Molecular Genetics of Coagulation Disorders

凝血障碍的分子遗传学

• 批准号: 7657103
• 负责人: Daniel A Lawrence
• 金额: $ 20.12万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7657103
• 关键词: A Mouse; Anticoagulants; Antigens; Atherosclerosis; Biological Assay; Blood Coagulation Disorders; Cells; Chemicals; Coagulation Process; Ensure; Fibrin fragment D; Genomics; Goals; Individual; Inflammatory; Inflammatory Response; Laboratories; Laboratory mice; Lipids; Liver; Measures; Metabolic; Molecular Genetics; Mouse Protein; Mus; Plasma; Research Personnel; Screening procedure; Streptococcal Infections; Streptococcus pyogenes; Streptokinase; Stress; TFPI; Technology; Thrombosis; Virulence Factors; adipokines; antithrombin III-protease complex; base; cytokine; inhibitor/antagonist; programs; prothrombin fragment 1; response; small molecule; success

Core A: Mouse Coagulation Laboratory The Mouse Coagulation Laboratory Core A has the goal to serve every project in the Program. It will provide an array of assays assessing coagulation, and anticoagulant activities, as well as plasma lipid profiles. The Core will also provide assays of inflammatory cytokines and of adipokines, using a mutiplex format with the Luminex Technology. Core A will also use established kits for mouse proteins associated with thrombosis, and atherosclerosis. The specific assays that are available for each of the projects are indicated below. Core A will also coordinate the high through-put screening of small molecules by the Center for Chemical Genomics. Project 1: Core A will perform standard clotting analysis of murine plasma, assays will include FV activity and antigen, APC activity, TFPI activity, D-Dimer, thrombin-antithrombin complex and prothrombin fragment 1+2 assays. Assays of Adamts13 activity will also be performed. Project 2: Core A will evaluate the effect of FVIII expression on ER stress in the liver. Assays will include FVIII activity and antigen, and analysis of inflammatory responses as well as adipokine/cytokine profiles, and metabolic parameters such as lipid profiles. Project 2 will use the CCG component of Core A to screen for small molecule inhibitors of CHOP using unique cell-based assays developed by the Kaufman Laboratory. Project 3: Core A will assist the investigators of Project 3 by measuring plasma cytokine levels in studies of the murine response to Group A Streptococcal infection using a mutiplex format with the Luminex Technology. Project 3 will also use the CCG component of Core A to screen for small molecule inhibitors of Group A Streptococcus virulence factors such as streptokinase. The overall goals of Core A are to enhance the success of each individual project by providing rigorous, standardized assays and to ensure that the combined Program is stronger than each of its individual parts.

核心A：小鼠凝血实验室 小鼠凝血实验室核心 A 的目标是为该计划中的每个项目提供服务。它将提供 一系列评估凝血、抗凝活性以及血浆脂质谱的测定。这 Core 还将使用多重格式提供炎症细胞因子和脂肪因子的检测 鲁米尼克斯科技。 Core A 还将使用已建立的试剂盒来检测与血栓形成相关的小鼠蛋白， 和动脉粥样硬化。下面列出了每个项目可用的具体检测方法。核 A还将协调化学中心对小分子的高通量筛选 基因组学。 项目 1：Core A 将执行鼠血浆的标准凝血分析，检测将包括 FV 活性 和抗原、APC 活性、TFPI 活性、D-二聚体、凝血酶-抗凝血酶复合物和凝血酶原片段 1+2 测定。还将进行 Adamts13 活性测定。 项目 2：核心 A 将评估 FVIII 表达对肝脏 ER 应激的影响。化验将包括 FVIII 活性和抗原，以及炎症反应和脂肪因子/细胞因子谱的分析，以及 代谢参数，例如血脂谱。项目2将使用Core A的CCG组件来筛选 使用考夫曼实验室开发的独特的基于细胞的测定法来检测 CHOP 的小分子抑制剂。 项目 3：核心 A 将通过测量血浆细胞因子水平来协助项目 3 的研究人员 使用 Luminex 的多重形式观察小鼠对 A 组链球菌感染的反应 技术。项目3还将利用Core A的CCG组件来筛选以下药物的小分子抑制剂： A组链球菌的毒力因子如链激酶。 核心 A 的总体目标是通过提供严格的、 标准化测定并确保组合程序比其各个单独部分更强。