Project Summary The purpose of this program is to provide rigorous multidisciplinary research training for physician-scientists and PhD postdoctoral fellows in cardiovascular research. Our training program incorporates two guiding principles: 1) biomedical research requires teams of investigators with diverse scientific backgrounds and complementary expertise, and 2) there are no shortcuts to a career in cardiovascular research; rigorous didactic training, structured mentorship, a focused research project, and constructive feedback are required. The program is centered in the University of Pennsylvania Cardiovascular Institute (CVI), which includes 115 members across multiple university departments performing a broad spectrum of cardiovascular science. Considerable support from the School of Medicine is committed to the program, including integrated basic and translational research space and core laboratories in the Smilow Center for Translational Research. This renewal application will support 7 MD, MD/PhD, and PhD postdoctoral fellows per year performing 2-3 years of dedicated research training. Thirty-eight NIH-funded Penn CVI faculty in the Departments of Medicine, Surgery, Cell and Developmental Biology, Genetics, Physiology, Systems Pharmacology and Therapeutics, and Bioengineering serve as trainers and mentors. Three tracks have been created. The Basic Track prepares trainees for careers in cardiovascular science using laboratory approaches. The Clinical/Translational Track prepares trainees for research careers at the interface of laboratory science and clinical investigation, including deep-phenotyping in human subjects, applied genomics, novel devices, and therapeutics. The Outcomes/Health Services Research Track prepares trainees for careers that leverage big data to improve health care delivery. The core of our curriculum is a supervised research preceptorship. Training is supplemented with didactic classwork, lectures, seminars, skills classes, and Master’s level research training. Over the past 15 years metrics of the program’s success include: 1) recruitment of outstanding MD, MD/PhD and PhD trainees, 2) > 95% of trainees completing the program (several having obtained advanced degrees), 3) an average of 4.3 manuscripts published per trainee (many in high-impact journals), 4) a vast majority of trainees moving on to research careers or additional postdoctoral studies. Programmatic enhancements include new leadership and discovery units in the Penn CVI; new translational programs in the Cardiovascular Division; an expanded roster of Program Directors, Co-Directors, and Faculty Trainers, including women, URM and early career trainers; a renewed external advisory committee; new themes, including bioinformatics, data science, social determinants of disease, and the impact of COVID-19; and new structures to promote cross- disciplinary interaction, team science, and peer mentoring. Finally, we have substantially updated our plans to recr...