Oluwaseun Johnson-Akeju, MD
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.
Department of Anesthesia, Critical Care and Pain Medicine
2011 Physician-Scientist Development Award Recipient
Christiano R. Alves, P.h.D.
Department of Neurology
Center for Genomic Medicine
Instructor in Neurology, Harvard Medical School
Dr. Alves is a junior faculty (Instructor) in the Department of Neurology and in the Center for Genomic Medicine at Massachusetts General Hospital (MGH) and Harvard Medical School. He is interested in the convergence between genome editing and applied physiology to make an impact on human health. His current research efforts focus on the development of genome editing technologies to treat neuromuscular diseases. In parallel, he is dedicating research to identifying novel biomarkers to track muscular and neuromuscular diseases. Dr. Alves holds a Ph.D. in muscle physiology from the University of Sao Paulo located in his hometown Sao Paulo, Brazil. Before joining the Kleinstiver lab at MGH, he was a postdoctoral research fellow at Joslin Diabetes Center, Harvard Medical School (2017-2018), and at the Center for Genomic Medicine, MGH (2018-2021).
Abstract: Development of in vivo base editing as a genetic treatment for spinal muscular atrophy
Spinal muscular atrophy (SMA) is a devastating neuromuscular disease and a leading genetic cause of infantile death worldwide. Despite exciting progress in the neuromuscular field that has resulted in novel therapies, there remains no permanent cure for SMA. Therefore, developing a permanent treatment that treats the underlying genetic perturbation and all systemic manifestations of this disease would transform patients’ life. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene. An important modifier of SMA severity is the number of copies of a paralogous gene SMN2. The sequence of SMN2 mainly differs from SMN1 by a C•G-to-T•A transition in exon 7 (“C6T”), which causes the skipping of exon 7 in most SMN2 transcripts due to alternative splicing. While previous studies have demonstrated that antisense oligonucleotides (ASOs) or small molecules targeted to SMN2 gene can transiently increase full-length SMN protein expression, this approach requires repeated dosing and has incomplete penetrance that poses challenges for patients. Therefore, we are developing optimized base editors (BEs) that enable precise genetic alterations within defined regions of the SMN2 gene. In this proposal, we plan to extend this work by optimizing the most optimal genome editing approaches and investigating the use of adeno-associated viruses (AAVs) to deliver these novel editing technologies in SMA mouse models. In principle, this will create a lasting single-dose permanent treatment for SMA with several advantages compared to targeting mutations in the SMN1 gene or exogenous gene replacement. The success of this proposal will provide solutions to questions at the intersection of the fields of genome editing and neurogenetics, with broad implications for the entire neuromuscular scientific community.
Pierre Ankomah, MD PhD
Department of Medicine, Division of Infectious Diseases
Instructor, Harvard Medical School
Dr. Ankomah’s research investigates microbial and host immune response dynamics in infectious syndromes. His current primary focus is using transcriptional analysis of immune cells at single-cell resolution to study the immunological heterogeneity underlying sepsis. Dr. Ankomah received his MD and PhD degrees from Emory University. He completed Internal Medicine residency at MGH and the combined Infectious Diseases fellowship training program at MGH/BWH. His work is also supported by a Harvard KL2/Catalyst Medical Research Investigator Training (CMeRIT) award. Dr. Ankomah is a recipient of the American Society for Clinical Investigation’s Emerging Generation Award in recognition of his potential as an academic physician-scientist.
Abstract: Single-cell transcriptional analysis of immune cells to investigate patient heterogeneity in sepsis
Sepsis is a common and deadly disease that causes about 11 million deaths worldwide annually. It is characterized by organ failure from dysfunctional immune responses to infection; yet the specifics of immune dysfunction are poorly understood and vary widely among different patients. Current management strategies for sepsis ignore this heterogeneity, instead relying on a “one-size-fits-all” approach to diagnostics and treatment that has been a major reason for limited progress in improving sepsis outcomes for decades.
Transcriptional analysis of cells at single-cell resolution (single-cell sequencing) is a transformative new tool to probe disease pathogenesis. Recent studies in our laboratory using this methodology have made novel findings, including identification of a new immune cell subtype enriched in sepsis. In this project, we will use single-cell sequencing to investigate the immune cell heterogeneity within a cohort of sepsis patients. These studies will evaluate immune cell abundance and transcriptional changes over time, allowing us to discover the response of each individual immune cell type to infection. Ultimately, we anticipate that this project will expand our understanding of disease mechanisms in sepsis, allow precise distinction between sepsis and its mimics, and characterize patient subtypes to identify those that may respond favorably to certain therapies.
Adjoa Anyane-Yeboa, MD, MPH
Division of Gastroenterology, Department of Medicine
Instructor of Investigation, Mongan Institute
Assistant Professor of Medicine, Harvard Medical School
Dr. Anyane-Yeboa is a gastroenterologist at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School. She received her medical degree from the University of Cincinnati, completed her internal medicine residency and a 4th year chief residency at the University of Illinois at Chicago, and completed her gastroenterology fellowship at the University of Chicago Medicine. After completing her gastroenterology training, she went on to pursue additional training to further her drive to achieve equity in health outcomes for patients from vulnerable communities. She completed the Commonwealth Fund Fellowship in Minority Health Policy through Harvard Medical School where she also received her Master’s in Public Health with a focus in Health Policy from the Harvard T.H. Chan School of Public Health.
Dr. Anyane-Yeboa’s research focuses on health equity in gastroenterology, with a specific focus on understanding IBD in minority populations and increasing colorectal cancer (CRC) screening in community health centers. Her long-term goal is to reduce inequities in CRC screening in marginalized groups using equity-driven implementation science methods. She has previously received funding from a National Cancer Institute diversity supplement, American Cancer Society, Trefler foundation and Pfizer Medical Grants Program to support her work. She is actively involved in her national gastroenterology societies and serves on the Diversity Committees for the American College of Gastroenterology and the American Gastroenterological Association. She is a prior recipient of the Rising Star Award from the University of Cincinnati Alumni Association and the University of Chicago Division of Gastroenterology Walter L Palmer Junior Alumni award.
Abstract: Initiating Colorectal Cancer Screening in Unscreened Individuals 45 to 54 Using Principles of Patient Activation
Colorectal cancer (CRC) is the third leading cause of cancer death in Black men and women, with mortality rates that are 44% and 31% higher in Black men and women compared to White men and women. Approximately 40% of the difference in incidence and 20% of the difference in mortality are due to disparities in screening. Community health centers (CHCs) in urban areas serve a large share of racial and ethnic minority patients and have lower screening rates (41.9%) compared to the general population (69.7%). Low screening rates, and rising incidence and mortality from CRC in adults at younger ages also suggests that focusing on increasing screening uptake from 45 to 54 is a critical target. The objective of this study is to use equity-driven implementation strategies to initiate CRC screening in unscreened individuals aged 45 to 54 at Codman Square Health Center (CSHC) using principles of patient activation. This award leverages an existing partnership with CSHC, a predominantly Black CHC in inner-city Boston. This proposal has three scientific aims: (1) identify system-level and patient-level determinants of CRC screening in individuals 45 to 54 using mixed methods; (2) identify equity-driven implementation strategies to initiate CRC screening matched to determinants; and (3) conduct a randomized pilot evaluation to determine impact of implementation strategies on CRC screening.
