SLAM Gene Family Controlled Pathways to SLE

SLAM 基因家族控制 SLE 通路

• 批准号: 7275918
• 负责人: CORNELIS P TERHORST
• 金额: $ 131.84万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275918
• 关键词: SLAM; Gene; Family; Controlled; Pathways

DESCRIPTION (provided by applicant): This Program Project Grant Application brings together a group of investigators who are experts in the areas of molecular and cellular immunology and human and mouse genetics. We propose to study the role of the SLAM-Family genes in the pathogenesis of Systemic Lupus Erythematosus in an application, which, is entitled: "Slam Gene Family controlled pathways to SLE". Because of successful preliminary analyses of patient materials and exciting findings in genetically altered mice, this application seeks to define how defects in signal transduction pathways caused by variant genes of the SLAM-Family locus contribute to the pathogenesis of SLE. We will use our recently acquired insights into the causes of SLE for the following three interlinked projects and two supporting Cores: Project 1. Identifying the causal alleles for SLE in the SLAM locus on human chromosome 1q23. John Rioux and Tim Vyse, University of Montreal, Broad Institute at MIT and Harvard and Hammersmith Hospital / Imperial College London. Project 2. Genetic dissection of the SLAM-receptor-family pathways in murine SLE. Cox Terhorst, Beth Israel Deaconess Medical Center. Project 3. Functional analyses of the CD48/CD244 receptor/ligand pair in murine SLE. Arlene Sharpe, Department of Pathology of the Harvard Medical School and Yvette Latchman, University of Washington at Seattle. Core A. Genetic Mouse Core Ninghai Wang, Beth Israel Deaconess Medical Center. Core B. Administrative Core, Cox Terhorst, Beth Israel Deaconess Medical Center. Together the experiments that are proposed in the Program should clarify how one or several of the SLAM Family genes control tolerance to chromatin and other intracellular components and consequently susceptibility to human and murine lupus. The results of these studies should suggest therapeutic strategies that can be applied to SLE patients.

描述（由申请人提供）：本计划项目拨款申请汇集了一组研究人员，他们是分子和细胞免疫学以及人类和小鼠遗传学领域的专家。我们建议在一项题为“Slam基因家族控制SLE通路”的申请中研究Slam家族基因在系统性红斑狼疮发病机制中的作用。由于对患者材料的成功初步分析和基因改变小鼠的令人兴奋的发现，本应用程序试图确定由slam -家族位点变异基因引起的信号转导途径缺陷如何促进SLE的发病机制。我们将利用我们最近获得的对SLE病因的见解，开展以下三个相互关联的项目和两个支持核心：