Washington University

NIH Research Projects · FY 2025 · 1988-07

The decrease in the number of physician-scientists has been widely recognized as a major threat to biomedical research, and there has been an even more dramatic decrease in the number of surgeon-scientists. The Department of Surgery at Washington University School of Medicine is one of the nation's leading academic surgery departments and is currently ranked #2 in NIH funding by the Blue Ridge Medical Institute. The Department has a strong and uncompromising commitment to training academic surgeon-scientists. The Surgical Oncology Basic Science and Translational Research Training Program is a critical component of this overall training goal. NCI support will provide a meritorious cadre of up to eight surgical trainees from general surgery and other surgical subspecialties the opportunity to develop essential skill sets in basic science, translational, and/or public health research. The Surgical Oncology Research Training Program has evolved in parallel with a dynamic training environment at WUSM, and currently takes advantage of unique resources in the Department of Surgery, Siteman Cancer Center, the Department of Surgery's Division of Public Health Sciences, and the Institute of Clinical and Translational Sciences to develop customized and highly structured formal didactic and mentored research experiences for individual T32 Program Scholars. The success of the Program is demonstrated by the long-term success of T32 Program Scholars in academic surgery. 24 of 32 Scholars (75%) who have completed the Program and clinical training in the last fifteen years remain in academic medicine, significantly better than published metrics (16-44%). Similarly, 7 of 32 Scholars (22%) who have completed the Program and clinical training in the last fifteen years have independent research funding, significantly better than published metrics (1.0-2.5%). The Surgical Oncology Research Training Program continues to evolve. Changes include changes to the program leadership, development of two distinct research tracks (basic science track, and translational research/public health/clinical effectiveness track), development of program-specific Work-in-Progress and Professional Development Seminar Series, and a formal mentoring training program. These changes will ensure that the Surgical Oncology Research Training Program will continue to maintain excellence at the forefront of two different surgical oncology research paradigms, basic science research, and translational/public health/clinical effectiveness research. The WUSM General Surgery residency is ranked #5 in the nation, and we have an outstanding applicant pool. NCI support will allow WUSM to continue to provide the next generation of surgeon-scientists with the research training required to succeed in an increasingly competitive research environment.

NIH Research Projects · FY 2025 · 1986-07

PROJECT ABSTRACT This revised application seeks renewal for years 36-40 of a T32 program that will provide training for 7 postdoctoral MD, PhD or MD/PhD scientists. The training program is centered in the Department of Pathology and Immunology (P&I) at Washington University in St. Louis, and consists of 36 training mentors who are housed in 10 different departments. The training faculty consists of 16 women and 20 men and includes 2 URM. The faculty are a highly interactive group of immunologists with interests in cancer immunology and cell/molecular cancer biology and are led by a director and associate director who are well known for their contributions to cancer immunology/immunotherapy and their commitment to training of young scientists. The research of our faculty focuses on various aspects of cancer immunology and immunotherapy with an emphasis on the molecular basis of cellular activation and suppression. A Steering Committee of six T32 faculty members oversees the training program and is responsible for the selection and oversight of the trainees. We also formed a new external advisory board to obtain outside opinions on our T32 program. Training includes a 2-to 3-year period of full- time laboratory research, where the trainee is exposed to the latest approaches in cancer immunology and cell and molecular cancer biology. The training also includes presenting at laboratory meetings, participation in weekly seminars and yearly retreats, training in research ethics and rigor and reproducibility, participation in national/international meetings and opportunities to audit advanced courses in Immunology, Cell Biology and Cancer Biology. During the most recent 10-year funding period of this T32, 49 trainees were supported by the Program: 4 withdrew for personal reasons and 7 trainees who had just started the program had their work delayed by the COVID-19 pandemic. The remaining 38 trainees published 171 papers with 33 papers appearing in high impact journals and 76% of these trainees had at least one first-author paper. Of the 70 trainees who have been or are supported by this Program in the last 15 years, 66 (94%) have remained in research. These demographics document the success of our T32 Training Program and provide strong support for its competitive renewal.