Study Design: The proposed project utilizes mixed methods and equity-driven implementation science methods to increase CRC screening in a predominantly Black CHC. To achieve this goal we will (1) identify patient and system-level determinants of CRC screening through an organizational survey and focus groups with patients and staff guided by an equity-driven CFIR framework; (2) develop implementation strategies matched to determinants using implementation roadmaps; and (3) perform a rapid cycle pilot evaluation to test implementation strategies at the patient- and system-level using an equity-driven RE-AIM framework. The combination of formal training and mentored research outlined in this application is designed to ensure that Dr. Anyane-Yeboa will emerge as a nationally recognized independent investigator with the skills and experience to reduce CRC inequities in marginalized patient populations.
Maria Agustina Battistone, PhD
Department of Medicine, Nephrology Division, MGH Program in Membrane Biology
Assistant Professor of Medicine, Harvard Medical School
Dr. Battistone have been an Assistant Professor of Medicine at Harvard Medical School (HMS) and Massachusetts General Hospital (MGH) since April 2022. Her laboratory explores the molecular basis of mucosal immunity in the urogenital tract and applies the knowledge acquired through basic research to identify new diagnostic/therapeutic targets for kidney injury and male infertility.
She obtained her bachelor’s degree in Biochemistry in 2008 at the University of Buenos Aires, Argentina. She conducted her Ph.D. studies at the same university, focused on sperm physiology. From June 2015 to July 2019, she performed her Postdoctoral training in Dr. Breton’s laboratory at MGH, and was awarded the Lalor Fellowship to study molecular mechanisms involved in luminal acidification in the urogenital tract. While examining the role of proton-secreting cells in epithelial dynamics, they uncovered a completely novel role for these cells in immune regulation she started her research group in April 2022, when her first NIH R01 was awarded. Her scientific contributions were recognized by different awards, including the DOM MGH Sanchez and Ferguson Research Faculty Award, and the MGH Claflin Distinguished Scholar. In addition, she have been involved in the training of postdoctoral fellows, international Ph.D. students, and pre-medical school students.
Abstract: Immune tolerance disruption induces kidney injury
Acute kidney injury (AKI) is an important clinical disorder affecting many patients worldwide. Given its high prevalence and mortality, AKI is currently diagnosed only after renal injury has occurred, and there is no specific cure. Therefore, there is a clear need for the development of early markers of AKI and an associated therapy to reverse/prevent this complication. The current proposal addresses this clinical gap by leveraging novel mechanisms by which epithelial proton-secreting intercalated cells (ICs) communicate damage to immunocytes in the kidney. Uncontrolled inflammation is a leading cause of AKI. Our hypothesis is that the ICs are strategically positioned to interact with immunocytes, the so-called mononuclear phagocytes (MPs), to survey the renal epithelial barrier and regulate the balance between inflammation and tolerance. In the first aim, we will elucidate the major roles of ICs together with MPs after the ablation of immunotolerance. In the second aim, we will evaluate IC - MP crosstalk to mount an anti-inflammatory response during AKI, performing renal ischemia followed by reperfusion injury. The research proposed will use an innovative multidisciplinary approach to describe how specialized epithelial cells and immunocytes communicate in the kidney. Ultimately, such knowledge will fill gaps to understand the pathogenesis of AKI.
Margarete Diaz Cuadros, PhD
Department of Molecular Biology
Instructor in Investigation
Lecturer in Genetics, Harvard Medical School
Dr. Diaz-Cuadros is an Instructor in Investigation in the Department of Molecular Biology at Massachusetts General Hospital. She earned her Bachelor’s degree from Columbia University (2014), where she worked on neural development in the nematode Caenorhabditis elegans with Dr. Martin Chalfie. She later completed her PhD under the supervision of Dr. Olivier Pourquie at Harvard Medical School (2022), where she established in vitro models of the mammalian segmentation clock based on pluripotent stem cells. Through the Junior Fellows Program hosted by the Department of Molecular Biology, Margarete was able to launch her independent research career directly after graduate school. Her research focuses on understanding the mechanisms that allow some mammalian species to complete embryonic development faster than others. For instance, a mouse embryo is formed in 15 days, but a human embryo requires 56 days to complete the same process. In the long term, the goal of this research program is to provide a basis for the acceleration of human pluripotent stem cell differentiation for disease modeling and cell-based therapies.
Abstract: Role of NADH Shuttles in Regulating Species-Specific Developmental Rates
All mammalian embryos undergo a highly conserved sequence of developmental events, but different species complete this sequence at significantly different speeds. For instance, a mouse embryo is formed in 15 days, but a human embryo requires 56 days to complete the same process. How species-specific developmental rates are set represents a major unanswered question in developmental biology. We recently established an in vitro system that recapitulates the twofold difference in developmental rate between mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we uncovered that a higher cytosolic NAD+/NADH ratio in mouse cells compared to human cells gives rise to faster protein production, which ultimately allows mouse cells to proliferate and differentiate faster . In the PSDA-funded project, we seek to elucidate the basis of cytosolic NAD+/NADH differences between mouse and human cells by investigating the activity of biochemical shuttles that transport reducing equivalents from the cytosol to mitochondria. Specifically, we will test the hypothesis that mouse cells feature increased activity of the glycerol phosphate shuttle compared to human cells, thereby underlying differences in cytosolic NAD+/NADH and developmental rate. We will then leverage this new understanding to develop approaches for the modulation of developmental rate in vitro by manipulating glycerol phosphate shuttle activity. Acceleration of developmental rate would allow faster production of mature cell types from human induced pluripotent stem cells (iPSCs) for cell-based therapies and disease modeling; whereas its deceleration would provide new avenues to halt tumor growth and to slow down the aging process.
Juan D. Matute, MD
Department of Pediatrics, Division of Newborn Medicine
Director of Equity, Newborn Medicine
Instructor of Pediatrics, Harvard Medical School
Dr. Matute is a neonatologist and researcher in mucosal immunology at Massachusetts General Hospital (MGH). He obtained his Medical Degree from La Universidad de Antioquia (Colombia). Prior to his pediatric internship, he engaged in basic immunology research at Indiana University. Subsequently, he completed his pediatric residency through the Boston Combined Residency Program, receiving training at Boston Children’s Hospital and Boston Medical Center. He further specialized in Perinatal and Neonatal Medicine through the Harvard Combined Program. Following his clinical training, Dr. Matute joined MGH and Harvard Medical School HMS as an instructor. He dedicates his time to mucosal immunology research and clinical care in the MGH Neonatal Intensive Care Unit. Additionally, he leads initiatives focused on optimizing neonatal gastrointestinal health and serves as the Director of Equity in the Division of Newborn Medicine at MGH. Dr. Matute has conducted research on the host-microbiota interface starting in early life. He has focused his research efforts on how the intestinal microbiota and the host interact in the pathogenesis of intestinal inflammation and obesity. His work has received support from the American Heart Association, the Pediatric Scientist Development Program, the Crohn’s and Colitis Foundation, and the Harvard Digestive Disease Center.
