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Post-Injury Platelet Biology: Mechanisms and Outcomes

损伤后血小板生物学：机制和结果

基本信息

批准号：
10468672
负责人：
Lucy Kornblith
金额：
$ 19.91万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468672
关键词：
Address Advisory Committees Affect Basic Science Biological Biological Assay Biological Markers Biology Blood Coagulation Disorders Blood Platelets Blood Vessels California Caring Cause of Death Cessation of life Clinical Clinical Data Clinical Research Coagulation Process Collection Critical Care Data Disease Endothelial Cells Endothelium Enzyme-Linked Immunosorbent Assay Erythrocytes Extramural Activities Flow Cytometry Funding General Hospitals Goals Growth Hemorrhage Homeostasis Impairment In Vitro Inflammation Injury Injury Severity Score Integrins Knowledge Maintenance Measurement Measures Mentored Patient-Oriented Research Career Development Award Mentors Methodology Methods Molecular Morbidity - disease rate Observational Study Operative Surgical Procedures Organ failure Outcome P-Selectin Pathogenesis Pathway interactions Patient-Focused Outcomes Patients Permeability Phenotype Physiological Plasma Platelet Activation Platelet Count measurement Platelet Transfusion Platelet aggregation Population Public Health Research Research Personnel Resuscitation Role San Francisco Scientist Shock Surgeon Testing Training Transfusion Translational Research Trauma Trauma patient Uncertainty Universities Whole Blood base career career development clinical practice cohort effective therapy electric impedance experimental study improved improved outcome in vitro Assay injured innovation interest metropolitan monocyte mortality multidisciplinary patient oriented research platelet phenotype preventable death prospective response response to injury severe injury standard of care syndecan tool translational scientist translational study trauma centers trauma induced coagulopathy von Willebrand Factor

项目摘要

PROJECT SUMMARY/ABSTRACT This is an application for a K23 award for Dr. Lucy Kornblith, a trauma and surgical critical care fellow at the University of California, San Francisco and Zuckerberg San Francisco General Hospital. Dr. Kornblith is establishing herself as a young investigator in patient-oriented research with a translational focus on trauma- induced coagulopathy and its pathogenesis to improve the care of injured patients. This K23 award will provide her with the support necessary to accomplish the following goals: (1) to become an expert translational researcher in post-injury platelet biology as it relates to trauma-induced coagulopathy; (2) to study the drivers, mechanisms, and outcomes of alterations in post-injury platelet biology; and (3) to develop all the tools necessary to have an independent translational research career. Dr. Kornblith is supported by a scientific advisory committee comprised of a multidisciplinary mentoring team of experts: her primary mentor, Dr. Michael Matthay has extensive expertise in prospective observational studies, basic science methodology critical to this proposal, and he is an expert in the career development of early stage investigators; co-mentors are Dr. Mitchell Cohen, a translational researcher who is an expert in the field of trauma-induced coagulopathy, and Dr. Guy Zimmerman, an expert platelet biologist. Her advisory committee includes Dr. Shibani Pati, an expert vascular biologist, and Dr. Alan Hubbard, a biostatistician consultant specializing in causal inference in trauma. Trauma-induced coagulopathy is a central cause of preventable deaths from hemorrhage after injury. The contribution and impact of altered post-injury platelet biology on trauma-induced coagulopathy is not well understood despite the pivotal contribution of platelets to normal coagulation and endothelial integrity. The central hypothesis for this proposal is that severe injury and shock drive altered platelet activation, platelet aggregation, and platelet-endothelial interactions that are associated with increased rates of transfusion, organ failure, and mortality. Dr. Kornblith will investigate these causal pathways, mechanisms, and associated outcomes in a prospective observational trauma cohort through collection of biospecimens and detailed clinical data. This proposal represents an innovative approach to studying post-injury platelet biology because it incorporates methods that have not previously been applied together in trauma populations. Dr. Kornblith will determine the phenotypes of endothelial injury and platelet biology driven by severe injury and shock following trauma (AIM 1), the effect of post-injury platelets on in vitro endothelial permeability (AIM 2), and the morbidity and mortality associated with phenotypes of platelet activation, platelet aggregation, and platelet-endothelial interactions following trauma (AIM 3). The proposal addresses a major gap in our understanding of the role of platelets in trauma-induced coagulopathy, and the training plan it requires will form the basis for a compelling R01 proposal to identify associated molecular mechanisms and the role of platelet transfusions and platelet-based treatments in reduction of morbidity and mortality for hemorrhaging trauma patients.