NIH Research Projects · FY 2025 · 1983-08

Project Summary Our goal is to elucidate the mechanisms by which mitral regurgitation (MR) creates substrates for arrhythmias, both atrial and ventricular, and to identify targeted interventions. Valvular heart disease is the most common etiology of chronic atrial fibrillation (AF). Prospective, randomized trials have shown that surgical ablation is highly effective in restoring normal sinus rhythm in patients with mitral valve disease and there is clear evidence that it provides a survival benefit. Newer studies have shown that ventricular remodeling and arrhythmias following MR increase the risk of sudden cardiac death, especially in young women. In the previous cycle of the grant, we refined a canine open chest model of MR via chordae avulsion previously developed in our laboratory into a minimally invasive model that better mirrors the clinical picture. In our clinical practice, we treat MR patient with and without AF, and are able to characterize their cardiac anatomy and electrophysiology with delayed-enhancement MRI (DE-MRI) and electrocardiographic imaging (ECGI), respectively We propose to characterize the remodeling of the atria and ventricles following MR in our canine chordae avulsion model and in patients. As our preliminary data suggest an inflammatory-mediated mechanism, we will identify patterns of immune cell infiltration that correspond to anatomical and electrophysiological changes to facilitate the development of novel therapeutic strategies. We propose the following specific aims: Specific Aim 1. Define the anatomical and electrical substrates for AF and ventricular arrhythmias in a chronic canine model of MR. The anatomical substrate will be characterized using echocardiography and DE-MRI, the electrical substrate using in-vivo plaque mapping, optical mapping, and ECGI. We will obtain activation maps of the heart, including the most arrhythmogenic parts of the atria (the LAPW) and the ventricles (periannular region and papillary muscles) and correlate them with fibrosis as defined by DE-MRI. Specific Aim 2. In our canine MR model, we will determine if inflammatory leukocyte infiltration precedes remodeling following MR induction and whether its presence corresponds to changes in electrophysiology. We will perform single nuclear RNA (snRNA) analysis of the LAPW and correlate it with LAPW electrophysiology characterized in thin slices at baseline, 4 weeks, and 6 months after MR induction. In the ventricle, snRNA analysis of the mitral periannular region and papillary muscles at the same time points will be correlated with local electrophysiology. Specific Aim 3. Define the atrial and ventricular electrophysiological remodeling in MR patients with and without AF referred for surgery. ECGI will be used to detect changes in the atrial and ventricular activation sequences and to detect premature ventricular contractions. Electrical remodeling will be correlated with fibrosis and fiber orientation as well as atrial and ventricular volumes as determined by DE-MRI.

