Brigham And Women'S Hospital

NIH Research Projects · FY 2025 · 1990-08

The goal of this training grant program is to prepare outstanding M.D, M.D-Ph.D. and Ph.D. trainees for careers as scientific leaders in HIV research. Despite enormous progress over more than 40 years towards reducing the morbidity and mortality from HIV/AIDS, substantial challenges remain. These include developing a safe and effective vaccine; developing an HIV cure; improving the treatment and management of opportunistic infections such as tuberculosis that burden patients with HIV in resource-limited settings; managing the threat of antiretroviral drug resistance; reducing HIV-associated immune activation that leads to end-organ disease and accelerates aging; and improving long-acting antiretroviral drugs for treatment and prevention of HIV. Progress on these fronts requires basic and translational research to further our understanding of the molecular biology, pathogenesis, immunology, prevention and therapeutics of HIV/AIDS. Over the past 35 years this program has trained 104 post-doctoral fellows, the majority of whom have gone on to leadership positions in academia, industry and government. This program will provide in-depth laboratory experience in a specific research area of HIV-related virology, immunology, epidemiology, molecular genetics, molecular therapeutics, genomics and/or systems biology. Criteria for selecting trainees will include prior training record, aptitude for research and demonstrated commitment to a research career. Applicants will be selected by a Training Advisory Committee (TAC); 5 post-doctoral trainees will be selected annually and appointed for a minimum of 2 years. Basic elements of the program include: 1) in-depth research training through laboratory investigation of a specific scientific question in a particular area of HIV research under mentorship of a senior investigator; 2) a didactic program consisting of appropriately chosen courses specific to the trainee’s career goals; 3) frequent exposure to seminars, workshops and colloquia related to HIV; regular review of progress by individual Research Advisory Committees and the TAC. In addition, instruction in the preparation of competitive proposals for funding, with a particular emphasis on applications for K and other career development awards, including foundation awards, will be provided. Independently funded junior and senior faculty at these institutions constitute the training faculty, representing various HIV-related disciplines. The faculty collaborate extensively with one another on HIV research and will collaborate in directing this training program. Faculty will receive formal mentor training and periodic refreshers to support effective mentorship, foster independence and promote professional development. The Harvard University Center for AIDS Research and the Harvard Medical School Clinical and Translational Science Center (Harvard Catalyst) provide additional institutional resources that enrich the scientific experience and career development of our trainees and faculty.

NIH Research Projects · FY 2025 · 1987-07

ABSTRACT Channing Division of Network Medicine Training Program in Systems Approaches to the Epidemiology, Genetics, and Genomics of Lung Diseases This training program is a competing continuation of a program funded by Institutional Ruth L. Kirschstein National Research Service Award T32 HL007427. The program, which has operated continuously for the past 46 years, focuses on chronic respiratory diseases that are major public health problems--asthma and chronic obstructive pulmonary disease (COPD). Based on our current limited understanding of these complex lung diseases, there is a critical need for individuals trained in the application of systems approaches to epidemiology, genetics, and genomics to perform quantitative research in respiratory biology. This T32 program is instrumental in meeting this need, successfully training independent research investigators who go on to lead their own research programs across the U.S. and Canada. The program provides research training in seven areas: systems genetics; systems biology and network modeling; transcriptomics; functional genetics; other Omics; epigenomics; and bioinformatics/data science. Six postdoctoral and two predoctoral training positions are requested in this proposal, with a typical appointment duration of three years. The trainees interact with a pool of 36 faculty members in the seven interrelated research areas. Each trainee will have the opportunity to become involved in the design, execution, and analysis of ongoing federally funded research projects as well as develop an independent career path. Trainees’ research is conducted at the Channing Division of Network Medicine, a research division of the Department of Medicine at Brigham and Women's Hospital (BWH) and Harvard Medical School (HMS). Predoctoral trainees work toward a Ph.D. in network science, biostatistics, or epidemiology. Postdoctoral trainees undertake didactic classroom work leading to a Master of Science (M.S.) in epidemiology or a Master of Public Health (M.P.H.) degree at the Harvard T.H. Chan School of Public Health (HSPH) or a Master of Medical Science (M.M.Sc.) degree in bioinformatics at HMS. After completing our program, trainees will be eligible to assume faculty positions in systems biology/biostatistics or genetics/genomics. Trainees benefit from a close relationship with the HSPH Department of Biostatistics and the BWH Division of Pulmonary and Critical Care Medicine. More than 85% of our postdoctoral trainee graduates in the past 12 years are active in research, and 68% of them have obtained an NIH K-series grant or similar mentored award.