Abstract: The role of Intelectin-1 in obesity
Genetic and environmental factors interact in the development of obesity from early life. However, research is still needed to understand how specific genes and environmental factors promote obesity development. The collection of microorganisms that live in our intestine is called the microbiota and is acquired after birth. Multiple lines of evidence have shown that the microbiota influences obesity development. In this project, we will define mechanistically how a genetic risk factor for obesity named Intelectin-1 regulates host metabolism potentially through the microbiota. Intelectin-1 is secreted to our gastrointestinal tract and interacts only with sugars found in the wall of microbes. We will study how Intelectin-1 in the gastrointestinal tract influences obesity using new genetically modified mice. This research project will enhance our understanding of Intelectin-1 on metabolic syndrome and will trailblaze the path to study the implications of Intelectin-1 interactions with the microbiota in humans with obesity. The proposed studies are relevant as they are expected to identify new insights into factors at the host and intestinal microbiome interface associated with metabolic syndrome, elucidate potential mechanisms, and, thus, novel therapeutic strategies for preventing obesity starting during the first years of life.
Veronica Clavijo Jordan, PhD
Department of Radiology
Instructor of Radiology, Harvard Medical School
Dr. Clavijo Jordan is an Instructor of Radiology at Harvard Medical School and at the Martinos Center for Biomedical Imaging at MGH. Dr. Clavijo Jordan received her doctoral degree in Biomedical Engineering from Arizona State University and completed her post-doctoral training at UT Southwestern Medical Center in Dallas. Dr. Clavijo Jordan’s research focuses on the design and evaluation of molecular probes that can act as sensors and report on organ function, disease status, and therapeutic response in cancer, inflammation, and fibrosis by MRI. She is specifically interested in imaging metals to infer the role they play in cellular and tissue processes and the development of disease. She is a recipient of an NCI K22 career development award for her studies in pancreatic ductal adenocarcinoma and the use of stimulated zinc flux in the exocrine pancreas as a noninvasive MRI biomarker of pancreatic cancer.
Abstract: Precision MRI of the Immunogenic Tumor Microenvironment as a Biomarker for Immunotherapy Response in Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is the most found malignant tumor in the pancreas with an overall 5-year survival rate of 11%. Treatment options for PDAC are limited, and surgical resection remains the only curative option albeit only attainable in 15-20% of cases due to diagnosis at an advanced stage. Therapies for patients with advanced disease are limited to chemotherapeutics and immunotherapy. However, despite the profound success with immunotherapy in other cancers, it is ineffective in PDAC largely due to the barriers introduced by the desmoplastic and immunosuppressive PDAC tumor microenvironment (TME). The TME is infiltrated by tumor-associated macrophages, and neutrophils (TANs) aiding in PDAC immune evasion. It was recently shown that suppression of TANs by Lorlatinib attenuate PDAC growth and improves immunotherapy response in mouse models. Recently, we developed a Fe-based MRI probe, FePyC3A, that becomes MRI visible in the presence of reactive-oxygen species (ROS) by oxidation of Fe2+ to Fe3+. We’ve established that FePyC3A-enhanced MRI can detect TANs in a mouse PDAC model and that their suppression by Lorlatinib treatment is measurable by FePyC3A-enhanced MRI. The primary hypothesis of this proposal is that noninvasive imaging of ROS activity in PDAC will predict response to treatment with anti-PD1 blockade.
Ronald G. Garcia, MD, PhD
Department of Psychiatry
Clinical Neuroscience Laboratory for Sex Differences in the Brain
Assistant Professor of Psychiatry, Harvard Medical School
Dr. Garcia is a researcher at the Clinical Neuroscience Laboratory for Sex Differences in the Brain at Massachusetts General Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. His main research interests include the study of pathophysiological mechanisms underlying the frequent co-occurrence of major depression and cardiovascular disease, and the development and translation of novel interventions for the regulation of these alterations. Dr. Garcia received his medical degree from Universidad Industrial de Santander, Colombia; earned a Ph.D. degree in neuroscience from Universidade de Brasilia, Brazil, and completed his postdoctoral training in neuroimaging and neuromodulation with professors Jill M. Goldstein and Vitaly Napadow at the Brigham and Women’s Hospital and Massachusetts General Hospital. His research has focused on the use of advanced neuroimaging and physiological tools for the evaluation of brain-heart interactions in depressed individuals and the development and optimization of non-invasive respiratory-gated vagus nerve stimulation as a potential neuromodulatory intervention for the regulation of sex-dependent alterations of brain circuitry responsible for mood, cardiac and vascular dysregulation in major depression. His long-term research goals include the clinical translation of this and other neuromodulation interventions for the treatment of psychiatric disorders and their comorbidity with cardio- and cerebrovascular disease.
Abstract: Effects of Transcutaneous Auricular Vagus Nerve Stimulation on the Regulation of Cerebrovascular Function in Midlife Adults with Recurrent Major Depression
Major depressive disorder (MDD) has been associated with a significantly increased risk for cerebrovascular disease and dementia. Although the mechanisms for this association are multifactorial, dysregulation of cerebrovascular function, characterized by blunted cerebrovascular reactivity and reduced cerebral blood flow, has been proposed as a main contributing factor for the development and progression of cerebrovascular disease and cognitive impairment in patients with MDD. Given the key role that these alterations may play in the development of debilitating conditions such as stroke and dementia, the evaluation of interventions that target mechanisms responsible for cerebrovascular dysregulation could have a significant impact in the reduction of disability associated with these disorders in patients with MDD. The primary goal of this study is to evaluate the effects of a novel, non-invasive neuromodulatory technique of the vagus nerve on the regulation of cerebrovascular function in MDD individuals. We will administer expiratory-gated transcutaneous auricular vagus nerve stimulation during a functional magnetic resonance imaging session and will evaluate sex-dependent effects of this intervention on the regulation of cerebrovascular reactivity, peripheral autonomic function, and inflammatory response of midlife adults with recurrent MDD. This initial pilot study will provide relevant information for the development of a sex-selective intervention with beneficial effects prior to later-life health outcomes associated with MDD.
Edmarie Guzmán-Vélez, PhD
Department of Psychiatry
Assistant Professor, Harvard Medical School
Dr. Guzmán-Vélez is a clinical neuropsychologist whose research focuses on identifying lifestyle factors and interventions that protect against the onset of cognitive impairment and dementia associated with neurodegenerative disorders, particularly Alzheimer’s disease (AD), and its mechanisms. In addition, her research aims to investigate these factors in different ethnic and racial groups to develop interventions that are culturally appropriate. She is the principal investigator of a study that aims to characterize markers of AD risk in adults with Post-Acute COVID-19 Syndrome (PASC), and of a clinical trial that aims to test whether nicotinamide riboside can help increase NAD+ and improve residual cognitive and neurological symptoms in young adults with PASC. In addition, she leads a project supported by an NIA K23 Mentored Patient-Oriented Research Career Development Award that seeks to elucidate whether aerobic fitness and physical activity can modify AD progression. Specifically, she examines the relation of fitness and physical activity levels with the accumulation of AD-related pathology measured by PET, resting-state functional systems, and cognitive decline in Presenilin-1 E280A carriers who will invariably develop early-onset dementia. She also investigates the role of plasma markers of immune function in cognitive decline and neurodegeneration in the preclinical stage and how it is related to physical activity. Dr. Guzmán-Vélez is staff neuropsychologist at the MGH Multicultural Assessment and Research Center, where she conducts culturally appropriate neuropsychological evaluations to mostly Latinos. She is also a strong advocate for increasing the representation of women and minorities in STEM and the co-director of the Sagrado Neuroscience Precollege Program.