NIH Research Projects · FY 2026 · 1982-01

ABSTRACT Acute malnutrition (wasting) affects >45M children under the age of 5; two-thirds suffer from moderate acute malnutrition (MAM) while the remainder have severe acute malnutrition (SAM). Besides accounting for 21% of life-years lost among children younger than 5 years, undernutrition leads to long term growth impairments, immune and metabolic dysfunction, and altered CNS development. Current treatments have limited effectiveness. We found that MAM and SAM are associated with impaired gut microbial community development (microbiota immaturity). We then screened Bangladeshi complementary foods in gnotobiotic animals for their capacity to improve the fitness and expressed beneficial functions of key growth-promoting bacterial taxa underrepresented in the microbiota of children with malnutrition. This yielded a `microbiota- directed complementary food' formulation (MDCF-2) that in a randomized controlled clinical trial (RCT), repaired the microbiota of 12-18-month-old Bangladeshi children with MAM and accelerated weight gain/ameliorated stunting compared to an existing ready-to-use supplementary food (RUSF) that was 15% more calorically dense. The efficacy of MDCF-2 was confirmed in a second RCT. We identified metabolic pathways in metagenome-assembled genomes (MAGs) belonging to specific strains of Prevotella copri that are differentially expressed in response to MDCF-2 and positively associated with growth (weight-for-length Z score; WLZ); this differential expression was associated with the metabolism of specific glycan structures in MDCF-2 and with the magnitude of clinical response to treatment. Tests of MDCF-2 derivatives in which single ingredients were replaced by `glyco-equivalent' food staples, conducted in gnotobiotic mice harboring MAM- donor microbiota, followed by a pilot translational study in Bangladeshi children with MAM, further highlighted glycan structures targeting P. copri. We will use 2 specific aims to build on these findings. Aim1-Perform a pan-genome analysis to define features of P. copri MAGs positively associated with WLZ in our RCTs that are highly conserved in P. copri strains we culture from Bangladeshi children, and strains obtained from other countries. Combine in vitro growth assays, microbial RNA-Seq and mass spectrometry to test the effects of lead glycan structures obtainable at scale singly and in combination, on cultured P. copri strains with carbohydrate utilization machinery exemplifying the different strains documented in the pan-genome analysis. Results will identify strains/glycan combinations that approximate the MAG expression profiles observed in our RCTs and gnotobiotic models and refine selection of prebiotic candidates. Aim2-Use a gnotobiotic mouse model of intergenerational microbiota transmission to perform mechanistic studies (microbial RNA-Seq/host bulk and snRNA-Seq/microbial community and host targeted MS-based metabolomics) of the effects of prebiotic single or combination glycan leads from Aim1 on targeted P. copri strains and on host growth and expression of metabolic/signaling pathways in intestinal cell lineages distributed along the length of the gut.

NIH Research Projects · FY 2025 · 1980-09

PROJECT ABSTRACT This is an application to renew the Infectious Diseases/Basic Microbial Pathogenesis Training Grant from Washington University. With the advent of generally available antibiotic therapy about 50 years ago, many physicians and scientists predicted the end of infectious diseases as a major area of health concern. Subsequent events have proven this prediction wrong, and the past decades have seen the emergence of many newly identified infectious diseases, including Lyme Disease, erlichiosis, SARS, COVID-19, West Nile encephalitis, chikungunya, MERS, ebola and HIV. The reemergence of old infectious diseases, such as malaria and tuberculosis, in more virulent and more antibiotic resistant forms also has increased public attention on the health problems posed by infectious diseases. It is rare that a week goes by without some troubling headline concerning new infectious disease outbreaks. Thus, far from gradual disappearance as a health concern, infectious diseases have emerged as being of increasing importance to the health concerns of the nation. The emerging antibiotic resistance of current pathogens and the rise of new disease agents have made clear the necessity of increased fundamental scientific investigation into all aspects of infectious diseases. The purpose of the Washington University Training Program in Infectious Diseases/Basic Microbial Pathogenesis is to help fulfill this need by recruiting promising young investigators to this field and training them in outstanding research programs with preeminent investigators who collaborate across multiple disciplines (or who function in interdisciplinary teams) to perform infectious disease research. Our Training Program, which has had NIH support for the past 40 years, integrates faculty from four departments: Medicine, Pediatrics, Molecular Microbiology and Pathology & Immunology. The program provides training to M.D., Ph.D., and M.D./Ph.D. postdoctoral fellows, and to Ph.D. and M.D./Ph.D. students, in disciplines related to pathogenesis and host defense in Infectious Diseases. The laboratories of the program preceptors use tools of molecular biology, biochemistry, genetics, genomics, immunology, cell biology and translational medicine. Thus, the program trains young investigators to be able to answer the important questions of microbial pathogenesis, from studies of basic biology through application to the bedside.

