PROJECT SUMMARY The GI training program of the Massachusetts General Hospital (MGH) remains dedicated to the preparation of investigators committed to a career in GI biomedical research. This program continues to build on its extensive past experience in training productive and committed digestive diseases investigators (>95% of trainees in past 10 years remain in academic GI). Fundamental features of the post-doctoral training format, the major component of this program, include direct research participation in conjunction with a comprehensive program of didactic instruction and enrichment activities to provide a deep foundation in biomedical science and modern research techniques. In addition, continuation of a 1-2 year pre-doctoral laboratory research program is proposed to attract promising candidates to careers in GI research at a critical juncture in their careers. The strength of the research base of this program encompasses a spectrum of research interests. The majority of trainees will undertake training in laboratory research in which emphasis is placed on the application of tools of molecular biology to GI research. Training is offered in several disciplines central to the study of digestive diseases: Epithelial Biology, Developmental Biology, Immunology, Metabolism, Host-Pathogen Interactions, Genetics, Cancer Biology, Stem Cell Biology, Systems Biology, the Microbiome, and Tissue Engineering. For fellows undertaking training in clinical investigation, a rigorous preparation in relevant quantitative sciences, including Biostatistics and Epidemiology, Biomedical Informatics and Population Health, is provided. In all disciplines, updated formal work in the Responsible Conduct of Research is offered. This renewal proposes both post-doctoral and pre-doctoral training. Post-doctoral training is offered to individuals holding M.D., M.D.-Ph.D. or relevant Ph.D. degrees. Seven post-doctoral positions are requested: four post-doctoral fellows will begin training each year and remain in research training for a minimum of two years supported by this award. In addition, two positions are requested to continue the pre-doctoral training fellowship for promising candidates completing an undergraduate degree or enrolled in graduate or medical school, each student entering for a 1-2 year period. Research training will take place in the existing laboratories of the research mentors; a group of 54 established investigators with extensive ongoing interactions. Laboratories are present at the MGH, a large general hospital with more than 1,300,000 sq. ft. of space dedicated to research. In addition, training opportunities will be available in laboratories elsewhere at M.I.T., the Whitehead Institute, Harvard Medical School, the Ragon Institute, and the Broad Institute. Didactic educational programs will include those offered through the Harvard Medical School, other affiliates of the Harvard Medical School, the Harvard School of Public Health, Harvard Univ...