Diabetes affects some 30 million people in the US. Both Type 1 and Type 2 diabetes ultimately result from failure of beta cell mass and/or function. Human islets and beta cells are similar to their rodent counterparts in many ways, but also differ in important ways. Accordingly, the NIDDK, ADA and JDRF are increasing their focus on research in human beta cell and islet biology. Indeed, research focused on human islets is essential for translating important insights from rodent islets and beta cells into significant advances in human diabetes research and treatment. The Human Islet and Adenovirus Core (HIAC), located at Mount Sinai, was created five years ago to support the research base of the Einstein-Sinai Diabetes Research Center (ES-DRC), as well as regional investigators pursuing islet biology, by providing special emphasis on human islets. During the previous funding cycle, the HIAC provided expertise and services to 50 investigators supporting 41 publications and 22 federally and non-federally funded grants. Consequently, we propose to expand these sought-after services and to further enhance access and availability of islet-relevant education, services and technology to diabetes researchers in the New York City region. The first mission is to provide key advice, methods, technology and infrastructure to assist investigators in the use of human islets for research, with the goal of furthering understanding of normal and pathophysiologic islet cell growth and function. The second mission is to generate, and make available to the ES-DRC community, reagents and tools including adenovirus or lentivirus viral vectors for gene delivery of cDNAs and shRNAs of interest beta cells and other islet cell types to study beta cell regeneration, differentiation, survival and function. These missions will be achieved by developing the following Specific Aims: 1) To assist new islet investigators in obtaining in accessing human and rodent islets and related cell lines for use in investigator-driven studies; 2) To train students, postdoctoral fellows, investigators and technical staff in the design and use of molecular, cellular and physiologic approaches to human and rodent islet biology and pathophysiology; 3) To provide pure populations of live human beta cells using fluorescence- activated cell sorting (FACS) and/or to facilitate the use of specialized protocols, adenovirus/lentivirus and transduction methods for gene delivery to rodent and human beta cells and islets that enhance investigator- initiated research; 4) To conduct specialized assays for the determination of insulin secretion, islet bioenergetics and beta cell differentiation, proliferation, survival and mass in vitro and in vivo using syngeneic, allotransplant or xenotransplant of rodent/human islets into immunocompromised euglycemic or diabetic mouse models; and 5) To assist investigators with study design and data interpretation to advance experimental approaches focused on the molecular and physiologic basis of human islet cell function and dysfunction in Types 1 and 2 diabetes.
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