NIH Research Projects · FY 2025 · 1985-07

PROGRAM SUMMARY/ABSTRACT This continuation of an established program emphasizes the techniques and concepts of cell and molecular biology, genetics, computational biology, developmental and bone biology, and fundamental studies in immunology relevant to rheumatic, autoimmune and musculoskeletal diseases. Population-based clinical research employs rigorous methodological design and statistical analysis. Support is requested for 6 postdoctoral trainees with an M.D., a Ph.D., or both, and 1 predoctoral (Ph.D. candidate) trainee. Faculty are carefully selected and perform research in areas of I) Basic Research including: 1) Adaptive Immunity, 2) Innate Immunity, 3) Bone Biology and 4) Computational Biology, and II) Translational and Clinical Research including 1) Animal Models of Rheumatic and Musculoskeletal Diseases, 2) Human Immunology, Genomics and Genetics, and 3) Patient-Centered Research in the Epidemiology and Outcomes of Rheumatic Diseases. While the primary strength of the program resides in the direct and individual nature of the interaction between trainees and responsible faculty members, substantial didactic experiences, the medical school and university environments, along with a series of structured activities, foster interactions and supplement training. Trainees audit semester courses at Harvard Medical School in their field of basic science, while population science investigators obtain an MPH, Masters, or a similar degree at the Harvard Chan School of Public Health. Postdoctoral trainees in a combined clinical and research training program join this program after completing clinical training. Graduate students join the program only after completing course work and are in Harvard Ph.D. programs in Biomedical and Biological Sciences including 1) Immunology and 2) Bioinformatics and Integrative Genomics. The program is hosted in the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital. Importantly, approximately 40% of faculty are located in other divisions, departments and Harvard Medical School-affiliated institutions and are selected for their relevance to the program goals and their outstanding scientific and training expertise. In addition to Brigham and Women’s Hospital Departments of Medicine, Orthopedics and Neurology, faculty are at 1) the Broad Institute of Harvard and MIT, 2) Boston Children’s Hospital, 3) Massachusetts General Hospital, 4) Harvard Medical School Departments of Immunology, Biomedical Informatics, and Genetics, 5) Harvard School of Dental Medicine, 6) Harvard Chan School of Public Health and 7) UMass Chan Medical School. The program goal is to provide an ongoing pipeline of highly trained and expert investigators prepared for and focused in rheumatic and related musculoskeletal research.

NIH Research Projects · FY 2025 · 1985-07

This is a 5-year renewal application to support 5 postdoctoral trainees for a broad Training Program in Academic Endocrinology. This program has been in place at the Brigham and Women’s Hospital/Harvard Medical School since 1985 and has been highly successful in training physician-scientists and basic scientists, many of whom remain in academic endocrinology. In the last 15-year period, 80% of the 30 trainees who have completed their training remain in a research career. The faculty combines both physician-scientists of the Endocrinology Division with those basic scientists of the Harvard Medical School faculty whose research is significantly related to endocrinology and who have a past and current history of collaborative interactions with Program faculty members in the Endocrinology Division. These 23 faculty members have collectively trained 475 postdoctoral fellows, the great majority of whom remain in research-related careers, either in academic positions or in industry. The 5 trainees appointed each year will be individuals with MD, PhD, or MD/PhD degrees and they will undertake 3-4 years of an intensive research experience with an emphasis on translational investigation. The goal of the program is to provide structured and mentored training experiences to afford trainees with sufficient expertise to apply successfully for mentored research awards, such as K23, K08, K01 or K99 awards, or independent research grants such as R01 grants, to ultimately develop into translational endocrine investigators who will address the great needs for research into endocrine and metabolic disorders that are so prevalent and cause such great morbidity in our society. The diverse areas of research interest of the faculty span endocrine science from the molecular and cellular levels to whole animal, patient-oriented and population levels, encompassing regulation of energy expenditure, insulin signaling, mechanisms of steroid and thyroid hormone action, neuroendocrinology, the control of skeletal muscle development, differentiation, and repair, and the epidemiology of diabetes, obesity, and vitamin D deficiency disorders. There is a strong emphasis on genetics, epigenetics, and new technologies for translating science into therapeutics. Individuals in this program will be trained to translate the insights they gain to develop strategies for the treatment and prevention of common endocrinology- based public health problems, including diabetes, obesity and osteoporosis.

