PROJECT SUMMARY (OVERALL) The Center for Molecular Studies in Digestive and Liver Diseases (abbreviated as CMSDLD) is a NIH/NIDDK Digestive Diseases Research Core Center (DDRCC) where it has served as the nidus for the expansion of digestive and liver disease research at the University of Pennsylvania for the past 25 years and successfully promoted interdisciplinary interactions spanning multiple departments, institutes, and schools at the University. The CMSDLD has witnessed robust and vibrant growth in scientific research, collaborations and interactions between members, maturation of the initial young investigator base and incorporation of new associate members, vigorous use and evolution of state-of-the-art scientific core facilities, cohesion-fostering enrichment activities, and a highly successful pilot and feasibility grant program. This has led to a marked increase in institutional support from the leadership of Penn Medicine and The Children’s Hospital of Philadelphia (CHOP), with growing collaborative interactions with the Philadelphia VA Medical Center (aka Corporal Michael J. Crescenz VA Medical Center) uniquely positioning the CMSDLD for success in the current decade and beyond. The impact that the environmental factors such as diet and the gut microbiota play in health and disease, particularly related to the GI tract and liver, is enormous but incompletely understood especially in humans. At UPenn, there is now an unprecedented opportunity to leverage resources, technologies and collaborative multidisciplinary expertise to address gaps in knowledge and unmet needs relating to these issues. The membership of the research base has gradually evolved to investigations relevant to the new theme of the Center: Host-environmental interactions in digestive and liver disease research from bench to bedside. The research base of the Center now consists of 45 full and 14 associate members streamlined into three research themes, (1) Intestinal Biology; (2) Liver Biology; and (3) The Microbiome, supported by four biomedical research cores: Genetically Modified Mouse Core, Molecular Pathology and Imaging Core, Host-Microbial Analytic and Repository Core, and the Biomedical Data Science Core (Clinical Core). The membership maintains a strong base of digestive and liver disease research funding of $35.3 million dollars annual directs (32.3% NIDDK) representing a significant increase in total DDN research funding, an increase in %NIDDK funding, and greater cohesion. Greater emphasis on translational and human subject research and, with the addition of a new core on ‘big data’ analytics, provides enhanced opportunities for collaborations focused on host-environmental interactions. Finally, the Center continues to develop the future of research in digestive and liver diseases by actively supporting trainees and junior faculty with enrichment activities and by attracting new researchers through our Pilot and Feasibility Award program that has resulted in significant R01 funding for our awardees.

PROJECT NARRATIVE (OVERALL) The Center for Molecular Studies in Digestive and Liver Diseases (CMSDLD) supports a diverse community of basic, translational, and human subject researchers focused on digestive and liver disease at the University of Pennsylvania Perelman School of Medicine, the Children’s Hospital of Philadelphia and the Corporal Michael J. Crescenz VA Medical Center. Through its four biomedical research core facilities overseen by an administrative core, CMSDLD fosters multidisciplinary collaborative research amongst the Center’s membership focused on the prevention and treatment of disease. Promotion of advances in research knowledge is enabled by a robust enrichment series with financial support for the development of junior investigators made possible through a Pilot and Feasibility grant program.