PROJECT SUMMARY The mission of the Tri-Institutional MD-PhD Program (Tri-I) is to train a diverse and empowered group of clinician-scientists prepared to bridge the gap between laboratory research and clinical medicine. Graduates of the program are well-grounded in human biology, pathophysiology, and clinical medicine and are endowed with an advanced understanding of biomedical science, as well as a mastery of critical thinking and experimental skills. These skills will allow them to undertake complex, interdisciplinary, quantitative, and collaborative studies to elucidate basic biological processes pertaining to human health and disease and to transfer advances in research to the understanding, prevention, and treatment of human disease. Tri-I is a joint undertaking between Weill Cornell Medicine (WCM), The Rockefeller University (RU), and Memorial Sloan Kettering Cancer Center (MSK). Trainees complete their MD degree at Weill Cornell Medical College (WCMC), and PhD training at one of the three participating graduate schools: Weill Cornell Graduate School of Medical Sciences (WCGS); the David Rockefeller Graduate Program in Bioscience at RU; or the Louis V. Gerstner Jr. Graduate School of Biomedical Sciences (GSK) at MSK. An integrated curriculum reinforces the students’ identities as clinician- scientists. In the first two years in the program, MD-PhD-specific graduate-level coursework, including training in quantitative methods, responsible conduct of research, and rigor and reproducibility, is integrated with pre- clinical medical school courses and 18 weeks of core clinical clerkships. Students complete three laboratory research rotations in at least two different institutions before selecting a thesis lab and enrolling in the graduate school at which their thesis mentor has their primary appointment. PhD requirements are comparable for all MD- PhD students across graduate institutions, and trainees may take courses for credit in any of the graduate schools. After they have defended their thesis, trainees complete their remaining clinical training at WCMC. Over 200 participating faculty members serve as mentors and undergo training to ensure a safe training environment, responsible conduct of research, and scientific rigor and reproducibility. Students receive multi-layered mentorship and advising, particularly around transitions to and from the laboratory and in preparation for post- graduate residency training. Based on Tri-I’s high trainee retention in the program and in academia and biomedical research following graduation, this application requests funds to support 49 trainees per year. No trainee will be appointed to the grant for more than a total of four years. The student body averages 150 MD- PhD trainees; currently, 47% identify as women and 23% come from racial and ethnic backgrounds underrepresented in medicine and science. Over the past 50 years, 451 MD-PhDs have graduated from Tri-I and its predecessors. In the past 15 years, ...