine and a Master’s in Business Administration at the Wharton School in healthcare management. She completed both her Internal Medicine residency and Endocrinology fellowship at Brigham and Women’s Hospital in Boston. During this time, she earned a Master’s in Medical Science from Harvard Medical School focusing on clinical investigation. She joined the Diabetes Unit at the Massachusetts General Hospital in 2010 in order to focus her clinical practice and clinical research on diabetes in pregnancy and the consequent adverse maternal outcomes. In addition to the MGH Executive Committee on Research/Multicultural Affairs Office Physician Scientist Development Award, her research efforts have been funded by the NIH/NCRR, NIH/NIDDK, and Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program Award.
Abstract: Cardiometabolic Disease Risk Subsequent to Gestational Diabetes Mellitus (GDM)
Gestational diabetes mellitus (GDM) affects approximately 7% of all pregnancies in the US and is associated with an increased risk of subsequent maternal type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Because of the increasing prevalence of GDM, particularly among non-white populations who are disproportionately impacted by the adverse cardiometabolic outcomes, an enhanced understanding of cardiometabolic disease predictors is critical to reduce the adverse maternal sequelae of GDM. The goals of my research are to elucidate potential mechanisms to underlying the unique pathological and metabolic changes that contribute to cardiometabolic disease risk in this population.
Oluwaseun Johnson-Akeju, MD, MMScAssistant in Anesthesia, Critical Care and Pain Medicine Associate Professor of Anesthesia, Harvard Medical School
Dr. Oluwaseun Johnson-Akeju is an Associate Professor of Anesthesia at Harvard Medical School, and the Director of Neuroanesthesia in the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital. He received his medical degree from Rutgers - The New Jersey Medical School in 2006. He subsequently completed his clinical training in anesthesia at the Massachusetts General Hospital, followed by post-doctoral research training at Harvard University. He also holds a Masters in Medical Science degree in clinical investigation from Harvard Medical School. His laboratory performs translational neuroscience research targeted at developing, and implementing strategies to preserve the brain health of patients.
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.
Richelle Charles, MDDepartment of Medicine, Division of Infectious Diseases Assistant Professor o
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 (MGH) 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, MGH.
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, PhDDepartment of PathologyAssistant Professor of Pathology
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 MGH 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 MGH 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: Identification of Novel Molecular Prognostic Parameters in Follicular Lymphoma
Dr. Louissaint’ s primary goal as an investigator is to contribute significantly to the diagnosis and treatment of lymphoma by identifying parameters and 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), accounting for approximately 20% of cases worldwide. 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 a novel set of pathologic parameters to identify a subtype of limited stage FL with low malignant potential in children and adults, proposing the name “Pediatric-Type follicular lymphoma” (PTFL) for this clinically unique subset of cases. For his paper on this work, he received the 2013 Benjamin Castleman award by the United States & Canadian Academy of Pathology; the award is granted for an outstanding paper published in the field of human pathology by a researcher under age 40. Subsequently, Dr. Louissaint 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. Most recently, Dr. Louissaint has defined the genetic landscape of PTFL, showing that it has a strikingly lower number of recurrent genetic aberrations than typical FL, including a near absence of epigenetic modifier gene mutations. In addition, he discovered that PTFLs harbor recurrent somatic activating mutations in MAP kinase pathway genes in almost 60% of cases, including hotspot mutations in MAP2K1 (MEK) and MAPK1 (ERK2). On the basis of this work and the work of others, PTFL is now defined a distinct entity in the recent 2016 publication of WHO Classification of Hematopoietic neoplasms. Dr. Louissaint is currently using high throughput sequencing to define the genomic features of other groups of non-Hodgkin B-cell lymphoma that have distinct clinical behavior. He is also working to create mouse models of these diseases.
Read about our previous recipients
For more information, please contact:
Elena Olson, J.D.Executive Director, Center for Diversity and InclusionMassachusetts General Hospital55 Fruit Street, BUL 123Boston, MA 02114Phone (617) 724-3831
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