NIH Research Projects · FY 2025 · 1985-07

Abstract Our training program in pulmonary disease and critical care medicine provides comprehensive research training for individuals with a serious commitment to a career in lung biology and biomedical research, particularly as it interfaces with clinical pulmonary and critical care medicine. Lung diseases comprise a major source of excess morbidity and mortality worldwide, so our primary premise is that progress toward improved understanding of the pathobiology of these diseases is required to make progress toward treatment and prevention. The program has a long history (>30 years) of training numerous physician-scientists and scientists who have subscribed to this mission and have become leaders in academic pulmonary and critical care medicine. No changes are anticipated in the program leadership structure. We plan to maintain the previous scientific and training success, while adapting the next generation of researchers to the constantly changing state-of-the-art of basic and translational science. Recent changes have included expanded resources (recruitment of new faculty members, and increased laboratory space) and development of the Brigham Research Institute’s Lung Research Center. This has allowed us to broaden the scope of research questions related to lung biology and attack problems at the most basic and translational levels incorporating new core resources. We have continued to enhance our didactic program and further solidify program organization for oversight and mentoring of trainees. We identify trainees with a demonstrated interest in and commitment to a research career, help them locate a training environment to pursue a problem of interest and in which creative and rigorous thinking combined with state-of-the-art technology is being used to pursue the problem, and provide them with the tools and mindset to attack related problems in the future. Finally, we provide a prolonged period of support so that trainees are prepared to ultimately become productive independent investigators, and future leaders in academic pulmonary and critical care medicine. Of the 40 trainees who have completed the program over the last decade, 38 (95%) remain in academic medicine or research. Moreover, of the 40 trainees who have completed the program, our trainees have been awarded 46 grant awards (Table 8C) consisting of 24 NIH mentorship awards (18 K awards and 6 F32 NRSA), 1 DOD career development award, 3 independent R-awards, 1 Site PI for a UG3, 3 Parker B. Francis awards, and 13 foundation awards (Harvard Catalyst KL2, Pulmonary Fibrosis Foundation, American Heart Association, American Lung Association, LAM Foundation, PCORI, American Thoracic Society, AstraZeneca, Peabody Foundation, and Stork Fund).. In addition, our T32 appointed trainees have published 324 papers with their training grant mentors as co-authors. The Program Director and Associate Program Directors of this training program will continue to work with the utmost enthusiasm and energy to ensure that the trainees will continue to excel and contribute significantly to the academic pulmonary community.

NIH Research Projects · FY 2025 · 1985-07

Project Summary This continuation of an established training program seeks to prepare qualified M.D., Ph.D., and M.D./Ph.D. candidates for academic careers in the field of allergy and immunology. Support is requested for eight postdoctoral trainees having either a M.D. or Ph.D. degree or both. The training program emphasizes three major areas: basic science, translational science, and clinical science. The trainees focused in basic science learn techniques and concepts of immunopharmacology, immunochemistry, and cellular and molecular immunology. Areas of emphasis include the basic biology of mast cells, lipid mediators, dendritic cells, innate lymphoid cells, and animal models of allergic disease. Trainees in translational science paths incorporate informatic approaches to analyze genetic, genomic, and unbiased sequencing or metabolomic data to understand the mechanistic basis of human allergic diseases. Such trainees may also employ bench side approaches to studies using human cells and tissues. Trainees in clinical sciences may focus on epidemiology or clinical trials. The faculty are highly accomplished investigators with extensive mentoring track records and substantial extramural grant support. The three-year research training period is designed so that each trainee learns a range of techniques and approaches, gains a broad understanding of the innate and adaptive immune host responses, and establishes a template for an early career research focus. This time frame also permits the trainee, along with his or her mentor and Scholarship Oversight Committee, to plan for post-fellowship career development, with the goal of defining a path in academia that is commensurate with the trainee’s developing skills and interests. The research experience is enhanced by didactic course work, as well as workshops in grant writing, manuscript composition, and lab management. The program continues to be highly successful, with over 75% of the graduates in the past decade having full-time academic appointments, many of whom are primarily research based with independent NIH support.

