PROJECT SUMMARY - OVERALL The long-term vision of the Vanderbilt Digestive Diseases Research Center (VDDRC) is to continue to inspire interest in the study of digestive diseases and perform paradigm-shifting science that translates to benefit for the patients and communities we serve. The collaborative VDDRC research base is multidisciplinary (88 faculty in 10 Departments; 58 Full members, 30 Associate members), and highly productive as evidenced by 1) 444 peer- reviewed publications (57% collaborative) including 89 in journals with impact factors >10, and 2) robust funding support which increased from $24.7M to $27M (31% NIDDK) since the last competing renewal. The overarching theme that galvanizes members is the study of microbial and host constituents that impact digestive disease pathobiology within the context of inflammation and the environment, and investigative interests fall into three interactive areas: 1) Gastrointestinal Infections and Injury; 2) Progenitor Cells, Development, Regeneration, and Pre-malignant Lesions; and 3) Obesity, Metabolism, and Nutrition. The VDDRC supports four cutting-edge Cores: 1) Cell Imaging, 2) Flow Cytometry, 3) Translational Analysis, and 4) Mass Spectrometry/Proteomics. These cores are highly utilized and well integrated into the Center and provide members with the latest advances in technology. Based directly on investigator demand, we augmented VDDRC Core offerings by adding, among other services: lightsheet microscopy and cryo-EM; spectral high- throughput flow cytometry; inductively coupled MS; as well as digital histology, multiplex IF/IHC, and state-of- the-art probe development for molecular small animal imaging within a strategically reorganized Translational Analysis Core. The VDDRC has now expanded member access to institutional Core services through an innovative Complementary Awards Program supported by new institutional funds ($125K), and extended the impact of the institutionally-supported ($125K) VDDRC Academy of Investigators by using new NIDDK and Academy funds to launch a Diversity Initiative targeting underrepresented minority researchers. A strong Pilot and Feasibility Program generated a 32:1 return on investment for NIH funds over the last 10 years and 96% of awardees remain active in GI research. The Pilot Program receives institutional support of $100K/year and we have now established new partnerships with Vanderbilt Centers to co-fund additional content-appropriate Projects. A responsive Administrative Core oversees financial management and operations and contains a Biostatistical Component and an Enrichment Program, which sponsors seminars and retreats to promote scientific collaboration and the development of new initiatives. The VDDRC also broadened its impact as 1) member publications involved collaborators at 504 institutions worldwide, and 2) the Center is now engrafted within a newly minted NIDDK-funded Eastern Regional DDRCC Alliance to promote the professional developmen...