CENTER OVERALL: PROJECT SUMMARY This COBRE proposal seeks to establish the Kansas Center for Metabolism and Obesity REsearch (KC-MORE) which will unify investigators from multiple departments and research centers at the University of Kansas Medical Center to focus research on the pathology of obesity, metabolic dysfunction, and obesity-related disease. Obesity is a critical problem that is harming the health of people in Kansas as well as the entire U.S. New research-driven solutions and therapies are needed to prevent and treat obesity, investigate metabolic signatures that underly obesity, and examine mechanisms by which obesity initiates chronic disease. The KC- MORE will serve to merge these areas of focus by (1) creating a shared intellectual home for obesity-related researchers through a common educational and seminar program, (2) providing funding and mentorship for early stage obesity-related investigators to establish independent research careers, (3) establishing scientific cores to facilitate translational research of both early stage and established investigators, and (4) partnering with departments to jointly recruit new investigators to KUMC focused on themes of the KC-MORE. This central role in leading and coordinating obesity research and incentivizing future resources and recruitment will allow KUMC to synergize efforts and form multi-disciplinary collaborations on obesity, metabolism, and obesity-induced disease research in ways that would not occur without COBRE funding. The KC-MORE will be led by two multi- PIs, Drs. Steven Weinman and John Thyfault, and a renowned senior investigator, Dr. Joseph Donnelly who will serve as Chair of the Steering Committee and lead human energy balance research. These leaders have multi- disciplinary but complimentary expertise in basic, clinical, and translational research. Phase 1 of the Center will support the development of four Research Project Leaders (RPLs) with studies on neural control of energy balance, clinical-based approaches to weight loss in rural communities, and basic mechanisms of obesity-related fatty liver disease and hypertension. KC-MORE will also administer a Pilot Awards Program to develop additional KC-MORE researchers. The KC-MORE will lead 3 new scientific cores that provide a foundation for translational research capabilities (the Metabolism (MET) core, the Cells, Tissues, Bioanalysis and Bioinformatics (CTBB) core, and the Human Energy Balance (HEB) core). The cores will support infrastructure and methodologies for the Research Project Leaders, the Pilot Award recipients, and a large pool of established obesity-related researchers on campus. A critical goal of phase 1 of the KC-MORE COBRE will be to help RPLs develop independent, R01-funded research programs. Overall, the establishment of the KC-MORE will serve to develop a translational and multi-disciplinary obesity research program that will have a significant future impact by reducing the burden of obesity-related disease conditions.

CENTER OVERALL: PROJECT NARRATIVE This application seeks to establish the Kansas Center for Metabolism and Obesity Research at the University of Kansas Medical Center. This center will coordinate the activities of existing investigators, develop three new research cores, and mentor the career development of new investigators. It will create the intellectual and physical infrastructure necessary to develop new treatments for obesity, metabolic dysfunction, and obesity related complications.