NIH Research Projects · FY 2025 · 1985-07

SUMMARY The Cardiovascular Research Training Program at Brigham and Women's Hospital aims to prepare trainees for independent careers in investigative pursuits. The three themes of particular focus for this T-32 program include 1) Myocardial Cellular and Molecular Biology and Genetics, 2) Vascular Cell and Molecular Biology, and 3) Translational/Clinical Cardiovascular Research. We propose to strive to continue our record of preparing our trainees to develop independent research programs, obtain faculty positions, and acquire peer- reviewed funding. Our past trainees (88%) continue to focus on research with faculty academic appointments or via research and leadership positions in industry. 42% have been awarded career development grants (K- award or equivalent). Our environment offers substantial resources to trainees, ranging from core laboratories within Brigham and Women's Hospital, formal educational opportunities including those of the adjacent Chan- Harvard School of Public Health, and ample resources within the individual laboratories of faculty members. The program provides a structured program for each trainee including formulating formal Individual Development Plans for each trainee, orientation lectures, formal instruction in responsible conduct and professionalism in research, advanced course work, multiple inter-disciplinary research group meetings and seminar series, and tailored and flexible research experiences. Indeed, a historical strength of our T-32 program is working with trainees to place them in the best laboratory and mentoring environment to meet their individual training needs and career goals whether it be at BWH and its partner institution the MGH, or in the broader surrounding environment including the Harvard Medical School and Chan School of Public Health, The Broad Institute, Children’s Hospital, the Dana-Farber Cancer Institute, MIT, the Harvard BioLabs and the Stem Cell Regenerative Biology Institute among others. Each trainee works under the close supervision of a faculty mentor throughout their training. In addition, a Fellowship Advisory Board, including an External Advisory Board, oversees the program and monitors closely the progress of trainees and their Individual Development Plans. The Research-in-Progress seminar, an annual Fellow's Poster Session, and Cardiovascular Grand Rounds serve to highlight and support the work of the post-doctoral trainees. We have a particular and successful commitment to recruiting and fostering the careers of woman and minority trainees. In this renewal application we propose to continue our longstanding record (documented within) of preparing a talented pool of fellows for successful academic careers.

NIH Research Projects · FY 2026 · 1984-09

Acute kidney injury (AKI) remains a very important and growing unmet therapeutic need. The overall goal of the studies proposed in this competitive renewal application for a grant which is now in its 37th year of support remains to understand the mechanisms involved in kidney cell injury and repair in order to develop therapeutic strategies for the prevention and treatment of AKI and its chronic consequences. The current proposal builds on prior work establishing the role of proximal tubule cells (PTCs) in adaptive and maladaptive repair. We hypothesize that kidney PTC cell injury results in DNA damage which triggers a DNA damage response including breast cancer 1 susceptibility protein (BRCA1), bromodomain containing protein 4 (BRD4) activation and nuclear lamin A accumulation leading to arrest of the cell cycle, inhibition of cell death and a senescence associated secretory phenotype (SASP). The released chemokines and growth factors, including hedgehog proteins, then activate COUP-TFII in the pericyte/fibroblast by a BRD4-dependent process, converting them to activated myofibroblasts. Male and female PTC specific BRCA1 and lamin A knockout mice, wild-type male mice and a novel transgenic “ICE” mouse with inducible DNA damage will be used in models of ischemic, obstructive and toxic kidney injury. Animal studies including genetic modifications with selective knockdown of BRCA1 or lamin A expression in PTCs or COUP-TFII in fibroblasts will be complemented by inhibitor studies and human kidney organoids, tubuloids and spheroids to enable the study of mechanisms of injury and maladaptive repair in human cell systems ex vivo. In Specific Aim 1 we will define the roles of PTC BRCA1 and BRD4 in maladaptive repair. We will evaluate pathways leading from DNA damage to senescence, impaired cell death, Target of Rapamycin (TOR)-Autophagy Spatial Coupled Compartments (TASCC) generation, and generation of pro-fibrotic growth factors and chemokines which lead to CKD. We will also evaluate the role of BRD4, a member of the bromodomain and extraterminal (BET) family, to stabilize BRCA1 after injury, increase senescence and inhibit death of DNA damaged cells. In Specific Aim 2 we will define the role of PTC lamin A in the pathobiology of kidney senescence and fibrosis. Assess the effects of lamin A and ZMPSTE24, which converts prelamin A to mature lamin A, on PTC senescence and tissue fibrosis in response to injury in vivo, and explore cellular mechanisms using human kidney epithelial cells, kidney organoids, and tubuloids ex vivo. In Specific Aim 3 we will evaluate the role of COUP-TFII, BRD4 and senescence on activation of fibroblasts, enhancement of glycolytic metabolism, and generation of profibrotic mediators.

