Diabetes is a substantial public health problem in the United States. Decreased or dysfunctional pancreatic beta cell mass underlies most types of diabetes. Securin (also called """"""""PTTG"""""""") regulates chromosome separation during cell division. Deletion of the securin gene from mice results in decreased beta cell mass and diabetes in male animals. In this grant proposal, I aim to study the mechanism for securin regulation of beta cell mass.
The specific aims are to experimentally test the following hypotheses: 1) Securin deletion causes intrinsic defects in beta cell replication; 2) Defective regulation of chromosome separation causes beta cell-specific abnormal cell cycle progression and inhibits beta cell replication; and 3) beta cell neogenesis is intact in securin-null mice. The knowledge gained from these studies will help elucidate mechanisms for diabetes pathogenesis. I am currently a fellow in the Division of Endocrinology, Cedars-Sinai Medical Center, UCLA and will complete my fellowship in June 2005. Through the studies, I will expand my knowledge of diabetes pathogenesis and beta cell biology. By the end of this grant period, I will be ready to undertake independent research in diabetes pathogenesis and to pursue a productive research career in academic medicine. Cedars-Sinai Medical Center has excellent active basic research and a tradtion of nurturing physicians to develop independent careers in academic medicine. CSMC has well-established programs related to my proposal and research interests and is fully committed to sustain my research career development in an environment of academic excellence. I will be mentored by the endocrine faculty including my mentor, Shlomo Melmed, and an oversight committee (Drs. John Adams and Basil Rapoport). Building on my extensive basic and clinical training, I expect to become an independent endocrine researcher upon completion of this K08 grant .

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Clinical Investigator Award (CIA) (K08)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Hyde, James F
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Cedars-Sinai Medical Center
Los Angeles
United States
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Yu, Run; Chen, Chun-Rong; Liu, Xiaohong et al. (2012) Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones. J Mol Endocrinol 49:69-78
Yu, Run; Ren, Song-Guang; Mirocha, James (2012) Glucagon receptor is required for long-term survival: a natural history study of the Mahvash disease in a murine model. Endocrinol Nutr 59:523-30
Yu, Run; Wawrowsky, Kolja; Zhou, Cuiqi (2011) A natural inactivating mutant of human glucagon receptor exhibits multiple abnormalities in processing and signaling. Endocrinol Nutr 58:258-66
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Zhou, Cuiqi; Dhall, Deepti; Nissen, Nicholas N et al. (2009) Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas 38:941-6
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