PROJECT SUMMARY The overall goal of our Digestive Health Center (DHC): Bench-to-Bedside Research in Pediatric Digestive Disease is to promote research that will yield insights into the fundamental processes and pathogenic mechanisms of digestive disease in children and generate innovative treatment to restore digestive health. The Cores aims are: 1) to strengthen the Research Base and foster collaborations, 2) to catalyze discoveries by giving investigators access to highly innovative Cores, and 3) to develop junior investigators and the future leaders in the field. The last award period of the DHC was very successful, with Core services that evolved to meet the scientific needs of innovative investigators. Our Research Base of 68 investigators attracts $36.5 million of extramural digestive disease-related funds annually; they published 630 articles in the last 4 years. Several Pilot and Feasibility (P/F) Awardees transitioned to R01-funded investigators and the entire research community benefitted from a scientific Enrichment Program presenting the latest advances in digestive disease research. This trajectory of success will be pursued in future years by fostering research and promoting interdivisional and interdepartmental collaboration to maintain a solid critical mass in digestive disease research with a focus on translational research. Specifically, our long-term goals are to improve child health through better diagnosis, treatments and outcomes that will emerge from highly innovative work in our three key focus areas: 1) Mechanisms of Liver Disease modeling, 2) Digestive Disease and Immunity, and 3) Stem Cell and Organoid Modeling of Digestive Diseases. Each focus area brings opportunities for potential impact on the digestive health of children, helps advance the national research agenda, and creates a unique environment to integrate research into patient care. The focus areas are linked by three complementary and uniquely innovative Biomedical Research Cores (Gene Analysis Core, Integrative Morphology Core, and Stem Cell/Organoid Core and Genome Editing Core) and by a Clinical Component of the Administrative Core to facilitate patient-based research. Collectively the Cores and the Clinical Component form a powerful infrastructure that fosters the development of personalized and predictive medical approaches based on the genetics and molecular basis of GI disorders, and of therapies that take into account basic mechanisms of disease. Our working model promotes laboratory discoveries to generate translational research opportunities that lead to validation in patient samples and lead to clinical trials. To strengthen digestive disease research, the DHC will foster collaborations among its investigators and investigators from other disciplines. It will also fund highly promising P/F Projects for junior investigators and will sponsor a dynamic Enrichment Program of scientific seminars, workshops and symposia. With these strategies and an exc...