PROJECT SUMMARY The mission of The University of Chicago (UChicago) Medical Scientist Training Program (MSTP) is to train the next generation of clinician-scientists for impactful careers in the biomedical sciences. Impact is broadly defined as: providing fundamental insights into disease and relevant biological mechanisms, leading or making substantial contributions to translational efforts to identify better therapies and/or filling leadership roles that will determine how limited resources can best be used to improve human health. Our overall objective is to train outstanding and self-directed clinician scientists who can formulate and answer biologically and medically- important questions. To ensure the greatest impact, our program must reflect the diversity of the U.S. population in both who it trains and who it serves. To accomplish our mission and overall objective, we defined 15 specific and measurable objectives that stress the technical, operational and professional skills that support science identity and self-efficacy and are critical for a successful career as an independent biomedical investigator. Two unique features of the program enable our mission and provide an optimal training environment for the development of clinician-scientists. First, we are our own graduate program, the Interdisciplinary Scientist Training Program (ISTP). The ISTP allows integration of graduate and medical school classes in MS1, development of tailored curricula for each trainee, coordination across training transitions and uniform oversight and expectations during the graduate phase. Second, most trainees pursue a 1-4-3 progression of study rather than the traditional 2-4-2 progression. While trainees may pursue a 2-4-2, the 1-4-3 provides a continuous and in-depth graduate experience where trainees become well-trained scientists who can propose and rigorously test hypotheses. The 1-4-3 also provides a seamless transition between the preclinical and clinical phases which facilitates overall success in medical school. Multiple programmatic features ensure that fundamental scientific and clinical knowledge are interwoven to foster the development of impactful clinician-scientists. The UChicago MSTP enjoys sustained and substantial University financial backing including generous direct investment and support of facilities that cultivate innovative science. We are requesting 25 training slots to supplement University investments to support trainees for six of the typical eight years they spend in the MSTP. This requested investment by the NIH would constitute only 13% of total anticipated cost for our MSTP. We anticipate a program size of approximately 80 trainees and expect, based on our track record, that our trainees will contribute significantly to the U.S. biomedical enterprise.