MOLECULAR GENETICS OF COAGULATION DISORDERS

在凝血和血栓形成的调节中发挥着重要作用。 在许多心脏、肺和血液疾病的发病机制中起主要作用 疾病 该计划项目将整合一个 一些独立的研究人员探索分子基础， 某些凝血和血栓形成疾病以及 止血平衡在血管疾病发病机制中的作用。 PPG构建 密歇根大学现有的人力资源 血液的分子遗传学和细胞分子生物学 凝血 本提案中的各个项目强调 使用新技术，以提供更好的生物学洞察力， 开发出血、血栓形成及相关疾病的新疗法 心血管疾病 其中包含的4个项目 PPG将：1）应用转基因动物模型研究因子V 2）探讨ER加工在凝血过程中的作用 FVIII和FV的生物合成，并确定其分子基础 因子V和因子VIII的联合缺乏; 3）应用遗传学 研究派-1在血管系统中的功能及其在 动脉粥样硬化的发病机制; 4）研究 动脉损伤部位的纤维蛋白溶解。 PPG将支持 开发3个核心：A）小鼠凝血实验室核心; B）DNA核心; C）PPG旨在增加相互作用， 项目参与者之间以及 密歇根大学的大量其他实验室 已经从事凝血、血栓形成和血管 疾病 我们预计，整个计划产生的 所有参与者的共同努力将大大超过 单独的部分。

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.