Using Microfluidics to Identify Mechanisms of Platelet Dysfunction and Assess Therapeutic Efficacy in Traumatic Hemorrhage

使用微流控技术识别血小板功能障碍的机制并评估外伤性出血的治疗效果

• 批准号: 10351512
• 负责人: Susan Marguerite Shea
• 金额: $ 12.91万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-05 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10351512
• 关键词: Address; Admission activity; Age-Years; Agonist; Biological; Biological Assay; Biomedical Engineering; Bleeding time procedure; Blood Platelets; Blood Vessels; Blood specimen; Caring; Cause of Death; Cessation of life; Clinical; Clinical Trials; Clot retraction; Coagulation Process; Data; Development; Doctor of Philosophy; End Point Assay; Ensure; Etiology; Five-Year Plans; Functional disorder; Funding; Goals; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospitalization; Hour; In Vitro; Individual; Injury; Institution; Interdisciplinary Study; Kinetics; Knowledge; Lead; Licensing; Measures; Mediator of activation protein; Mentors; Mentorship; Metabolic; Microfluidics; Microscopy; Mission; Modeling; Molecular; Morphology; National Heart, Lung, and Blood Institute; Outcome; Patients; Phenotype; Physiological; Plasma; Platelet Transfusion; Porosity; Productivity; Recording of previous events; Research; Research Personnel; Resources; Resuscitation; Risk; SELP gene; Sampling; Signal Transduction; Structure; Surface; Technical Expertise; Temperature; Testing; Therapeutic; Time; Transfusion; Translational Research; Trauma; Trauma patient; Traumatic Hemorrhage; Traumatic injury; Treatment Efficacy; United States; United States National Institutes of Health; Universities; Venous; Washington; Work; aged; blood product; clinical development; clinical efficacy; experience; innovation; insight; medical schools; mortality; mortality risk; novel; platelet function; platelet phenotype; point of care; pre-clinical assessment; preclinical study; prevent; preventable death; programs; ratiometric; receptor; success; synergism; therapy development; tool; transfusion medicine; translational scientist; trauma induced coagulopathy

Using Microfluidics to Identify Mechanisms of Platelet Dysfunction and Assess Therapeutic Efficacy in Traumatic Hemorrhage Project Summary/Abstract This proposal consists of a five-year plan to develop Susan M. Shea, PhD into an independent translational scientist in the field of trauma-induced coagulopathy (TIC) and therapeutic assessment of hemostatic blood products. Washington University School of Medicine (WUSM) is an outstanding institution for Dr. Shea to establish her research program, as there is a longstanding history of NIH-funded research, as well as both breadth and depth of resources available. Additionally, there is a high level of synergy and multidisciplinary collaboration among departments, and with other institutions, both of which are manifested in Dr. Shea’s proposed mentoring team and advisory panel. A structured educational program is proposed to provide Dr. Shea with additional knowledge, technical skills, grantsmanship, networking, and mentorship required to achieve a successful transition to independence. Dr. Shea’s immediate goal is to fulfill the aims outlined in this proposal. Trauma is the most common cause of death in the United States in individuals less than 46 years of age, to include 30,000 deaths from hemorrhage per year that could be prevented with more timely and appropriate care. TIC occurs in 25% of trauma patients and is associated with a 4 fold risk of mortality. Platelet dysfunction is one of the main etiologies of TIC, and is a poorly understood phenomenon. TIC-related platelet dysfunction is challenging to study as current clinical assays are not physiologically relevant to hemostatic function. Furthermore, the optimal therapeutic approach to address TIC-related platelet dysfunction is unknown. The aims of Dr. Shea’s research in this proposal include the following: 1. Characterize trauma-induced coagulopathy (TIC)-related platelet dysfunction in the context of global hemostasis and its association with mortality. 2. Define the relative contributions of cellular and soluble mediators to TIC-related platelet dysfunction. 3. Determine which transfusion strategies are effective at reversing platelet dysfunction in TIC. The knowledge gained from the successful effectuation of these aims will result in novel insight into mechanisms of trauma-induced platelet dysfunction and therapeutic efficacy. This will be the first time resuscitation of TIC will be investigated in a microfluidic model of bleeding. Such a platform has the potential to be used for licensing of hemostatic blood products, adjuncts, and agents, as well as to provide the biologic rationale for the development of clinical trials that can assess the clinical efficacy of hemostatic products. This proposal is directly relevant to National Heart, Lung, and Blood Institute (NHLBI) mission, as the long-term objective is to use a biofidelic model of hemostasis to define the mechanisms of and develop therapies for TIC-related platelet dysfunction.

使用微流体识别血小板功能障碍的机制并评估治疗功效 创伤性出血 项目摘要/摘要 该提案包括一项五年计划，将Susan M. Shea，博士发展成独立的翻译 创伤引起的凝血病（TIC）和止血的治疗评估的科学家 华盛顿大学医学院（WUSM）是Shea博士的出色机构 建立她的研究计划，因为NIH资助的研究历史悠久 可用资源的广度和深度。此外，还有高水平的协同作用和多学科 部门之间以及与其他机构之间的合作，这两者都体现在Shea博士的 拟议的心理团队和咨询小组。提出了一个结构化的教育计划，以提供Shea博士 凭借其他知识，技术技能，授予技巧，网络和精神统治才能实现 成功过渡到独立。 Shea博士的近期目标是实现该提案中概述的目标。创伤是最常见的原因 美国的死亡人数不到46岁，包括出血30,000人死亡 每年可以通过更及时和适当的护理来预防。 TIC发生在25％的创伤患者中 并与4倍死亡的风险有关。血小板功能障碍是TIC的主要病因之一，是 知识不足的现象。挑战与TIC相关的血小板功能障碍作为当前的临床研究 测定与止血功能无关。此外，最佳的治疗方法 地址与TIC相关的血小板功能障碍尚不清楚。 Shea博士在此提案中的研究的目的包括 下列： 1。在创伤引起的凝血病（TIC）相关的血小板功能障碍中表征 全球止血及其与死亡率的关联。 2。定义细胞和固体介体对TIC相关血小板的相对贡献 功能障碍。 3。确定哪些输血策略可有效逆转TIC中的血小板功能障碍。 从这些目标的成功效果中获得的知识将导致对机制的新见解 创伤引起的血小板功能障碍和治疗效率。这将是TIC首次复苏 在出血的微流体模型中进行研究。这样的平台有可能用于许可 止血产物，辅助药和药物，以及为发育提供生物学原理 可以评估止血产物的临床效率的临床试验。该建议与 国家心脏，肺和血液研究所（NHLBI）任务，作为长期目标是使用生物层模型 止血的定义和发展与TIC相关血小板功能障碍的疗法的机理。