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: 10563154
• 负责人: Susan Marguerite Shea
• 金额: $ 12.82万
• 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/10563154
• 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; Education; 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; Licensing; Measures; Mediator; Mentors; Mentorship; Metabolic; Microfluidics; Microscopy; Mission; Modeling; Molecular; Morphology; National Heart, Lung, and Blood Institute; Outcome; Patients; Perfusion; 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.

应用微流体技术研究血小板功能障碍的机制及疗效评价