SLAM Gene Family Controlled Pathways to SLE

SLAM 基因家族控制 SLE 通路

• 批准号: 7920860
• 负责人: CORNELIS P TERHORST
• 金额: $ 134.78万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920860
• 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 SLAMFamily 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. 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）：该计划项目资助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。我们提出了一个应用程序中的SLAM家族基因在系统性红斑狼疮的发病机制中的作用进行研究，该应用程序名为：“SLAM基因家族控制的SLE通路”。由于成功的初步分析病人的材料和令人兴奋的发现，在基因改变的小鼠，本申请旨在确定如何在信号转导通路的缺陷引起的SLAM家族基因座的变异基因有助于SLE的发病机制。我们将利用我们最近获得的对SLE原因的见解，开展以下三个相互关联的项目和两个支持核心： 项目1。在人类染色体1 q23上的SLAM基因座中鉴定SLE的致病等位基因。 蒙特利尔大学、麻省理工学院布罗德研究所、哈佛和哈默史密斯医院/帝国理工学院伦敦的John Rioux和Tim Vyse。 项目2.小鼠SLE中SLAM受体家族通路的遗传解剖 考克斯特霍斯特，贝斯以色列女执事医疗中心。 项目3。小鼠SLE中CD 48/CD 244受体/配体对的功能分析 阿琳夏普，哈佛医学院病理学系和伊薇特 莱奇曼，华盛顿大学西雅图。 核心A。基因小鼠核心 王宁海，贝斯以色列女执事医疗中心。 核心B。行政核心，考克斯特霍斯特，贝丝以色列女执事医疗中心。 该计划中提出的实验应该一起阐明一个或几个SLAM家族基因如何控制对染色质和其他细胞内成分的耐受性，从而控制对人类和小鼠狼疮的易感性。这些研究的结果应建议可应用于SLE患者的治疗策略。 项目1。在人类染色体1 q23上的SLAM基因座中鉴定SLE的致病等位基因。 蒙特利尔大学、麻省理工学院布罗德研究所、哈佛和哈默史密斯医院/帝国理工学院伦敦的John Rioux和Tim Vyse。 项目2.小鼠SLE中SLAM受体家族通路的遗传解剖 考克斯特霍斯特，贝斯以色列女执事医疗中心。 项目3。小鼠SLE中CD 48/CD 244受体/配体对的功能分析 阿琳夏普，哈佛医学院病理学系和伊薇特 莱奇曼，华盛顿大学西雅图。 核心A。基因小鼠核心 王宁海，贝斯以色列女执事医疗中心。 核心B。行政核心，考克斯特霍斯特，贝丝以色列女执事医疗中心。 该计划中提出的实验应该一起阐明一个或几个SLAM家族基因如何控制对染色质和其他细胞内成分的耐受性，从而控制对人类和小鼠狼疮的易感性。这些研究的结果应建议可应用于SLE患者的治疗策略。