PROJECT SUMMARY The mission of our multi-institutional MD/PhD Program, comprised of the University of Texas Health Science Center at Houston McGovern Medical School (UTHealth) and MD Anderson Cancer Center (MDACC), and in conjunction with the University of Puerto Rico Medical Sciences Campus School of Medicine (UPR), is to pursue novel training of a diverse group of intellectually gifted students for careers as physician-scientists focused on disease-oriented research and bridging the knowledge gap between medicine and basic science. The MD/PhD program has been continuously funded since 1982 and has graduated 105 students, including a current Director of our program. To expand diversity in our physician-scientist trainees, we have partnered with the UPR, leveraging a NIH-funded MDACC/UPR U54 Partnership for Excellence in Cancer Research award to integrate into our MD/PhD Program those talented UPR medical students who want to pursue research careers, and approximately 30% of our program is underrepresented minorities (URM). Applications to our program from students from across the country have doubled over the past 10 years, allowing us to matriculate a group of highly qualified students (51 students currently in the program). To prepare physician-scientists to pursue disease-oriented research, a novel educational sequence was established to integrate the medical and graduate school. Although students begin to fulfill graduate school requirements from the very beginning of the program, they complete the clinical specialty rotations before pursuing dissertation research. Students can select from 9 graduate training programs in biomedical sciences. Support for this educational sequence is provided by the fact that, in the past 10 years, attrition from the program has been 4% and the time to completion is 7.8 years. The quality of students and the program are exemplified by strong publication records and excellent residency matches. A major element to enhance training is the Topics in Molecular Medicine course, which provides vertical integration and community for the students, exposure to the breadth and depth of research at the institutions, and insights into career development and leadership. Based on graduates over the past 15 years, the majority of our post-training trainees are in academic positions or industry (76%; n = 38; 28 academic positions + 1 in industry). MSTP support is requested for a total of 6 matriculating students per year by year 3 of the training grant period, to expand the number of students in this unique and diverse training program.