Mechanisms of normal and abnormal platelet homeostasis

描述(申请人提供)：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至关重要的作用，因为血小板聚集体是影响其临床进程的血管闭塞事件的罪魁祸首。因此，这本名为《正常和异常血小板稳态的机制》的止血和血栓SCCOR的重点是相关的临床和基础方面的血小板生物学，利用了宾夕法尼亚大学研究人员在这些研究领域的丰富经验。SCCOR包括3个临床研究项目和3个基础研究项目，外加2个支持核心单位。项目1名为“了解肝素诱导的血小板减少症(HIT)的机制基础”，测试了一种假设，即血小板第4因子(PF4)分泌的变化与HIT的不同发病率和临床表现有关。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”，阐述了“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的脂肪组学和蛋白质组学特征，并将该表型的传统和新型生物标记物与临床结果联系起来。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血小板和其他造血细胞中所起的信号作用。项目5名为“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作为血栓形成事件的生物标志物的用途。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，重点是血小板纤维蛋白原受体Allb-β-3。这些项目得到了一个存储和分析临床数据的生物信息学核心和一个管理核心的支持。

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.