NIH Research Projects · FY 2025 · 1978-07

The Washington University Program in Principles of Pulmonary Research provides multidisciplinary training for predoctoral and postdoctoral scholars committed to a career in pulmonary research. The aim of the Program is to prepare individuals for a career in academic pulmonary medicine through rigorous research training to address problems in lung biology and disease. The predoctoral portion of the Program engages PhD and MD-PhD students in the graduate school by direct connection to experts in lung biology. The postdoctoral portion of the Program enables MD and MD-PhD physicians who are training in clinical pulmonary and critical care medicine to learn state-of-the-art scientific research, in concert with PhD trainees from a basic science background. The Program funds seven postdoctoral and five predoctoral trainees for 2-3 years of support before they transition to additional career development awards. Trainees and mentors are selected to represent many interests, skills, and experiences. The Program and its trainees are closely monitored through a multi-director (PD) approach and advisory committees (Program Review, Mentoring, Internal Advisory, and External Advisory). The success of the program is driven by an individualized training approach with frequent points of contact between the MPIs, trainees, and preceptors, toward a set of trainee core competencies. Progress is monitored by bidirectional evaluations between trainees and preceptors, with input from advisory committees. Research skills are developed in one of three interdisciplinary research tracks: two basic-translational pillars (Immunology-Host Defense, and Molecular-Cell Biology) and a Clinical-Translational Sciences pillar. The clinical pillar extends these basic science strategies to human subject research. The approach provides a multidisciplinary, collaborative, and synergistic plan for research training by bringing together a group with broad expertise. For all trainee activities within this structure, there is a carefully constructed mentoring process that includes competency-based milestones for trainee presentation, publication, and grant application. To achieve these goals, predoctoral and postdoctoral training efforts are discussed at a weekly Pulmonary Research Conference. The Conference is the hub for input from an overall Program Review Committee (that includes the PDs and their advisors) and a project-specific Advisory Committee (that includes the trainee’s mentors and collaborators). Trainees also receive input via individual lab and group meetings and additional research conferences. The research-intensive experience is supplemented through graduate coursework (including a Master of Science) to build specialized skills and mandatory training in the Responsible Conduct of Research. A set of workshops and retreats stress communication skills, grantsmanship, mentoring, and teaching skills. Together, these mechanisms serve to ensure high-level multidisciplinary trainee experiences and performance in previous and present cycles of this longstanding, highly successful Program that has positioned numerous leaders in lung disease across the United States.

NIH Research Projects · FY 2025 · 1978-07

ABSTRACT This renewal application seeks continued support for years 45-50 of the Washington University Training Program in Immunology. This renewal application refines the training program to take opportunities to address emerging needs and challenges in training of predoctoral and postdoctoral trainees. Washington University School of Medicine (WUSM) has been a major center /magnet for both research and training in immunology over many decades. The Immunology community at WUSM has achieved a world-recognized status, including 5 members of the National Academy of Sciences. It is characterized by a collaborative atmosphere that has helped establish an excellent environment for training young Immunologists. This T32 training has been a central component within this community, and has developed a symbiotic relationship that benefits the trainees and mentors alike. In this renewal application, we have kept those parts that have historically worked exceptionally well, and have also sought to address what we see as emerging challenges in obtaining a training toward becoming a leader in immunology research. The needs we see are a result of the ever- increasing amount of information, which has gradually led to a significant challenge for young trainees to master, in the short time allotted before the pressures of independent research and discovery in mentor's lab become the paramount motivation. Further, this application addresses questions from past reviews and refines the distinction between activities of predoctoral and postdoctoral trainees supported by this T32 training program and other trainees of the larger graduate program in immunology at WUSM. In this renewal, we have seen this as a positive opportunity to revise the specific training provided by this T32, through our creation of a new curriculum specifically tailored to providing a structured environment that ensures the trainee to obtain a broad and in depth mastery of basic immunology. We are requesting the continuation of the 6 predoctoral and 4 postdoctoral trainee slots per year. This successful Training Program is thus producing the next generation of basic and clinician scientists, whom we expect will elucidate the intricacies and mechanisms of our immune system functions, and thereby help develop novel therapeutic strategies for multiple human diseases.

