PROJECT SUMMARY Gout impacts around 4% of the U.S. adult population and is the most common form of inflammatory arthritis in men. The incidence of gout is increasing worldwide and may be as high as 9% in the elderly. Gout is a significant burden on the healthcare system, and is associated with both decreased work productivity and quality of life. With the ever-increasing impact of gout and its associated comorbidities on the population, investigation of novel translational mechanisms mediating gout flares as well as approaches to improving gout and hyperuricemia outcomes comprise an unmet and urgent medical need. Our multi-disciplinary INvestigationS In Gout, Hyperuricemia, and comorbidiTies (INSIGHT) Center of Research Translation (CORT) includes 4 research projects and an Administrative Core focused on the theme, ?Gout, Hyperuricemia, and Associated Comorbidities?. CORT projects will include studies to: determine if innovative peripheral blood leukocyte adenosine monophosphate-activated protein kinase (AMPK) activity metabolomics have promise as gout flare biomarkers independent of serum urate (Project 1), examine the influence of key gene-environment interactions within an internet case-crossover study of gout flares (Project 2), unravel the functional genomics of urate transporters genes identified in previously reported genome wide association studies (Project 3), and investigate the mechanism of urate lowering therapy on renal function within the soon to begin comparative study of gout therapies (VA STOP-GOUT) (Project 4). Projects range from basic research translation of underlying genetics and relevant inflammatory pathobiology of gout, to understanding mechanisms of CKD progression in gout, and translation of genetic interaction with environmental factors and medications to precision medicine. Our INSIGHT CORT aims to: (1) Conduct four outstanding, innovative, and synergistic translational research projects drawing on the unique strengths of multidisciplinary research teams at our three major centers: University of Alabama at Birmingham, Harvard University, and University of California San Diego. (2) Foster the development of pilot and feasibility projects and the development and application of new translational methods to research in gout and hyperuricemia and their associated major comorbidities, particularly chronic kidney disease and metabolic syndrome. (3) Promote training of translational investigators in current methods of research applicable to gout and hyperuricemia through enrichment activities overseen by our Administrative Core. The INSIGHT CORT reflects a focused, relevant, multi-disciplinary translational research program at UAB and partner institutions. The INSIGHT CORT has assembled an outstanding scientific team and is uniquely prepared and strongly committed to scientific rigor, innovation, and development of new knowledge and translational techniques clinically relevant to the mission NIAMS.