The MD-PhD Program at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences is designed to train physician-scientists. Our goal is to provide an outstanding cadre of investigators well-versed in both the conduct of basic and translational research and in the practice of medicine. We achieve this goal by providing an integrated approach to training, including a newly revised medical curriculum with the flexibility that dual degree students require. Medical training interfaces with eight basic science PhD programs in Biochemistry, Cellular & Molecular Physiology, Cell, Molecular & Developmental Biology, Genetics, Immunology, Molecular Microbiology, Neuroscience, and Pharmacology & Experimental Therapeutics. We have transformed our program during the past six years. We have enhanced trainee advising, and created a new set of MD-PhD Program courses and workshops that provide strong student support and improved program integration. Our new June matriculation date and the ability for our students to explore research during their pre-clinical years of medical school enhance integration and decrease time to degree. Our new medical curriculum allows students to complete a required clerkship prior to entering graduate school in a manner that does not delay the start of research training. A second required four-week clerkship is completed during graduate training, which allows students to stay firmly connected to clinical medicine and also facilitates flexibility in re-entryto medical training when the PhD is complete. In addition to our Clinical Implications of Basic Research course, an annual retreat and our career-oriented dinner program, we have added a series of skill-building workshops. These include preparation for the transition from graduate school to clinical medical training, mentoring for NIH application, a women physician-scientist group and a workshop focused on choosing research-focused residencies. With a strong institutional commitment to the Program, we have expanded our enrollment through a Second Portal program for trainees already enrolled in medical school and increased the size of the incoming first year class to five trainees each year. Our Program has graduated 68 trainees since its inception and 33 are currently enrolled. Five additional trainees are slated to matriculate this June. We are requesting funding for 12 positions in this application.