NIH Research Projects · FY 2025 · 1977-09

PROJECT SUMMARY/ABSTRACT This application is the competitive renewal of the “Immunobiology of Rheumatic Diseases” Training Program at Washington University School of Medicine. The program, which was initiated in 1977 by Dr. John Atkinson, has a strong record of training postdoctoral fellows who are committed to careers in rheumatic disease research. The goal of the training program is to develop independent scientist who will ultimately work to improve outcomes of patients suffering from rheumatic diseases. The current application, which seeks support for five MD, MD/PhD, or PhD postdoctoral trainees per year, incorporates a number of new programmatic features to enhance this training mission. The Program accepts trainees from an expanded pool of outstanding applicants and benefits from close relationships to the Physician Scientist Training Programs in both Medicine and Pediatrics, the Institute of Clinical and Translational Sciences, and the Division of Biology and Biomedical Sciences. New to this competitive renewal is the offering of a clinical/translational research track which complements our basic science research track. Trainees will benefit from extensive didactic offerings leading to a Master of Science in Clinical Investigation degree. The centerpiece of either track remains an intense mentored research experience. Trainees are mentored by a committed primary faculty mentor, in collaboration with their scholarship oversight committee. The talented group of 35 well-funded faculty mentors are organized into four thematic areas- Immune Regulation and Host Defense, Animal Models of Rheumatic Disease, Clinical/Translational Research, and Omics. These preceptors are a major strength of this grant. The uniquely collaborative environment among the faculty preceptors and at WUSM provides an ideal setting for the professional development of the trainees. Hands on workshops, research seminars and programs in the Responsible Conduct of Research complement the four thematic areas.

NIH Research Projects · FY 2025 · 1977-03

PROJECT SUMMARY/ABSTRACT This competitive renewal is to continue the Aging and Development Training program in the Department of Psychological & Brain Sciences at Washington University. As the population of the US and many other countries shifts toward an older distribution, the scientific and societal challenges of human aging continue to increase. There is a critical need for researchers with a firm foundation of training in the behavioral and psychological characteristics of aging, and for these researchers to have the cutting- edge skills to integrate neurobiology, genetics, and socioemotional mechanisms of aging into their work. This renewal builds on the program's unique role as a pipeline of aging researchers with a rigorous training in psychological science, while building transdisciplinary bridges. With this renewal a core group of 20 Faculty in the Department are joined by 13 faculty with primary appointments in the Medical School, the Brown School of Social Work, and the McKelvey School of Engineering to serve as program mentors. Training is organized around four interrelated themes: cognitive changes in aging, the cognitive neuroscience of aging and dementia, personality and socio- emotional aging, and translational impact. Trainees will receive in-depth training in one to two themes and broad exposure to the others. The program trains both clinical and non-clinical PhD students, and postdoctoral fellows. Trainees benefit from the excellent resources in the Department and across the University, including those of the Charles and Joanne Knight Alzheimer Disease Research Center and the Harvey A. Friedman Center for Aging. In this proposal we document the high quality of the program trainees and faculty, the structure of its well-established training program and its assessment, and the program's track record of success.

