Molecular & Cellular Mechanisms in Transfusion Medicine

描述(由申请人提供)：这是21-25年计划资助HL-44612的竞争性续签申请，该计划支持对输血医学领域重要的分子和细胞机制进行协调、多学科的研究。我们的申请反映了十多年来项目负责人之间持续的、密切的合作关系，他们仍然致力于以血液和血管细胞生物学为中心的相关研究项目。在项目1中，Peter Newman试图研究血小板整合素和ITAM家族成员之间的合作相互作用，ITAM家族调节血小板的激活和粘连，与血栓形成和止血以及血小板储存和输血治疗相关。在项目2中，哈特穆特·韦勒将研究蛋白C途径的元素对造血干细胞存活和归巢的影响，并对不断增长的细胞治疗领域产生影响。由Demin Wang领导的项目3旨在确定特定B淋巴细胞群在肝素诱导的血小板减少症潜在的细胞免疫反应中的作用-研究可能改变我们诊断和处理这种复杂的出血和凝血障碍的能力。由黛布拉·纽曼领导的项目4建议研究不同于黏附配体的调节血小板激活反应的血小板信号转导通路，以期确定控制血栓形成的新的治疗靶点和策略。在项目5中，罗伯特·蒙哥马利建议在一系列新的大小动物基因治疗方案中检查von Willebrand因子引导和稳定因子V11的能力。行政核心将监督和协调该方案的日常科学和财政运作。共享仪器核心将继续为DNA序列分析、多肽合成、图像分析、组织学、流式细胞术、Biacore分析和单抗生产提供集中的仪器和专业知识。转基因/基因敲除小鼠核心将协助载体设计、转基因小鼠生产、多性状育种和畜牧业。总而言之，这些多重合作所提供的想法、试剂和专业知识的整体科学协同作用，应该能够使这一输血医学研究计划项目促进我们对血液和血管细胞生物学的理解，并将所取得的成果应用于治疗血液疾病和提高现代输血疗法的有效性。

DESCRIPTION (provided by applicant): This is a competitive renewal application for years 21-25 of Program Project Grant HL-44612, which provides support for a coordinated, multi-disciplinary investigation of molecular and cellular mechanisms important to the field of transfusion medicine. Our application reflects ongoing, close collaborative ties that have existed amongst the Project Leaders for more than a decade, and who remain committed to interrelated research projects centered around the biology of blood and vascular cells. In PROJECT 1, Peter Newman seeks to examine the cooperative interactions between platelet integrins and members of the ITAM-family of signaling proteins that regulate platelet activation and adhesion, with relevance for thrombosis and hemostasis, as well as platelet storage and transfusion therapy. In PROJECT 2, Hartmut Weiler will examine the influence of elements of the Protein C pathway on hematopoietic stem cell survival and homing, with implications for the growing field of cellular therapies. PROJECT 3. led by Demin Wang, seeks to define the role of specific B lymphocyte populations in the cellular immune response underlying heparin-induced thrombocytopenia - studies that may transform our ability to diagnose and manage this complex bleeding and clotting disorder. PROJECT 4, led by Debra Newman, proposes to examine platelet signal transduction pathways that differentially regulate platelet activation responses to adhesive ligands, with hopes of identifying novel therapeutic targets and strategies for controlling thrombus formation. In PROJECT 5, Robert Montgomery proposes to examine the ability of von Willebrand factor to direct and stabilize factor Vlll in a series of novel large- and small-animal gene therapy protocols. The Administrative Core will oversee and coordinate the day-to-day scientific and fiscal operation of the Program. The Shared Instrumentation Core will continue to provide centralized instrumentation and expertise for DNA sequence analysis, peptide synthesis, image analysis, histology, flow cytometry, BIAcore analysis, and monoclonal antibody production. The Transgenic/Knockout Mouse Core will assist with vector design, transgenic mouse production, multi-trait breeding, and animal husbandry. Taken together, the overall scientific synergy of ideas, reagents and expertise afforded by these multiple collaborations should enable this Program Project in Transfusion Medicine Research to advance our understanding of the biology of blood and vascular cells, and to apply findings made toward treating blood diseases and enhancing the effectiveness of modern- day transfusion therapy.