CLEVELAND DDRCC OVERALL PROJECT SUMMARY This competitive renewal application is to obtain continued funding for the Cleveland Digestive Diseases Research Core Center (DDRCC), which is a combined effort between Case Western Reserve University (CWRU) and the Cleveland Clinic Foundation (CCF). The Cleveland DDRCC's mission is to: 1) enhance the research capabilities of Center investigators, 2) develop and implement programs to support the independent development of young investigators, 3) attract established investigators not currently involved in digestive disease research to apply their expertise to this important area of investigation, and 4) facilitate the translation of basic research discoveries to the clinical arena. This cross-institutional and multi-disciplinary Center currently includes 47 full members and 35 associate members from 25 different academic departments across CWRU and the CCF, representing a steady expansion during the previous funding cycle. Together, these investigators comprise the Research Base for the Center, which currently consists of $17.3 million in peer- reviewed federal and foundation grants (52 NIH, 5 DOD/VA, 10 private foundation grants) specifically related to the two scientific themes of the Cleveland DDRCC: Digestive Inflammation/Tumorigenesis and Liver Disease/Metabolism. These two programmatic areas have strong historical track records of collaborative investigation at CWRU and the CCF and have shown significant growth in collaboration during the previous funding cycle. The Center enjoys strong institutional support, including a commitment of significant matching funds from both CWRU and the CCF to increase the impact of digestive disease research at both institutions. The Center includes three biomedical research cores to support this strong Research Base: 1) a Biorepository Core, 2) an Histology/Imaging Core, and 3) a Mouse Models Core, all of which have demonstrated high levels of usage by Center members and promoted important scientific discoveries in digestive diseases during the previous funding cycle. Each Core includes both a set of high-volume standard services that are best provided as a shared resource that can optimize cost-efficiency and quality control, as well as more cutting-edge advanced services and technologies that may not otherwise be available to Center investigators. The Core laboratories interface with a Administrative Core, which also supports a successful Pilot and Feasibility Program to promote innovative research projects by investigators who are new to the area of digestive diseases. The Administrative Core oversees the financial management and operation of the Cleveland DDRCC and supports a Clinical Element, as well as a dynamic Enrichment Program that has supported the meetings of the Midwest DDRCC Research Alliance and two Cleveland International Digestive Education and Science (IDEAS) Symposia during the previous funding cycle. The overall objective of the Cleveland DDRCC is to increase the availability of Core resources for Center members, and to foster research, collaborations, and new directions in digestive disease research, leading to important scientific discoveries.

OVERALL PROJECT NARRATIVE The Cleveland Digestive Diseases Research Core Center (DDRCC) is focused on pathogenic mechanisms of Digestive Inflammation/Tumorigenesis (i.e., inflammatory bowel disease, colon cancer, Barrett’s esophagus, etc.) and Liver Disease/Metabolism (i.e., hepatitis, metabolic syndromes, obesity, etc.), which affect millions of people in the US. By providing state-of-the-art services to DDRCC investigators at two major Cleveland institutions (Case Western Reserve University and the Cleveland Clinic Foundation), the Center fosters multi- disciplinary collaborative research, leading to new discoveries and treatments, thus having a large impact on the health of patients suffering from digestive diseases.