The ubiquitous distribution and actions of gut peptides on GI health and diseases catalyzed the formation of the University of Michigan Gastrointestinal Peptide Research Center, which has been funded as a NIDDK P30 Research Core Center since 1984. These peptides now extend beyond their classical role as hormones to include actions as paracrine effectors, neurotransmitters, growth factors and cytokines. Hence we changed the name of our Center to the University of Michigan Center for Gastrointestinal Research to more accurately reflect the comprehensive mission. The overreaching goal is to investigate signal transduction mechanisms regulating homeostasis and GI disorders. Our approach will include studies on genetics and gene regulation, cellular signaling pathways, receptors and ion channels. Our Research Base consists of 58 scientists and clinical investigators with over $26 million in GI-related funding. The goals are to: (a) enhance rapid translation of basic discoveries into clinical applications by providing a facilitative infrastructure to stimulate interactions between basic scientists and clinical investigators; (b) promote interdisciplinary collaborative projects to broaden the base of research that crosses traditional scientific boundaries; (c) offer specialized technologies, equipment, reagents and expertise to assist Center members; (d) identify and nurture new GI investigators via peer-reviewed pilot and feasibility program and career development workshops; (e) develop scientific enrichment including visiting faculty programs, cross-disciplinary special topic seminars, new technologies workshops and an annual Retreat where Center and guest Investigators may present their work. The 3 major research themes reflecting the common research interests of numerous investigators affiliated with the Center remain unchanged: 1) Neurobiology of visceral pain, enteric motility and appetite control, 2) Molecular and Cellular Mechanisms of Inflammation, and 3) Cell Growth Differentiation and Programmed Cell Death. In response to advances in new technologies and membership needs, we organized our Core labs into (I) Molecular biology; (II) Protein localization, identification and folding; (III) Microbiome and metabolomics, and (IV) In vivo animal and human studies. New changes include expanding Core I to include whole genome sequencing and bioinformatics analysis, and genome-editing technology for molecular and animal studies. Expanding Core II to include the characterization of protein folding and specialized proteomics, to facilitate studies on protein misfolding that are important in the pathogenesis of pancreatitis, fatty liver and IBD. Core III aimed at host-microbiome interactions and added a metabolomics arm to examine the functional pathways regulating such interactions, and to study metabolome contributions to GI disease. Core IV expanded to include an organoid service, biospecimen banking service and clinical design and statistics program to accelerate the translation of basic science findings to clinical application. Through these enhancements we seek to solve fundamentally important questions in the pathophysiology, diagnosis and treatment of GI disease.