Mechanisms of normal and abnormal platelet homeostasis

正常和异常血小板稳态的机制

• 批准号: 6951697
• 负责人: Joel S. Bennett
• 金额: $ 236.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/6951697
• 关键词: clinical research; platelet activation; platelet disorder

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：血栓性疾病是临床医学中最常见的疾病之一，是美国发病率和死亡率的主要原因。血小板在这些疾病的发病机制中起着重要作用，因为血小板聚集体是导致血管闭塞事件的原因，而血管闭塞事件是导致这些疾病的临床过程的原因。因此，本SCCOR的止血和血栓形成，题为“机制正常和异常血小板稳态”，是在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的研究人员在这些领域的调查的广泛经验。SCCOR包括3个临床和3个基础研究项目，以及2个支持核心单元。项目1，题为“了解肝素诱导的血小板减少症（HIT）的机制基础"，测试血小板因子4（PF 4）分泌的变化是HIT的可变发生率和临床表现的原因这一假设。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抵抗的临床方面”，阐述了“阿司匹林抵抗”表型的稳定性、特异性和发生率，定义了阿司匹林抵抗的新型脂质组学和蛋白质组学特征，并将表型的常规和新型生物标志物与临床结果相关联。项目4，题为“Pleckstrin在血小板活化中的作用”，重点是磷脂介导的信号传导途径及其在血小板和其他造血细胞中的信号传导作用。项目5题为“Sema 4D/CD 100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sema 4D/CD 100及其受体在血小板功能中的作用，并测试可溶性sema 4D/CD 100作为血栓形成事件生物标志物的用途。项目6题为“血小板整联蛋白功能的调节”，继续研究调节整联蛋白活化状态的构象变化，重点是血小板纤维蛋白原受体allb-β-3。这些项目得到了生物信息学核心的支持，以存储和分析临床数据，并得到管理核心的支持。