Abstract: Evaluating the Effect of Long-COVID on Brain Injury and Cognitive Functioning
Initially thought to be an acute illness, resulting in death for some or full recovery in most, we are now appreciating that substantial numbers of COVID-19 illness survivors, including young and generally healthy people, experience persistent, significant, and often debilitating symptoms for months or years, known as Long-COVID or Post-Acute COVID-19 Syndrome (PASC). Symptoms range from neurological ("brain fog", headache) and neuropsychiatric (depression, poor sleep), to systemic symptoms (fatigue, pain). Symptoms, interfere with people's quality of life and daily functioning. It is hypothesized that these individuals may be at greater risk for neurodegenerative disease and dementia, including Alzheimer's disease. Yet, we do not understand why some people continue to experience cognitive difficulties and neurological symptoms, which are amongst the most common and debilitating PASC symptoms, and what this means for their future brain health. This three-year study aims to elucidate whether people with PASC, who have been experiencing "brain fog" and other symptoms for months after COVID-19 infection, may show evidence of inflammation and neural injury, as well as disrupted neural networks known to be important for memory and attention. Specifically, we will investigate, 1) the potential impact of PASC on blood markers of neuroinflammation and neural injury and degeneration; 2) the potential impact of PASC on the integrity of neural systems that underly cognitive functioning using resting-state functional connectivity; and 3) the relationship between markers of neuroinflammation and neural injury/degeneration and cognitive functioning in PASC. Findings will enlighten our understanding of the impact of PASC on the brain and its potential risk for future neurodegenerative disease, leading the way for better interventions and healthier aging.
Asishana A. Osho, MD, MPH
Department of Surgery, Division of Cardiac Surgery
Corrigan Minehan Heart Center
Assistant Professor of Surgery, Harvard Medical School
Dr. Osho is a surgeon in the Corrigan Minehan Heart Center at Massachusetts General Hospital who specializes in adult cardiac surgery, heart failure and thoracic transplantation. He earned a BA with high honors from Oberlin College, an MPH from the Yale University School of Public Health, and an MD from the Duke University School of Medicine. He completed residencies in general and cardiothoracic surgery at Massachusetts General Hospital/Harvard Medical School. Dr. Osho conducts clinical, translational and health services research to understand and improve health outcomes in patients undergoing cardiothoracic surgery. He also has significant experience designing and implementing clinical trials in cardiothoracic surgery. Dr. Osho's research projects have been supported by the American Heart Association, the Thoracic Surgery Foundation, Intuitive Surgical and the Society of Black Academic Surgeons.
Abstract: A Prospective Trial to reduce the impact of Atrial Fibrillation in Cardiac Surgery using a Standardized Pharmacosurgical approach and Wearable Biosensors
Atrial fibrillation is a type of irregular heart rhythm caused by uncoordinated electrical signaling in the heart. This condition occurs commonly after cardiac surgery and is associated with elevated risk of further complications including stroke, heart failure and death. Atrial fibrillation occurring after cardiac surgery – Postoperative Atrial Fibrillation – is poorly understood with gaps in the knowledge about optimal prevention, duration of disease and patterns of presentation. We propose to advance knowledge in the field by performing a prospective randomized study to compare the rate of postoperative atrial fibrillation in cardiac surgery patients who receive standard of care versus those who receive a combination of two preventative interventions. The interventions include a) administering amiodarone (a drug that regulates electrical signaling in the heart), and b) performing a procedure called a posterior pericardiotomy (which improves blood drainage and can reduce the risk of atrial fibrillation). Integration of data from wearable biosensors placed on study participants at the time of discharge will delineate the duration and characteristics of atrial fibrillation in discharged patients. Overall, this project innovates clinically and technologically to advance our understanding of a major cause of morbidity and mortality in cardiac surgery.
Jacqueline A. Seiglie, MD, MSc
Endocrinologist, MGH Division of Endocrinology
Assistant Professor of Medicine, Harvard Medical School
Dr. Seiglie is an Assistant Professor of Medicine at Harvard Medical School and a practicing endocrinologist and diabetologist at MGH. Her research focuses on the epidemiology of type 2 diabetes in Latin America and on the development of scalable interventions to improve diabetes self-care among Latino adults. Born and raised in Santiago, Chile, she has had a long-standing interest in working to improve diabetes care for Latino adults through clinical care and research. Dr. Seiglie received her medical degree from Harvard Medical School and her Master’s in Community Health and Welfare from the Universitat Autonoma de Barcelona. She completed both her Internal Medicine residency and fellowship training in Endocrinology, Diabetes and Metabolism at MGH. In addition to the CDI Physician-Scientist Development Award, her work is supported by a K23 Grant from the NIH/NIDDK. She was the inaugural recipient of the 2022 Martin Research Prize in Population Health Sciences research and is a past recipient of the Harvard Catalyst KL2 Award, NIH/NIDDK Loan Repayment Award, and The John T. Potts Jr. Pilot Award Program.
Abstract: REACH-Es: A Culturally Tailored Adaptation of an mHealth Tool to Improve Diabetes Self-care Among Hispanic Adults
Non-adherence to diabetes medications is a leading contributor to suboptimal diabetes management among Hispanic adults, who are nearly twice as likely to have diabetes-related complications as non-Hispanic White individuals. Digital health technology can improve medication adherence and is recommended by the American Diabetes Association to support diabetes self-care. Text message-based mobile health (mHealth) platforms, in particular, have the potential to engage Hispanic adults, who are more likely to own a cellphone than non-Hispanic White individuals and who are less likely to use other digital health tools, such as patient portals and app-based platforms. Interactive text message-based mHealth platforms with personalized content are features associated with higher user engagement. An mHealth tool with these key features is REACH (Rapid Encouragement/Education And Communications for Health), a low-cost, interactive text messaging platform shown to improve diabetes medication adherence and hemoglobin A1c in an English-speaking, low-income population, while achieving a retention rate of over 90% at 12 months. REACH has not yet been adapted to a Spanish-speaking context and could be a suitable mHealth tool to improve diabetes medication adherence among Hispanic adults with type 2 diabetes. In this proposal, we will adapt REACH to a Hispanic population (REACH-Español) using community-engaged research and mixed-methods in preparation for a randomized pilot study that will assess the feasibility, acceptability, and preliminary efficacy of REACH-Es among Hispanic adults with type 2 diabetes and suboptimal diabetes management.
