Mechanisms of normal and abnormal platelet homeostasis

正常和异常血小板稳态的机制

• 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
• 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; Mechanisms; normal; abnormal; platelet; homeostasis

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，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理中起着至关重要的作用，因为血小板聚集体是导致其临床病程的血管 - 切除事件的原因。因此，这种SCCOR在止血和血栓形成中的重点，标题为“正常和异常血小板稳态的机制”，是利用宾夕法尼亚大学在这些调查领域的宾夕法尼亚大学研究人员的丰富经验的相关临床和基本方面。 SCCOR由3个临床和3个基础研究项目组成，以及2个支持核心单位。项目1的标题为“了解肝素诱导的血小板减少症的机理基础（hit）”，检验了以下假设：血小板因子4（PF4）分泌的变化是造成命中的变化和临床表现的原因。项目2，标题为“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的标题为“阿司匹林和氯吡格雷耐药性的临床方面”，涉及“阿司匹林抗药性”表型的稳定性，特异性和发生率，定义了阿司匹林耐药性的新型脂肪组和蛋白质组学特征，并将表型的常规生物标志物与临床成果相关。项目4，名为“ Pleckstrin在血小板激活中的作用”，重点是磷脂介导的信号通路及其在造血起源的血小板和其他细胞中所起的作用。项目5的标题为“ SEMA4D/CD100及其受体在血小板生物学和血栓形成中的作用”，研究了血小板SEMA4D/CD100及其受体在血小板功能中的作用，并测试了可溶性SEMA4D/CD100作为血栓事件的生物标志物的使用。项目6，标题为“血小板整合素功能的调节”，继续研究调节整联蛋白激活状态的构象变化，重点是血小板纤维蛋白原受体Allb-beta-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以及管理核心。