NIH Research Projects · FY 2025 · 1980-09

The Harvard Medical School Department of Dermatology T32 training grant has been active for more than 45 years, and over that period of time has trained many postdoctoral fellows who have become national leaders in dermatology. Dr. Thomas Kupper has served as Principal Investigator since 2000. There are three Harvard-appointing Dermatology departments: the Beth Israel Deaconess Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital. An executive committee comprised of the chairs of these departments oversees the Harvard combined residency program, and provides advice and counsel to Dr. Kupper with regard to the T32 grant. The training grant has two overarching goals. The first is to identify, recruit, and support promising dermatologist physician scientists interested in a career in biomedical research. While such candidates most often come from Harvard's Dermatology Residency program, trainees from other dermatology residencies are eligible as well. The second goal is to support the development of outstanding PhD scientists who are interested in a research career in investigative dermatology and related fields. Considering the past decade of the training grant, all 30 of our trainees continue to be involved with biomedical research, whether in academic medicine or biotechnology/pharmaceutical companies. This group of 30 trainees has authored 173 peer-reviewed manuscripts over the past decade, with a mean impact factor of 7.9. Over the past decade, T32 graduates have successfully competed for extramural funding as PI's, including National Institutes of Health K23, K12, K08, and DP5 awards (from the Office of the NIH Director); applications for K99/R00 and K08 grants are pending. For the next funding cycle, we have retained our External Advisory Board consisting of eminent academic dermatologists and scientists who will assist with choosing candidates and evaluating progress. It remains our conviction that Training Grant support for biomedical scientist postdoctoral fellows interested in skin disease research has never been more critical to their careers, and by extension, the long-term survival of academic investigative dermatology.

NIH Research Projects · FY 2025 · 1979-07

Project Summary/Abstract The proposed Training Grant in Genetics is the centerpiece in efforts to provide postdoctoral research training in medical genetics in the Harvard Medical School (HMS) Genetics Training Program (HMSGTP) with an overall goal to train future academic leaders of this discipline. The requested number of trainees per year is eight, and these individuals comprise physicians and Ph.D.s undertaking medical genetics research. Physicians will join the training program largely with experience in a variety of medical specialties, having done residency training in a relevant discipline or enrolled in ACGME combined residency programs with medical genetics and genomics (MGG). Ph.D.s may be appointed after completing training in ACGME MGG laboratory specialties or training in laboratories pursuing foundational research in human genetics. The ACGME programs may lead to ABMGG board certification. Advances in genetics and genomics, in particular the sequencing of the human genome, have dramatically accelerated the pace of research in this area. Genetics and genomics are currently major drivers of medical research and are leading to advances in diagnosis and treatment of both rare and common disorders. Implementation of the many advances in genetics requires a well-educated, diverse and talented workforce of genetics professionals. This Training Grant in Genetics has made possible training of physicians and scientists in a wide variety of topics in medical genetics, enabling them to take advantage of the extraordinarily rich academic environment present at HMS and its affiliated institutions as well as the greater Boston scientific community notably including the Broad Institute. In addition, it has served to promote interactions between medical geneticists and investigators and provided a forum for increasing faculty contact with trainees in didactic sessions. Training laboratories of the HMSGTP have historically been centered now for five decades at HMS and its affiliated institutions including Brigham and Women’s Hospital (BWH), the HMS Department of Genetics, Beth Israel Deaconess Medical Center (BIDMC), Boston Children's Hospital (BCH), Dana Farber Cancer Institute (DFCI), and Massachusetts General Hospital (MGH), and also include laboratories at Massachusetts Institute of Technology (MIT) and the Broad Institute. Since the last renewal of this training grant, an ever enlarging variety of opportunities in genomic medicine have developed to enhance the focus of training in medical and human genetics, and the program is fully integrated in HMSGTP, accredited by the ACGME in Clinical Genetics and subspecialties of Medical Biochemical Genetics and Molecular Genetic Pathology and combined training with Clinical Genetics leading to dual board certification (Internal Medicine/MGG, Pediatrics/MGG, Maternal-Fetal Medicine/MGG, with an application underway for training in Reproductive Endocrinology and Infertility/MGG), Clinical Biochemical Genetics and Laboratory Genetics and Genomics, providing the opportunity for trainees to become active candidates for certification in a discipline(s) of medical genetics in addition to receiving research training for two to three years.

Other NSERC · FY 2024