NIH Research Projects · FY 2025 · 1975-07

Project Summary/Abstract This application is for the competitive renewal of the “Principles in Cardiovascular Research Training Program” at Washington University School of Medicine. Since its inception in 1975, this training program has demonstrated a strong track record of training physician-scientists and scientists who have emerged as thought leaders in Cardiovascular Medicine. The primary objective of this training program is to provide multidisciplinary research-based training opportunities, incorporating diverse areas of focus and investigative modalities to develop independent scientists who are trained to utilize basic, translational, clinical, and/or health services-focused cardiovascular research principles to improve outcomes of patients with cardiovascular disease. The re-designed program is focused on training the next generation of physician- scientists to tackle the resurgence in cardiovascular diseases triggered by the epidemic of obesity and metabolic syndrome, while ensuring a continued focus on current cardiovascular disease landscape to address areas of unmet need. The program is housed in an intellectually stimulating and scientifically creative environment within the Cardiovascular Division and Center for Cardiovascular Research, and benefits from highly collaborative interactions between 28 faculty mentors that hold appointments in 2 Schools, 8 Departments and 4 Divisions in the Department of Medicine. The faculty are well funded; have been recruited based upon their multidisciplinary expertise in the six area of focus, namely myocardial biology, inflammation, vascular pathobiology, ion channel biology, metabolism and genomics, with health care economics and policy as a unique area of training focus integrating the clinical and services aspects of cardiovascular health; and demonstrate a strong track record of mentoring. The program objectives are unique as compared with other training opportunities available within the institution. The current application, which seeks support for 6 MD, MD-PhD or PhD post-doctoral trainees per year, incorporates many new programmatic features developed to enhance the training mission and is designed to provide 2-3 years of uninterrupted research training after completion of core clinical requirements. The curriculum has been re-designed to focus on the major research themes, with emphasis on Rigor and Reproducibility and Responsible Conduct of Research; and a team-based approach is encouraged with co-mentoring to enhance interdisciplinary training opportunities. The cornerstone of training is a rigorous trainee-driven project supervised closely by experienced faculty mentors. Trainees participate in the weekly Trainee Research Seminar series and the Cardiovascular Research Seminars series, as well as our annual Cardiovascular Research Day Symposium. Training is monitored by formal mentoring committees; and informal support networks exist to guide trainees towards competing for career development awards with goal of developing into independent cardiovascular researchers. Steering and External Advisory Committees are in place to monitor the Program for its effectiveness in achieving Program objectives.

NIH Research Projects · FY 2025 · 1975-07

The overarching goals of the Washington University T32 Program in Academic Gastroenterology are to train, nurture and develop academic physicians and physician-scientists (MD and MD/PhD trainees) for productive and sustaining careers as bench or clinical translational investigators, scholarly and institutional leaders in the broad field of digestive and liver diseases. This Program offers structured opportunities for two postdoctoral trainees per year (4 trainees total) for mentored training in either laboratory-based scientific discovery (Track 1), or alternatively in defined areas of clinical translational research, including disease prevention, health disparities, quality outcomes, public health and epidemiology (Track 2). After successful introduction during the current grant cycle, we seek to continue support for two predoctoral slots per year, to recruit members of the graduate student and MSTP community into scientific careers in digestive and liver disease. These overarching goals, reflected in the Rigor of Prior Research, are realized through intensive and sustained interactions with 34 participating faculty (21 Track 1; 13 Track 2), individualized programs of research program design, dedicated planning and career guidance with targets for progressive academic development, supplemented where appropriate by course work and guided study leading to Masters degrees in Clinical Investigation or Population Health Science for postdoctoral trainees and the PhD degree for predoctoral trainees. Our specific aims for the current proposal include: 1) Maintain a rigorous recruitment and selection process that integrates clinical and research training with career guidance to sustain a legacy of producing scholarly, research-focused MD and MD/PhD gastroenterologists. 2) Develop an exceptional pipeline of predoctoral students who will pursue research in digestive and liver research and advance the field. 3) Create a supportive, responsive, and flexible administrative structure to attract and nurture the most exceptional trainees. 4) Provide a structured training environment with the flexibility to accommodate individualized programs of research training, mentored academic career guidance and support, including continued comprehensive training in the ethical conduct of research. 5) Encourage and support postdoctoral trainees to obtain advanced degrees in Clinical Investigation or Public Health and to obtain formal training where needed in basic and/or applied clinical sciences. 6) Continue a vigorous external speaker series through partnership with Division and DDRCC seminars and visiting professor engagements that will offer trainees the opportunity to interact with thought leaders as well as encouraging collaborations and scientific interaction. 7) Devise and implement career development programs tailored to enhance the transition of trainees to junior faculty status, whether at Washington University or at another academic institution. 8) Evaluate and modify the curriculum in response to trainees’ needs, reflecting changes in the health care and funding climates with continuous quality improvement processes.