Mabel Toribio, MD
Department of Medicine, Division of Endocrinology
Assistant Professor of Medicine, Harvard Medical School
Dr. Toribio is an Endocrinologist at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School. Dr. Toribio’s research focuses on cardiometabolic disease risk in diverse patient populations. She has published on novel techniques to quantify arterial macrophage infiltration as well as on effects of statins on markers of immune activation and on the proteome among people with HIV. She has also published on the effects of newly initiated antiretroviral therapy on arterial inflammation and cholesterol efflux in this population. Her latest research investigates cardiometabolic effects of gender-affirming hormonal therapy among gender-diverse populations. Dr. Toribio is a past recipient of an individual NIH NRSA, a Harvard Catalyst KL2 Award, the Harvard University CFAR Developmental Core Grant, the MGH DOM Sanchez and Ferguson Research Faculty Award, and an MGH DOM COVID-19 Junior Investigator Support Initiative Grant. Dr. Toribio is also a current recipient of an NIH K23 Mentored Patient Oriented Career Development Award and an American Heart Association-Harold Amos Medical Faculty Development Award from the Robert Wood Johnson Foundation. In addition to her research endeavors, Dr. Toribio also is deeply invested in teaching, mentoring and recruiting trainees from under-represented backgrounds in medicine/science.
Abstract: ImmuNomodulatory EffectS of PCSK9 Inhibition: A TaRgeted Molecular Imaging AppRoach (INSPIRAR)
Cardiovascular disease (CVD) represents the leading cause of death worldwide. While medications, such as statins, significantly reduce atherosclerotic CVD (ASCVD) risk by lowering low density lipoprotein levels, they may also have pleiotropic effects on inflammation. The immunomodulatory effects of these medications are relevant to ASCVD risk reduction given that inflammation plays a central role in atherosclerotic plaque formation (atherogenesis) and influences the development of vulnerable plaque morphology. Patients on statins, however, may have residual inflammation contributing to incident ASCVD despite the potent LDL-lowering effects of statins. While new therapies, such as proprotein convertase subtilisin/kexin type 9 (PSCK9) inhibitors, further reduce incident ASCVD and drastically reduce LDL-C below that achieved by statin therapy alone, PCSK9 inhibitors may also have pleiotropic effects on inflammation. Thus, PCSK9 inhibitors may help reduce arterial inflammation to a level closer to that of patients without ASCVD. This study will apply a novel targeted molecular imaging approach, technetium 99m (99mTc)-tilmanocept SPECT/CT, to determine if residual macrophage-specific arterial inflammation is present with statin therapy and the immunomodulatory effects of PSCK9 inhibition. Given the continued high mortality and morbidity attributable to ASCVD, strong imperatives exist to better understand the immunomodulatory effects of lipid lowering therapies and residual inflammatory risk. This understanding, in turn, will inform the development of new ASCVD preventative and treatment strategies as well as elucidate other indications for established therapies.
Eman Akam, PhD
Department of Medicine, Cardiology Division
Instructor, Harvard Medical School
Dr. Akam is an investigator at the Massachusetts General Hospital Cardiology Division and an Instructor in Medicine in the Sosnovik group at the Cardiovascular Research Center. Dr. Akam received her PhD in Chemistry from the University of Arizona and completed her postdoctoral training with professor Peter Caravan at the Martinos Center for Biomedical Imaging at MGH. Dr. Akam’s research focuses on development of imaging tools that can inform on molecular mechanisms of fibrotic heart and lung diseases. Additionally, Dr. Akam is passionate about mentoring, outreach, and the advancement and equal representation of historically marginalized communities in STEM fields. Dr. Akam is the recipient of the New England Educational Opportunity Association (NEOA) 2019 Rising Star award, and the co-founder of the Melanated and Dedicated (MaD) Scientist outreach program.
Abstract: Targeted Molecular Imaging of Cardiac Fibrogenesis in Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart failure (HF) with preserved ejection fraction (HFpEF) is a poorly understood syndrome that is projected to become the leading cause of HF in the next decade. Twenty years of research and numerous clinical trials with over 15,000 patients have failed to produce any effective therapies. A major hurdle in HFpEF drug development is the lack of methods that can sensitively detect and diagnose HFpEF, and the clinical diagnosis of HFpEF remains challenging. One of the central features of HFpEF is the development of scar tissue (fibrosis) in the heart. We have previously demonstrated that fibrogenesis-targeted MRI contrast agents can sensitively detect early stages of lung fibrosis and distinguish between active and stable remodeling. The aim of this proposal is to use a targeted imaging agent to detect active fibrosis in the heart in a mouse model of HFpEF. This approach has the potential to address many of the challenges we face in HFpEF research and clinical care. Molecular imaging of a biochemical feature of HFpEF would enable quantification of disease burden at the molecular level, which in turn enables diagnosis, grading/staging of the disease as well as monitoring its progression. The outcomes of this work have the potential to accelerate our understanding of HFpEF and provide more effective approaches to development of HFpEF therapies.
Efren Flores, MD
Department of Radiology
Assistant Professor of Radiology, Harvard Medical School
Officer, Radiology and Community Health Improvement & Equity
Dr. Flores completed his Diagnostic Radiology residency and fellowship at Massachusetts General Hospital (MGH), where he currently serves as faculty in Thoracic Imaging and as Associate Professor at Harvard Medical School. Dr. Flores has served in several leadership roles at MGH, including his current role as Vice Chair for Radiology Diversity Equity, and Inclusion (DEI), and as the founding Director of the Radiology Inclusion and Systemic Equity (RISE) Center. Dr. Flores is a nationally recognized health services researcher focused on understanding health disparities and advancing health equity among historically underserved racial and ethnic minority communities. In recognition of his health disparities research advancing health equity, Dr. Flores has been awarded numerous awarded grants, invited to multiple presentations nationally, and peer-reviewed publications. Dr. Flores health equity work is guided by the overarching goal of fostering trust and a sense of belonging. In recognition for his work, Dr. Flores was selected as one of the inaugural National Academy of Medicine Scholars in Diagnostic Excellence in 2021, and currently serves in several institutional and national committees, including as Co-Chair of the Health Equity Committee for the Radiological Society of North America and as Associate Editor of Health Equity for the Journal of the American College of Radiology.
Abstract: Health Equity & Access for Lung Screening (HEALS): A study of multimodal digital outreach for lung cancer screening among Latino current and former smokers
Lung cancer remains the leading cause of cancer-related death among Latinos, and existing disparities in lung cancer outcomes have been exacerbated by the COVID-19 pandemic. Lung cancer screening (LCS) can serve as a pillar to bridge disparities in lung cancer outcomes through early detection among Latino communities. However, despite the proven benefits of LCS in reducing lung cancer mortality, only 10-20% of the eligible population has been screened; the proportion of eligible Latinos participating in LCS is likely to be lower. This proposal seeks to reduce LCS disparities among Spanish speaking Latinos and Latinos with limited English proficiency served by our health care system by implementing a multimodal digital outreach intervention to increase LCS engagement among eligible Latino individuals using a 3-tiered approach: 1) Accurate identification of smoking history to increase LCS opportunities; 2) Digital outreach tailored for Latino communities to increase LCS awareness; 3) Measuring efficacy to increase LCS participation among Latino patients. The specific aims of this proposal are to 1) assess the community needs and emerging barriers to LCS through conducting a survey with Latino communities served by our healthcare system and (2) to employ a mixed-methods approach to explore preferences for message source, channel, and content about LCS during the ongoing COVID-19 to inform a future, culturally tailored LCS outreach intervention among Latino communities. The overarching goal of this proposal is to increase LCS participation and decrease lung cancer disparities by developing a framework to identify barriers to LCS, engage the Latino community in the development of a multimodal digital outreach intervention, and determine the best approach to increase LCS participation among eligible Latino individuals.
