MOLECULAR GENETICS OF COAGULATION DISORDERS

凝血和血栓形成调节的异常在 在许多心、肺和血液的发病机制中起主要作用 疾病。该计划项目将整合一个 探索其分子基础的独立调查人员数量 部分凝血和血栓形成障碍及其作用 血管疾病发病机制中的止血平衡。PPG构建 关于密歇根大学在人类方面的现有实力 分子遗传学与血液细胞分子生物学 凝结。本建议书中的个别项目强调 利用新技术提供更好的生物洞察力和 开发治疗出血、血栓形成及相关疾病的新疗法 心血管疾病。此文件中包含的4个单独项目 PPG将：1)应用转基因动物模型研究因子V 2)探讨内质网加工在凝血中的作用 FVIII和Fv的生物合成及其分子基础的鉴定 因子V和因子的结合不足；3)应用遗传 研究PAI-1在血管系统中的功能及其在血管中的作用的模型 动脉粥样硬化的发病机制；4)研究血管紧张素转换酶的调节 动脉损伤部位的纤溶作用。PPG将支持 3个核心的开发：a)小鼠凝血实验室核心； B)DNA核心；；c)PPG的目标是增加互动和 各项目参与者之间以及项目参与者之间的协作 密歇根大学的大量其他实验室 已从事凝血、血栓和血管方面的研究 疾病。我们预计整个计划的结果是 所有参与者的共同努力将大大超过 单独的部件。

Abnormalities in the regulation of coagulation and thrombosis play a major role in the pathogenesis of many heart, lung, and blood diseases. This program project will integrate the research efforts of a number of independent investigators to explore the molecular basis for selected disorders of coagulation and thrombosis and the role of hemostatic balance in vascular disease pathogenesis. The PPG builds on the existing strength at the University of Michigan in human molecular genetics and cell and molecular biology of blood coagulation. The individual projects in this proposal emphasize the use of new technologies to provide improved biologic insight and develop new treatments for hemorrhage, thrombosis and related cardiovascular disorders. The 4 individual projects contained in this PPG will: 1) apply transgenic animal models to study factor V function in vivo; 2) explore the role of ER processing in coagulation FVIII and FV biosynthesis and identify the molecular basis for combined deficiency of factor V and factor VIII; 3) apply genetic models to study PAI-1 function in the vasculature and its role in the pathogenesis of atherosclerosis; and 4) study the regulation of fibrinolysis at sites of arterial injury. The PPG will support the development of 3 cores: A) the Mouse Coagulation Laboratory core; B) the DNA core; ; C) The PPG will aim to increase interaction and collaboration between individual project participants, as well as among the large number of other laboratories at the University of Michigan already engaged in research on coagulation, thrombosis and vascular disease. We anticipate that the overall program resulting from the combined efforts of all participants will significantly exceed the sum of individual parts.