Mechanisms of normal and abnormal platelet homeostasis

正常和异常血小板稳态的机制

基本信息

批准号：
7808883
负责人：
Joel S. Bennett
金额：
$ 247.75万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-27 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7808883
关键词：
Mechanisms normal abnormal platelet homeostasis

项目摘要

Thrombotic disorders are among the most common diseases encountered in clinical medicine and are the leading causes of morbidity and mortality in the United States. Platelets play an essential role in the pathogenesis of these diseases because platelet aggregates are responsible for the vaso-occulsive events that puncuate their clinical course. Thus, the focus of this SCCOR in Hemostasis and Thrombosis, entitled "Mechanisms of Normal and Abnormal Platelet Homeostasis", is on related clinical and basic aspects of platelet biology, taking advantage of the extensive experience of investigators at the University of Pennsylvania in these areas of investigation. The SCCOR consists of 3 clinical and 3 basic research projects, plus 2 supporting core units. Project 1, entitled "Understanding the mechanistic basis of heparin-induced thrombocytopenia (HIT)", tests the hypothesis that variations in platelet factor 4 (PF4) secretion are responsible for the variable incidence and clinical manifestations of HIT. Project 2, entitled "Immunobiology of immune-mediated thrombocytopenias" studies the nature of autoantibody responses in patients with ITP, HIT, and TTP. Project 3, entitled "Clinical aspects of aspirin and clopidogrel resistance", addresses the stability, specificity and incidence of the "aspirin resistant" phenotype, defines novel lipidomic and proteomic signatures of aspirin resistance, and relates conventional and novel biomarkers of the phenotype to clinical outcome. Project 4, entitled "Role of pleckstrin in platelet activation", is focused on phospholipid-mediated signaling pathways and the role they play in signaling in platelets and other cells of hematopoietic origin. Project 5, entitled "The role of Sema4D/CD100 and its receptors in platelet biology and thrombosis", studies the role of platelet sema4D/CD100 and its receptors in platelet function and tests the use of soluble sema4D/CD100 as a biomarker for thrombotic events. Project 6, entitled "Regulation of platelet integrin function", continues to study the conformational changes that regulate integrin activation states, focusing on the platelet fibrinogen receptor allb-beta-3. The projects are supported by a Bioinformatics Core to store and analyze clinical data and by a Core for Administration.

血栓性疾病是临床医学中最常见的疾病之一，也是美国发病和死亡的主要原因。血小板在这些疾病的发病机制中发挥着重要作用，因为血小板聚集是导致其临床过程中出现的血管闭塞事件的原因。因此，此次止血和血栓形成 SCCOR 题为“正常和异常血小板稳态的机制”，重点关注血小板生物学的相关临床和基础方面，利用宾夕法尼亚大学研究人员在这些领域的丰富经验的调查。 SCCOR由3个临床项目和3个基础研究项目以及2个支持核心单位组成。项目 1 题为“了解肝素诱导的血小板减少症 (HIT) 的机制基础”，测试了血小板因子 4 (PF4) 分泌的变化导致 HIT 的不同发病率和临床表现的假设。项目 2 题为“免疫介导的血小板减少症的免疫生物学”，研究 ITP、HIT 和 TTP 患者自身抗体反应的性质。项目 3 题为“阿司匹林和氯吡格雷耐药的临床方面”，解决了“阿司匹林耐药”表型的稳定性、特异性和发生率，定义了阿司匹林耐药的新型脂质组学和蛋白质组学特征，并将该表型的常规和新型生物标志物与临床联系起来。结果。项目 4 题为“pleckstrin 在血小板激活中的作用”，重点研究磷脂介导的信号传导途径及其在血小板和其他造血来源细胞信号传导中所发挥的作用。项目5题为“Sema4D/CD100及其受体在血小板生物学和血栓形成中的作用”，研究血小板sema4D/CD100及其受体在血小板功能中的作用，并测试可溶性sema4D/CD100作为血栓事件生物标志物的用途。项目6题为“血小板整合素功能的调节”，继续研究调节整合素激活状态的构象变化，重点关注血小板纤维蛋白原受体allb-beta-3。这些项目由用于存储和分析临床数据的生物信息学核心和用于管理的核心支持。