Yasmin G. Hernandez-Barco, MD
Pancreatic Diseases, Division of Gastroenterology
Instructor, Harvard Medical School
Dr. Hernandez-Barco is a Gastroenterologist and Medical Pancreatologist for the Division of Gastroenterology with a clinical focus on caring for patients with acute pancreatitis, chronic pancreatitis, pancreatitis of unknown etiology, exocrine pancreatic insufficiency, pancreatic cysts, and pancreatic cancer. Dr. Hernandez-Barco is a physician-scientist and studies the immunobiology of pancreatic cancer precursor lesions and the role of the immune system in malignant progression of pancreatic cancer. She is a post-doctoral fellow in the laboratory of Nabeel Bardeesy, PhD, an expert in pancreatic and biliary cancers. She is actively involved in research which includes developing technologies for the early detection of pancreatic cancer and pancreatic cysts and developing clinical diagnostic tools and treatments in the management of various subtypes of pancreatitis.
Dr. Hernandez-Barco received her medical degree from SUNY Stony Brook School of Medicine where she was inducted into the Alpha Omega Alpha and Gold Humanism Honors Societies and awarded the Glasgow-Rubin Citation for academic achievement. She completed her residency and chief residency at the Icahn School of Medicine at Mount Sinai. Dr. Hernandez-Barco completed her Gastroenterology and Hepatology Fellowship in the Division of Gastroenterology at MGH. She completed an additional year of advanced fellowship training in Medical Pancreatology at MGH and Brigham and Women’s Hospital. She is the past recipient of numerous grants including Andrew L Warshaw Pancreatic Cancer Research Award and Dana Farber Harvard Cancer Center Career Development award. She is actively involved in gastroenterology and pancreatic professional societies and serves on several national committees including the American College of Gastroenterology’s (ACG) Food and Drug Administration Related Matters Committee, ACG Technology and Innovation Committee, and ACG Young Physician Scholar Program Steering Committee.
Abstract: Molecular Mechanisms of Intraductal Papillary Mucinous Neoplasms
Intraductal papillary mucinous neoplasia (IPMN) is a cystic tumor of the pancreas seen in 10% of the population. Retrospective data shows that >1/3 of patients with IPMN are at risk of developing invasive pancreatic ductal adenocarcinoma (PDA), one of the deadliest malignancies. Unfortunately, current clinical and imaging criteria are inadequate for predicting the likelihood of IPMN becoming malignant. The only treatment for IPMN or resulting PDA is surgical resection, which carries significant morbidity (40-50%) and mortality (2%).
Thus, critical challenges include the need to identify patients who are at risk for developing PDA and to improve diagnostic methods and develop preventive therapies, as well as to develop more targeted treatments for IPMN-derived PDA.
We have developed a series of novel genetically engineered mouse models (GEMMs) and have access to one of the largest surgically resected IPMN biorepositories in the world. From these models, we discovered that IPMNs have a distinct immune microenvironment that is rich in tumor suppressive cells and is controlled by specific genetic mutations found only in IPMNs. In this proposal, we aim to further classify these tumor subtypes and identify factors related to cancer progression so that we may uncover strategies for early intervention or treatment of advanced disease.
Gabriela Soriano Hobbs, MD
Department of Medicine, Cancer Center
Assistant Professor, Harvard Medical School
Dr. Hobbs received her bachelor’s degree from Tufts University and her medical degree from Mount Sinai School of Medicine. She did her internal medicine training at Brigham and Women’s Hospital and completed hematology/oncology fellowship training at Memorial Sloan Kettering Cancer Center. Dr. Hobbs is the clinical director of the leukemia service at Mass General. Her clinical and research focus is on the care of patients with a group of chronic leukemias called myeloproliferative neoplasms (MPN). Her research focuses on developing clinical trials for patients with MPNs. In addition to drug trials, she is investigating how patients with MPNs respond to vaccination in general, and the COVID vaccine in particular. In addition to the PSDA award, her work is supported by an American Society of Hematology Harold Amos Faculty Development Award. She is a past recipient of the K-12 Paul Calibresi award, the American Cancer Society Institutional Research Grant, an Eleanor Miles Shore award, an American Society of Clinical Oncology Young Investigator Award, and the CDI Sanchez Ferguson Award.
Abstract: In-depth investigation of immune response to COVID-19 vaccination in patients with myeloproliferative neoplasms
The COVID-19 pandemic highlighted how vulnerable we are to disease without vaccination. A year into the pandemic, there are several approved vaccines. However, little is known about how cancer patients respond to vaccination. I am a leukemia specialist and treat patients with leukemias called myeloproliferative neoplasms (MPN). MPN patients are immunosuppressed, and studies show that only 45% develop immunity to the yearly influenza vaccine. For this proposal, I collected blood from MPN patients and healthy volunteers before and after receiving COVID-19 vaccines to learn how they respond to vaccination. First, we measured antibody titers before and after vaccination. Specifically, we assessed cumulative IgG, IgA and IgM anti-spike by ELISA (binding site) and we performed quantitation of spike-specific IgG. Second, T-cell responses to COVID-19 vaccinations were measured utilizing interferon gamma ELISpot assays. These studies demonstrated that patients with more indolent MPNs essentially have normal immune response to vaccination, patients with myelofibrosis had a significantly impaired to vaccination. Our results were published in Leukemia in 2022. Lastly, we will use mass cytometry to get an in depth look at how different cells in the immune system interact in response to vaccination. Our goal is to gain a deeper understanding of the immune status of patients with leukemia and to learn how they respond to vaccination. Ultimately, we will continue to investigate how leukemia patients, and immunocompromised patients, respond to vaccination to better guide the care of our patients.
Karla Ramos Torres, PhD
Department of Radiology, Gordon Center for Medical Imaging
Postdoctoral Research Fellow, Harvard Medical School
Dr. Ramos Torres is a postdoctoral research fellow at the Gordon Center for Medical Imaging at Massachusetts General Hospital and Harvard Medical School. She has broad training at the interface of chemical biology, organic, inorganic and radiochemistry applied to imaging. Her research interests are directed at the application of chemical and chemical biology strategies to support the discovery and development of technologies for disease diagnosis, monitoring and treatment. Dr. Ramos Torres received her bachelor’s degree in Chemistry from the University of Puerto Rico, Río Piedras and earned her PhD in Chemistry and Chemical Biology at the University of California, Berkeley. Her research as a research fellow at the Gordon Center focuses on the development and application of new small molecule PET radiopharmaceuticals designed to better understand neurological disorders.
Abstract: Imaging brain injuries in animal models using PET
Disruptions to the myelin sheath, the protective layer that covers nerve cells in the brain and spinal cord, can affect neuronal ability to propagate action potentials needed for the proper function of motor, sensory and cognitive skills. Demyelination is a hallmark in a wide range of neurological pathologies, including multiple sclerosis, leukodystrophies, Alzheimer’s disease, traumatic brain (TBI) and spinal cord injury (SCI) and stroke, among others. However, demyelination is not a stand-alone feature in these disorders, being usually accompanied by other processes including neuroinflammation. It is therefore attractive to identify and develop methods that can accurately quantify and assess myelin status in order to diagnose and monitor disease progression and treatment.
