SECURIN REGULATION OF PANCREATIC beta CELL MASS

SECURIN 对胰腺 β 细胞质量的调节

• 批准号: 7234120
• 负责人: Run Yu
• 金额: $ 12.63万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234120
• 关键词: Abnormal Cell; Address; Animals; Applications Grants; Basic Science; Beta Cell; Cell Cycle; Cell Cycle Progression; Cell Proliferation; Cell division; Cells; Cellular biology; Chromosomes; Clinical; Commit; Crossbreeding; Defect; Development; Diabetes Mellitus; Dominant-Negative Mutation; Endocrine; Endocrinology; Environment; Enzymes; Exocrine pancreas; Faculty; Fellowship; Genes; Genetic Engineering; Grant; Islets of Langerhans; Karyotype determination procedure; Knockout Mice; Knowledge; Laboratories; Life; Measures; Medical center; Medicine; Mentors; Mitosis; Morphology; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nuclear; Object Attachment; Ocimum basilicum; PTTG1 gene; Pancreas; Pathogenesis; Phosphorylation; Physicians; Physiological; Pituitary Neoplasms; Protein Isoforms; Proteins; Public Health; RNA Interference; Rate; Regulation; Research; Research Personnel; Research Proposals; Role; Sister Chromatid; Staging; Structure of beta Cell of islet; TP53 gene; Testing; Training; United States; base; career; cellular imaging; cohesin; human PTTG1 protein; interest; islet; male; neoplastic cell; programs; separase; size

DESCRIPTION (provided by applicant): 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 .

描述（由申请人提供）： 糖尿病是美国的一个重大公共卫生问题。胰腺β细胞质量减少或功能失调是大多数类型糖尿病的基础。 Securin（也称为“PTTG”）在细胞分裂过程中调节染色体分离。删除小鼠的 securin 基因会导致雄性动物的 β 细胞质量减少和糖尿病。在这项资助提案中，我的目标是研究 securin 调节 β 细胞质量的机制。具体目的是通过实验检验以下假设：1）Securin 缺失会导致 β 细胞复制的内在缺陷； 2）染色体分离的调节缺陷导致β细胞特异性细胞周期进程异常并抑制β细胞复制； 3) securin 缺失小鼠中 β 细胞新生完整。从这些研究中获得的知识将有助于阐明糖尿病的发病机制。 我目前是加州大学洛杉矶分校 Cedars-Sinai 医学中心内分泌科的研究员，将于 2005 年 6 月完成我的研究金。通过这些研究，我将扩展我对糖尿病发病机制和 β 细胞生物学的了解。在此资助期结束时，我将准备好进行糖尿病发病机制的独立研究，并在学术医学领域追求富有成效的研究生涯。 Cedars-Sinai 医疗中心拥有出色的活跃基础研究和培养医生在学术医学领域独立发展职业的传统。华润上华拥有与我的提案和研究兴趣相关的完善项目，并完全致力于在卓越的学术环境中维持我的研究职业发展。我将受到内分泌系教师的指导，包括我的导师什洛莫·梅尔梅德（Shlomo Melmed）和监督委员会（约翰·亚当斯博士和巴兹尔·拉波波特博士）。基于我广泛的基础和临床培训，我希望在完成 K08 资助后成为一名独立的内分泌研究员。