Molecular & Cellular Mechanisms in Transfusion Medicine

描述（由申请人提供）：本申请为HL-44612项目拨款21-25年的竞争性续期申请，为输血医学领域重要的分子和细胞机制的协调、多学科研究提供支持。我们的申请反映了十多年来项目负责人之间持续的密切合作关系，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PROJECT 1中，Peter Newman试图研究血小板整合素和itam信号蛋白家族成员之间的合作相互作用，itam信号蛋白家族成员调节血小板活化和粘附，与血栓形成和止血有关，以及血小板储存和输血治疗。在PROJECT 2中，Hartmut Weiler将研究蛋白C通路的元件对造血干细胞存活和归巢的影响，这对细胞治疗领域的发展具有重要意义。项目3。Demin Wang领导的团队，试图确定特定B淋巴细胞群在肝素诱导的血小板减少症的细胞免疫反应中的作用，这些研究可能会改变我们诊断和治疗这种复杂的出血和凝血障碍的能力。PROJECT 4，由Debra Newman领导，提出检测血小板信号转导途径，这些途径对粘附配体的血小板活化反应进行差异调节，希望找到控制血栓形成的新治疗靶点和策略。在PROJECT 5中，Robert Montgomery提出在一系列新的大型和小型动物基因治疗方案中，研究von Willebrand因子指导和稳定因子vll的能力。行政核心将监督和协调该计划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、肽合成、图像分析、组织学、流式细胞术、BIAcore分析和单克隆抗体生产提供集中的仪器和专业知识。转基因/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。综上所述，这些多方合作所提供的思想、试剂和专业知识的整体科学协同作用将使输血医学研究项目能够推进我们对血液和血管细胞生物学的理解，并将研究成果应用于治疗血液疾病和提高现代输血治疗的有效性。

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.