Currently, myelin content in demyelinating diseases is evaluated with MRI. However, while MRI is highly sensitive to demyelination, it cannot discriminate between demyelination and other simultaneous processes present in these pathologies, such as inflammation and axonal loss. Due to its biochemical specificity and quantification ability, positron emission tomography (PET) can serve as a complementary technique to MRI. [18F]3F4AP, a recently developed 4-aminopyridine (4AP) based PET tracer that binds to voltage-gated K+ channels, has been proven to visualize demyelination in rodent models of multiple sclerosis (MS). The proposed research project seeks to assess the potential utility of this radiotracer to identify white matter injury in a variety of pathologies, namely models of brain injury, and distinguish between the progression of demyelination and inflammation.
The specific goals of this proposal are to study [18F]3F4AP, in combination with the known neuroinflammation tracer [11C]PBR28, as a tool to evaluate demyelination and inflammation with PET imaging in mouse brain injury models for open-head injury and stroke. Mice will be subjected to a well-characterized mouse model of TBI, open-head controlled cortical impact (CCI), and monitored in a longitudinal PET imaging study with both radiotracers to evaluate focal changes in myelin content and/or inflammation, followed by corroboration with histopathological and histochemical characterization of the brain tissue. Additionally, the study will expand to mouse models of stroke to study the pathologies of demyelination and neuroinflammation with imaging, histology and behavioral methodologies.
Julia M. Rosenbloom, MD
Department of Anesthesia, Critical Care and Pain Medicine,
Division of Pediatric Anesthesia
Assistant Professor in Anesthesia, Harvard Medical School
Dr. Julia Rosenbloom is a pediatric anesthesiologist at Massachusetts General Hospital for Children. She earned a BA summa cum laude from Harvard College, an MA from Queen’s University Belfast (as a George Mitchell Scholar), and an MD from the University of Pennsylvania School of Medicine; she will finish an MPH at the T.H. Chan Harvard School of Public Health in May 2021. Dr. Rosenbloom completed an anesthesiology residency at Yale-New Haven Hospital and a pediatric anesthesia fellowship at Children’s Hospital Philadelphia. Her research focuses on racial and ethnic disparities in perioperative care in the United States, with a particular focus on pediatric populations. She was supported by a T32 Research Training for Harvard Anesthetists and was a past recipient of the Eleanor and Miles Shore 50th Anniversary Fellowship.
Abstract: Racial Differences in Treatment of Pediatric Preoperative Anxiety: A Multilevel and Mixed Methods Approach
A majority of the approximately six million children who undergo anesthesia annually in the United States will experience preoperative anxiety, putting them at risk for poor postoperative outcomes. Several studies have suggested that Black non-Latino and Latino children may receive different treatment for preoperative anxiety than White non-Latino patients: specifically, Black and Latino patients may be less likely to receive midazolam (a benzodiazepine) and more likely to have parental presence at induction (PPAI). However, these findings derive from single-institution studies which neither used established disparities methodology nor considered mediating factors or associated clinical outcomes.
To address this knowledge gap, we will perform a mixed-methods study within the Mass General Brigham Health System to explore the magnitude, mechanisms, associated clinical consequences, and provider perspectives of racial/ethnic disparities in treatment of pediatric preoperative anxiety. We will first characterize the extent by which management of preoperative anxiety varies by patient race/ethnicity and is explained by provider and hospital level factors. We will also determine whether specific treatments (PPAI or midazolam) are associated with any of four pre-identified poor clinical outcomes and evaluate the potential for heterogeneity of treatment effect by patient race/ethnicity. Finally, we will conduct semi-structured interviews to identify as-yet unexplored clinicians’ perspectives on treatment of pediatric preoperative anxiety. Our findings are expected to inform interventions such as protocolized clinical pathways and educational interventions for informing clinicians.
David A. Alagpulinsa, PhD
Department of Medicine, Mass General Hospital
Instructor in Medicine, Harvard Medical School
Dr. Alagpulinsa is an Instructor in Medicine at Mass General Hospital and Harvard Medical School. He earned a PhD in Interdisciplinary Biomedical Sciences from the University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. Dr. Alagpulinsa is a past recipient of the Mass General 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. His research interests include bone marrow function, hematopoiesis, and genome maintenance, especially type 1 diabetes and hematologic malignancy.
Abstract: Harnessing bone marrow function in type 1 diabetes
Type 1 diabetes (T1D) is characterized by autoimmune-mediated destruction of insulin-producing beta cells of pancreatic islets. Currently without a cure, diagnosis with T1D necessitates lifelong exogenous insulin replacement therapy. Although this is life-sustaining, physiological glucose control is hardly attainable, with most patients ultimately succumbing to cardiovascular complications. The incidence of this incurable disease is on a global rise, affecting 64, 000 Americans annually and accounts for an annual loss in income and healthcare expenditure of $14.4 billion to the US alone. The bone marrow is the predominant residence of hematopoietic stem cells (HSCs) that regenerate all immune cells throughout life. Additionally, the BM is endowed with other stem and progenitor cells and regulatory T cells (Tregs) that have superior immunoregulatory ability and can abrogate the autoimmune response that destroys beta cells, while supporting tissue regeneration. Unfortunately, the BM is also “sick” in T1D, causing dysregulation of immune cell production, as well as impaired function and peripheral mobilization of immunoregulatory stem/progenitor and regulatory T cells. This promotes disease development and associated cardiovascular complications. The overall goal of this PSDA research project is to use single cell sequencing analysis to understand how autoimmune diabetes impacts the BM microenvironment and to design novel therapeutic strategies to rescue BM function and induce mobilization of stem/progenitor cells and Tregs mobilization into the blood circulation and pancreatic islets to treat autoimmune diabetes. These studies may uncover new pathogenic mechanisms in T1D and treatment strategies.
Ibiayi Dagogo-Jack, MD
Department of Medicine, Cancer Center
Assistant Professor of 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 Mass 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 targeted therapies and developing novel selective therapies for lung cancer and mesothelioma. In addition to the CDI PDSA, her work is currently supported by a K12 award, SPORE 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 are defined by an initial dependence on ALK signaling that renders these tumors markedly sensitive to ALK targeted therapies. However, the majority of ALK+ lung cancer 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. In this grant, we are exploring whether less invasive strategies, i.e. plasma analysis, can identify genetic alterations that are critical to survival of resistant ALK-positive lung cancers. Furthermore, we will conduct a clinical trial to assess the activity of several combination therapies in patients with ALK-positive lung cancer with ALK-independent resistance. As there are no approved selective regimens 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 treatment strategies.
Christian 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. Ufere, MD
Department of Medicine, Gastroenterology Division, Liver Unit
Clinical and Research Fellow, Harvard Medical School
Nneka N. Ufere, MD is a Transplant Hepatologist 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 completed her medical degree at Washington University in St. Louis School of Medicine in 2012 where she was a recipient of the Glasgow-Rubin Citation for Academic Achievement 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 completed her Gastroenterology fellowship in 2020 and Transplant Hepatology fellowship in 2021 at Massachusetts General Hospital. She is currently pursuing a Master of Science in Clinical Epidemiology degree at the at the Harvard T. H. Chan School of Public Health.
