PROJECT SUMMARY - OVERALL This application is for continued support of the Vanderbilt Digestive Disease Research Center (VDDRC). Our long-term objective is to develop a deeper understanding of gastrointestinal pathophysiology in order to reveal new disease mechanisms and identify novel therapeutic targets. Our vision 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 VDDRC is multidisciplinary, including faculty in 14 different academic departments with 84 investigators (54 full members and 30 associate members). The Aims of the VDDRC are to: 1) promote digestive diseases research in an integrative, collaborative, and multidisciplinary manner; 2) attract new investigators to the study of these disorders; 3) enhance the innovative research capabilities of members; and 4) promote the career development of junior investigators. The overarching VDDRC theme is the study of microbial and host constituents that impact digestive disease pathobiology within the context of inflammation and the environment and investigative member interests fall into three interactive areas of study: 1) Gastrointestinal Infections and Injury; 2) Progenitor Cells, Development, Regeneration, and Pre-malignant Lesions; and 3) Obesity, Metabolism, and Nutrition. The VDDRC contains four core research laboratories to support members: 1) Flow Cytometry Core, 2) Preclinical Models of Digestive Diseases Core, 3) Cell Imaging Core, and 4) Mass Spectrometry/Proteomics Core. These cores are well engrafted into our Center to provide investigators working on digestive disease-related research with the latest advances in technology, to actively promote collaborations, and to aid in experimental design and interpretation of results. Based directly on investigator demand, we have now expanded our core services by adding organoid development to the Preclinical Models of Digestive Diseases Core, and created the VDDRC Academy of Investigators as a Component of the Enrichment Program to provide career development and support to junior investigators. The VDDRC supports a Pilot/Feasibility Program including a university-supported translational project, a dual- funded VDDRC-Clinical and Translational Science Award clinical project, and a Young Investigator Award Program to foster participation of beginning and seasoned investigators in research related to digestive diseases. The Administrative Core also contains Biostatistical and Enrichment Programs and oversees the financial management and operation of the VDDRC.