PROJECT SUMMARY – OVERALL This is a renewal application for support of the Yale University Digestive Disease Research Core Center, a multidisciplinary Center whose research focus is Liver Structure, Function and Disease. Thirty-four independently funded investigators comprise a current digestive disease related-research base of ~$23 million, and all of these individuals actively collaborate with other Liver Center members. There are an additional 52 associate members engaged in liver-related research, 40% of whom also have independent funding. Research programs in the Center are distributed across 17 Departments of the University including Biomedical Engineering; Cell Biology; Cellular and Molecular Physiology; Comparative Medicine; Epidemiology and Public Health; Human Genetics; Immunobiology; Internal Medicine; Microbial Pathogenesis; Molecular Biophysics and Biochemistry; Obstetrics and Gynecology; Pathology; Pediatrics; Pharmacology; Radiology, Surgery, and Urology. The research base focuses on three major basic/translational themes: (1) Hepatic metabolism, (2) Immunobiology and inflammation, and (3) Epithelial biology/pathobiology. The research programs are broad and range from fundamental studies of the biology of liver and related digestive systems to translational studies of immediate clinical relevance. The major areas of liver disease examined within these translational themes include autoimmune diseases, cholestasis, fibrosis/cirrhosis, genetic diseases, infections, liver cancer, and NASH/ASH. The major goals of the Center continue to be: (1) to stimulate multidisciplinary interactions between basic and clinical faculty and departments, (2) to provide an in-depth training environment, (3) to efficiently organize time consuming, often costly techniques and procedures in Core Facilities for use by multiple investigators, (4) to stimulate basic scientists to direct their focus to areas of interest to the Center, (5) to stimulate translational research from bench to bedside, (6) to promote new research and training opportunities with a pilot feasibility program, and (7) to create an intellectual environment within the field by fostering collaborations both within and outside the institution through its enrichment program. To achieve these goals the Center is organized into four Core Facilities including: (1) Administrative Core, (2) Cellular and Molecular Physiology Core, (3) Morphology Core and (4) Clinical/Translational Core. A Pilot Feasibility Program supports one- to two-year small grants for new scientific initiatives. The Enrichment Program consists of research seminars, symposia, visiting professorships, and retreats.