She is a member of the Massachusetts General Hospital Cancer Outcomes Research and Education Program and the Mongan Institute, 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 care for patients with advanced liver disease and their caregivers. Her work is currently supported by the American Association for the Study of Liver Diseases Clinical, Translational and Outcomes Research Award, the Massachusetts General Hospital Physician Scientist Development Award, and a GI Innovation and Collaboration Award from the MGH GI Division. She is a past recipient of the NIH Loan Repayment Award, the American College of Gastroenterology Clinical Research Pilot Award and the American Association for the Study of Liver Diseases Advanced/Transplant Hepatology Award.
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.
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 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
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.
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:
- Determine the feasibility and validity of an online medication database compared to EMR data abstraction to measure HT adherence and persistence
- Evaluate the impact of TRIP on HT early discontinuation and adherence among 342 intervention patients and 263 historic controls with HR+ breast cancer
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.
J. 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.hide
Camille 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
Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology, 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. She is also the PI of the Boston clinical site of a multicenter longitudinal observational study of glycemia in pregnancy assessed with continuous glucose monitoring. 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, 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, MBA, FAAP, FACP, FAHA, FAMWA, FTOS
Associate Professor, Medicine & Pediatrics, Harvard Medical School
Obesity Medicine Physician Scientist
Director of Equity, MGH Medicine, Endocrine Division
Director of Diversity, Nutrition Obesity Research Center at Harvard (NORCH)
Core Faculty, MGH Mongan Institute of Health Policy
Leadership Team, MGH Midlife Women’s Health Center
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 completing her MPH, she received the Gold Congressional Award, the highest honor 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) established 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. She was chosen for The Obesity Society Clinician of the Year in 2020. In 2021, she was awarded the MMS Grant Rodkey Award for her dedication to medical students and the AMA Dr. Edmond and Rima Cabbabe Dedication to the Profession Award, which recognizes a physician who demonstrates active and productive improvement to the profession of medicine through community service, advocacy, leadership, teaching, or philanthropy. She is the 2021 Recipient of the Emory Rollins School of Public Health Distinguished Alumni Award. In 2022, the National Academy of Medicine selected her as a Scholar in Diagnostic Excellence.
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 Division
Instructor in Medicine, Harvard Medical School
David Perez, MD, MMSc
Departments of Neurology and Psychiatry
Director, Functional Neurological Disorder Unit & Research Group
Associate 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 Mass General, Dr. Perez has developed a new multidisciplinary clinical program for the diagnostic evaluation and management of patients with Functional Neurological Disorder. In parallel, he has established a neuroimaging research program investigating biomarkers of symptom severity, disease-risk and prognosis in Functional Neurological Disorder. In these settings, Dr. Perez is the Director of the MGH Functional Neurological Disorder Unit within the Cognitive Behavioral Neurology Unit, and the Director of the Functional Neurological Disorder Research Group. For his efforts, Dr. Perez has been recognized as a Fellow of the American Academy of Neurology and the American Neuropsychiatric Association.
Abstract: Neuroimaging Biomarkers of Symptom Severity, Disease Subtype and Prognosis in Functional Neurological Disorder
Motor Functional Neurological Disorder (a.k.a. Conversion Disorders) is a highly prevalent and disabling neuropsychiatric disorder, comprising about 16% of outpatient neurology referrals; this includes patients with Functional Seizures, Functional Movement Disorders and Functional Limb Weakness. Motor Functional Neurological Disorder and other brain-mind-body conditions 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 Disorder. 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 Disorder. This research leverages a large and relatively unique patient cohort in the newly established Functional Neurological Disorder Unit at the Massachusetts General Hospital in the Department of Neurology.
Yakeel Quiroz, PhD
Departments of Psychiatry and Neurology
Director, Familial Dementia Neuroimaging Lab
Director, Multicultural Assessment and Research Center-MARC
Associate 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.
Her research interests include brain imaging, genomics, early detection and preclinical biomarkers of Alzheimer’s disease and other dementias. She is the principal investigator of the Colombia-Boston (COLBOS) longitudinal biomarker study of autosomal-dominant Alzheimer’s disease, which follows individuals from the world’s largest extended family with a single, AD-causing mutation (E280A in Presenilin1). Dr. Quiroz’s research has focused on characterizing biological and physiological 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’s work has been recognized with several awards, including an NIH Director’s Early Independence Award, the FABBS Foundation Early Career Impact Award, the MGH Research Scholar Award and the Alzheimer’s Association Inge Grundke-Iqbal Award for Alzheimer’s Research.
Dr. Quiroz is also the Director of the MGH Multicultural Assessment and Research Center (MARC), and has strong clinical interests in the assessment of Latino patients impacted by brain disorders.
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, PhD
Department of Pathology
Assistant Professor of Pathology, Harvard Medical School
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
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.
Cesar M. Castro, MD, MMSc
Director, Gynecologic Oncology Program, MGH Cancer Center
Director, Cancer Program, MGH Center for Systems Biology
Faculty Co-Director for Research, MGH Center for Diversity and Inclusion
Chair, MGB Phase I Cancer Clinical Trials
Associate Professor of Medicine, Harvard Medical School
Dr. Castro, MD, MMSc is an Associate Professor of Medicine at Harvard Medical School and Director of the Gynecologic Oncology Program 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 also directs the Cancer Program within the MGH Center for Systems Biology. He serves on the steering committee for the National Cancer Institute Liquid Biopsy Consortium. Dr. Castro graduated from the University of California, Berkeley and received his medical degree from the UCSF School of Medicine where he also completed his Internal Medicine residency training. Dr. Castro completed an adult oncology fellowship from the Dana-Farber / Mass General Brigham Cancer Care program. During this period, he also received a MMSc from Harvard Medical School. Dr. Castro has received funding from the National Institutes of Health, Department of Defense, Robert Wood Johnson Foundation, and Ovarian Cancer Research Fund, among various other sources. He has also been the recipient of the CDI/ECOR Physician Scientist Development Award.
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.
Oluwaseun 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.
Department of Medicine, Division of Infectious Diseases
Associate Professor of Medicine, Harvard Medical School
Associate Professor, Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health
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 broadening our understanding of host-pathogen and immune responses during human infection and vaccination with Vibrio cholerae (the cause of cholera) and Salmonella enterica serovar Typhi (the primary causes of enteric fever). Work in her laboratory is primarily focused on: 1) application of high-throughput proteomic and genomic platform technologies to identify immunogenic antigens for vaccine and diagnostic development for these infections, 2) development of rapid diagnostics and seroepidemiological tools for S. Typhi and Paratyphi A infection, and 3) characterization of immune responses during human infection and vaccination with enteric infections. With the advent of the SARS-CoV-2 pandemic, she broadened her research efforts to obtaining a better understanding of the antibody-mediated immunity to COVID-19.
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, 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.
Miguel 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, 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 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 200+ 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. In 2007 he received an MGH Physician-Scientist Development Award (PSDA) and 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
William 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.
Sherri-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. Dr. Burnett-Bowie 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.
Support Our Work
When you support the Massachusetts General Hospital Center for Diversity and Inclusion, you are making a significant contribution to create an environment where students, residents and physicians who are underrepresented in medicine want to learn, train and advance.