STANFORD ISLET RESEARCH CORE (SIRC): PROJECT SUMMARY/ABSTRACT The specialized expertise of the SDRC Islet Research Core (SIRC) provides SDRC investigators with the capacity to perform modern molecular, cellular and functional studies of high-quality islets and pancreata from rodents and humans. The SDRC’s large group of collaborative investigators study a broad spectrum of islet biology in physiological or pathological settings, including islet development, functional maturation, maintenance of mature cell fate, proliferation, genetics, epigenetics, gene regulation, inter-organ signaling, intra-islet cell signal transduction, islet immunology, and aging. A central aspect of the SIRC is our direct focus on parallel studies in rodent and human tissues. An essential component supporting the majority of studies falling under this paradigm is our ability to isolate high-quality, well characterized rodent or human primary pancreatic islets, and then to perform assays of islet cellular, molecular and physiological phenotypes. This is coupled with a reliable, robust program to procure high-quality human islets that have increased the number of SDRC investigators studying human islet biology. The support of transplantation-based studies of human islet cell function, growth and fate by the SIRC also enhances potential translational studies of human islets for diabetes. In addition to these services, the SIRC is committed to training investigators in specialized methods of islet biology, like islet isolation and transplantation, islet culture and specialized assays including insulin or glucagon ELISA, islet perifusion and static batch insulin secretion assays, and immunohistology. SIRC personnel work closely with SDRC investigators to build efficient experimental strategies tailored to their aims. These islet-focused services or activities would be lost without P30 support of this unique Stanford research core. The SIRC also serves the Stanford community and the SDRC by continuously developing new experimental capacity to match the dynamic demands of modern islet investigations. This includes assays of islet function, new approaches to investigate human islet cell genetics, new models of islet transplantation, and assistance in developing new clinical islet programs at Stanford Health Care, like the Stanford Pancreatic Islet Replacement and Immune Tolerance (SPIRIT) clinical islet transplantation programs. The SIRC also enhances the use of other SDRC Research Cores by integrating activities with those cores. Together with the Diabetes Immune Monitoring Core (DIMC) and the Diabetes Genomics & Analysis Core (DGAC), the SIRC collaborates on efforts permitting cellular, genetic, molecular, physiological and genome studies of human pancreas- and immune or blood cells, including immune, stromal and vascular cells. The SIRC will also serve SDRC members at University of California (UC) Berkeley or at UC Davis, including those supported through the proposed Regional Pilot & Feasibility Award expansion. Based on growth of the SDRC membership, evolution of exciting new services, increasing membership demand for human islets, and the increased research focused on islet biology in the SDRC, we anticipate growth of demand for SIRC services in the coming years.