NIH Research Projects · FY 2025 · 1975-07

The long-term objective of this competitive renewal application is to train exceptional diabetes scientists capable of leveraging the latest research tools to decrease suffering from diabetes. The program trains MD, PhD, and MD PhD scientists for 2 to 3 years through mentored research and structured activities that are seamlessly integrated with basic science departments, clinical departments, and centers in the context of considerable institutional support. It is the only T32 program at Washington University focused on diabetes. Continually evolving in response to self-assessment and external reviews, the training program features strengths that include: A) Research facilities and a research environment encompassing the Institute of Clinical and Translational Sciences (Washington University CTSA), the NIDDK-supported Diabetes Research Center (DRC) and Nutrition Obesity Research Center (NORC), as well as extensive additional resources. B) A required core curriculum in diabetes science in addition to required supplemental courses that include training in Rigor and Reproducibility and in the Responsible Conduct of Research, provided at no cost to trainees. C) Administrative support to facilitate interdisciplinary and multidisciplinary research training. D) Addition of a third program director with expertise in beta cell biology and mentoring to complement two successful program directors with strong training records and extensive research backgrounds, all with significant commitment of effort. E) 35 preceptors focused on diabetes and related metabolic diseases. Over the past 10 years, this group has trained >320 postdoctoral fellows of whom 84% have continued in research. Each of the mentors participates in one or more components of this training program, and this group has considerable external research support (average current year support ~$1,134,257/preceptor). F) New required mentoring training adopted in response to program evaluations. G) Highly competitive pools of PhD and clinical degree trainees. All available postdoctoral positions have been filled over the past 15 years and the program completion rate is 93%. H) Anonymous feedback from current and former trainees indicating substantial satisfaction with the training program over the most recent funding period. I) Successful training record in terms of publications, competing for grant support, and remaining in research or research-related careers. J) An integrated short-term research program for medical students coordinated through the Washington University DRC. Overall, this training program prepares a talented group of scientists across the translational spectrum to exert a sustained influence on research in diabetes and related metabolic diseases.

NIH Research Projects · FY 2024 · 1975-07

Enter the text here that is the new abstract information for your application. The Washington University Medical Scientist Training Program at Washington University in St. Louis was established in 1969, and has been continuously funded by the NIH since 1970. It has trained 658 MD-PhDs, more than any program in the nation. As it has been since the program's founding, our primary goal is to identify, train, and mentor students who will become leaders biomedical research, patient care, and medical education. To that end, we have designed a flexible, individualized training pathway that emphasizes the integration of clinical and research training. The University's substantial commitment to the program is evident not only in providing 68% ($8.6 million in FY2018) of the total MSTP budget, but also in tailoring the curriculum and policies to accommodate the unique requirements of MD-PhD training. Appointments to this T32 are typically made for the first 3 years of training. We are able to leverage each of the grant’s 44 training slots by a factor of 4.4 through university and other funds, which allows us to support a current population of 192 students. To select individuals to train in the program, we focus primarily on academic achievement, research experience, and commitment to a research career. Students typically train in the Division of Biology and Biomedical Sciences, a trans-university consortium of 11 doctoral programs, but a significant number train in other academic units, including Biomedical Engineering. The 156 training faculty for this proposal are out of a total population in these academic units of over 570 tenure-track faculty. Policies are in place to select faculty for participation in graduate training, and training faculty are reviewed every 5 years. Our program enjoys strong interactions with other programs at Washington University for training of physician-scientists after they receive their doctorates, i.e., Physician-Scientist Training Programs (PSTPs) in our clinical residency and fellowship programs. Student attrition is low and has declined significantly over the past 10 years. Time to degree has stabilized at 8.0 years, and is lower than the national average. Outcomes data show that 78% of those who have completed postgraduate training are employed by academic institutions, research institutes, federal agencies, and biotech or pharmaceutical firms. Many have research support from the NIH or other sources, and some have leadership roles in other MD-PhD programs. While our program has had a long history of success, we are cognizant of the future challenges facing our trainees to achieve success in careers as physician-scientists involved in basic and translational research. To help them reach the highest levels of success, our goals for the next 5 years include: 1) Providing our trainees with academic programs that integrate basic science with clinical medicine; 2) Providing our trainees with a new career mentorship program that features successful physician-scientists; 3) Building on existing programs to enhance camaraderie and instill confidence that the physician-scientist pathway is viable and worthwhile; 4) Working with our PSTP colleagues to further enhance the likelihood of success of our students; 5) Working with our institutional stakeholders to reduce time to degree without sacrificing necessary rigor, and 6) Building on our recent successes in recruiting outstanding individuals who will be well trained to be leaders in the discovery and application of ground-breaking research and innovative patient care.

