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）：该计划项目赠款应用程序汇集了一组研究人员，这些研究人员是分子和细胞免疫学领域以及人类和小鼠遗传学领域的专家。我们建议研究大型基因在系统性红斑狼疮的发病机理中的作用，该应用程序的标题为：“ SLAM基因家族控制的SLE途径”。由于对患者材料进行了成功的初步分析以及在遗传上改变的小鼠中的令人兴奋的发现，因此该应用程序旨在定义由大型基因座的变异基因引起的信号转导途径的缺陷如何有助于SLE的发病机理。在以下三个相关项目和两个支持核心的情况下，我们将使用最近获得的见解对SLE的原因： 项目1。在人类染色体1Q23上确定SLE的因果等位基因。 约翰·里奥克斯（John Rioux）和蒂姆·维斯（Tim Vyse），蒙特利尔大学，麻省理工学院和哈默史密斯医院 /伦敦帝国学院。 项目2。鼠SLE中的大蛋白酶家庭途径的遗传解剖。 考克斯·特霍斯特（Cox Terhorst），贝丝以色列执事医疗中心。 项目3。鼠SLE中CD48/CD244受体/配体对的功能分析。 哈佛医学院和伊维特病理学系Arlene Sharpe 华盛顿大学西雅图大学洛奇曼。 核A.遗传小鼠核心 Ninghai Wang，贝丝以色列执事医疗中心。 核心B.行政核心，考克斯·特霍斯特（Cox Terhorst），贝丝以色列执事医疗中心。 程序中提出的实验应阐明一个或几个大满贯家族基因如何控制对染色质和其他细胞内成分的耐受性，从而对人和鼠狼疮的敏感性。这些研究的结果应建议可以应用于SLE患者的治疗策略。