项目总结/摘要这是一份K23奖的申请，申请人是露西·科恩布利斯博士，她是美国国家创伤和外科重症监护中心的创伤和外科重症监护研究员。加州大学旧金山弗朗西斯科分校和扎克伯格旧金山弗朗西斯科综合医院。Kornblith博士是确立自己作为一个年轻的研究人员在以病人为导向的研究与翻译重点创伤- 诱发性凝血功能障碍及其发病机制，以提高对受伤病人的护理。此次K23奖将提供她与必要的支持，以实现以下目标：（1）成为一个专家翻译创伤后血小板生物学的研究者，因为它与创伤诱导的凝血病有关;（2）研究驱动因素，损伤后血小板生物学改变的机制和结果;（3）开发所有必要的工具拥有独立的翻译研究生涯。科恩布利斯博士得到了一个科学顾问的支持委员会由一个多学科的专家指导团队组成：她的主要导师，迈克尔·马泰博士在前瞻性观察研究方面拥有广泛的专业知识，基础科学方法对这项提议至关重要，他是早期调查人员职业发展方面的专家;共同导师是米切尔·科恩博士，创伤性凝血障碍领域的专家，以及盖伊齐默尔曼博士，血小板生物学家她的顾问委员会包括血管生物学家专家Shibani帕蒂博士，博士艾伦·哈伯德是一位生物统计学家，专门研究创伤因果推理。创伤引起凝血病是可预防的损伤后出血死亡的主要原因。贡献和影响创伤后血小板生物学改变对创伤性凝血功能障碍的影响尚不清楚，血小板对正常凝血和内皮完整性的贡献。这项提议的核心假设是严重损伤和休克驱动改变了血小板活化、血小板聚集和血小板-内皮与输血率、器官衰竭和死亡率增加相关的相互作用。科恩布里斯博士会在前瞻性观察中调查这些因果途径、机制和相关结果。通过收集生物标本和详细的临床数据对创伤队列进行分析。该提案代表了研究损伤后血小板生物学的创新方法，因为它结合了没有以前一起应用于创伤人群。Kornblith博士将确定严重损伤和创伤后休克（AIM 1）导致的内皮损伤和血小板生物学，损伤后血小板对体外内皮通透性（AIM 2）的影响，以及与损伤相关的发病率和死亡率。创伤后血小板活化、血小板聚集和血小板-内皮相互作用的表型 (AIM（3）第三章。该提案解决了我们在理解血小板在创伤诱导的凝血功能障碍，以及它所要求的培训计划将构成一个令人信服的R 01提案的基础，以确定相关的分子机制以及血小板输注和基于血小板的治疗在降低创伤患者的发病率和死亡率。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The National Blood Shortage-An Impetus for Change.

DOI：
10.1097/sla.0000000000005393
发表时间：
2022-04-01
期刊：
Annals of surgery
影响因子：
9
作者：
通讯作者：

"Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury": Reply.

“儿茶酚胺信号传导在创伤后血小板耗竭发展中的重要性”：答复。

DOI：
10.1111/jth.15869
发表时间：
2022
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
0
作者：
Matthay,ZacharyA;Fields,AlexanderT;Kornblith,LucyZ
通讯作者：
Kornblith,LucyZ

Von Willebrand factor as a thrombotic and inflammatory mediator in critical illness.

DOI：
10.1111/trf.15667
发表时间：
2020-06
期刊：
TRANSFUSION
影响因子：
2.9
作者：
Plautz, William E.;Matthay, Zachary A.;Rollins-Raval, Marian A.;Raval, Jay S.;Kornblith, Lucy Z.;Neal, Matthew D.
通讯作者：
Neal, Matthew D.

A case of unexplained duodenal ulcer and massive gastrointestinal bleed.

DOI：
10.1016/j.cca.2020.03.037
发表时间：
2020-07
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
0
作者：
通讯作者：

γ' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity.

DOI：
10.1016/j.bcmd.2023.102746
发表时间：
2023-07
期刊：
BLOOD CELLS MOLECULES AND DISEASES
影响因子：
2.3
作者：
Kornblith, Lucy Z.;Sadhanandhan, Bindhya;Arun, Sreepriya;Long, Rebecca;Johnson, Alicia J.;Noll, Jamie;Ramchand, C. N.;Olynyk, John K.;Farrell, David H.
通讯作者：
Farrell, David H.