NIH Research Projects · FY 2025 · 1975-07

Although advances in hematology have led the way in many fields of basic and translational biomedical research, hematologic diseases remain major threats to public health. For example, the prognosis for many hematologic malignancies continues to be poor. Current treatments are inadequate to support a normal lifestyle for most patients with sickle cell disease. In the U.S., at least 500,000 venous thromboembolic events, 1 million heart attacks and 150,000 stroke deaths occur each year. At the same time, opportunities for hematology research have never been more promising, and converting these opportunities into medical advances will depend upon training the next generation of basic and translational hematology researchers. The Molecular Hematology train- ing program proposes to fill this need for 5 predoctoral and 8 postdoctoral trainees per year. Predoctoral Ph.D. and M.D./Ph.D. students follow the curriculum of the Washington University graduate school. After passing their qualifying examination, they enter the laboratory of participating faculty Mentors for 3-4 years of laboratory re-search to complete their dissertation. Postdoctoral Ph.D. trainees from around the world apply to participating laboratories; postdoctoral M.D. and M.D./Ph.D. trainees usually have completed the clinical training component of a Hematology-Oncology fellowship program at Washington University or elsewhere. The duration of postdoc-toral training depends on prior experience. Those with Ph.D. or M.D./Ph.D degrees typically conduct research for 2-3 years before transitioning to an independent research position, whereas those with an M.D. degree may benefit from 3-4 years of postdoctoral training. Trainees receive intensive mentoring and career counseling, and participate in coursework, journal clubs, and seminars. The major facilities of the program consist of ~80,000 square feet of fully-equipped laboratory space that house the Divisions of Hematology and Oncology, as well as extensive institutional resources for genome sequencing, immune monitoring, informatics, animal studies, and patient-oriented clinical research. The research topics available to trainees reflect the multidisciplinary expertise of the participating Mentors and include: pathogenesis of hemorrhagic and thrombotic disorders; regulation of blood coagulation and fibrinolysis; gene therapy of hemophilia and lysosomal storage diseases; phosphoinosi-tide metabolism and cell signaling pathways; mechanisms of hematopoiesis; telomerase defects in bone marrow failure syndromes; molecular basis for protein trafficking in mammalian cells; role of platelets and angiogenesis in metastasis; biology of human immunodeficiency and leukemia viruses; epithelial morphogenesis; pathogene-sis of leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, and congenital neutropenia; cell cycle control; programmed cell death in development and malignancy. Completion of this program will prepare talented trainees for careers in basic and translational hematology research, to make discoveries that will transform the diagnosis and treatment of hematologic diseases.