Fibrinolysis Dysfunction Impact on Graft Function in Liver Transplantation

肝移植中纤溶功能障碍对移植物功能的影响

• 批准号: 10445405
• 负责人: Hunter B Moore
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445405
• 关键词: Academic Medical Centers; Allografting; Attenuated; Automobile Driving; Award; Basic Science; Biological Markers; Biomedical Engineering; Blood Coagulation Disorders; Characteristics; Clinical; Clinical Research; Coagulation Process; Colorado; Complex; Costs and Benefits; Data; Databases; Donor person; Environment; Equilibrium; Extramural Activities; Failure; Fellowship; Fellowship Program; Fibrinolysis; Functional disorder; Funding; Goals; Grant; Health; Healthcare Systems; Impairment; Intensive Care Units; K-Series Research Career Programs; Laboratories; Lead; Liver; Liver diseases; Longevity; Mass Spectrum Analysis; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Operative Surgical Procedures; Organ; Organ Donations; Organ Donor; Organ failure; Outcome; Parents; Patient-Focused Outcomes; Patients; Physicians; Proteins; Proteome; Proteomics; Public Health Schools; Registries; Research; Research Personnel; Resistance; Risk; Role; Running; Scientist; Source; Surgeon; Techniques; Testing; Therapeutic; Therapeutic Intervention; Thrombophilia; Thrombosis; Time; Tissues; Training; Translating; Transplant Recipients; Transplantation; Transplantation Surgery; Trauma; United States; United States National Institutes of Health; Universities; Visceral; base; career; clinical practice; clinical translation; effective therapy; experience; graft function; improved; insight; interest; liver transplantation; longitudinal analysis; medical schools; model building; mortality; multidisciplinary; novel; patient oriented research; prevent; preventable death; professor; prospective; proteomic signature; severe injury; success; therapeutic target

PROJECT SUMMARY/ABSTRACT This is an application for a K99 award for Dr. Hunter Moore, a transplant surgery fellow at the University of Colorado School of Medicine. Dr. Moore is establishing himself as a young investigator in patient-oriented research with a translational focus on fibrinolysis and organ failure. This K99 award will provide him with the mentored support necessary to accomplish the following goals; 1) Establishing a prospective outcome registry to identify variables associated with graft dysfunction, 2) Training in advanced basic science methodologies of quantifying fibrinolysis, 3) Integration of clinical and translation data to form a mechanistic hypothesis for factors driving low fibrinolysis 4) Concurrent success in clinical training with maturation as a physician scientist. Dr. Moore is supported by an expert multidisciplinary mentor team. Dr. Mitch Cohen will be his primary mentor; he is a former K-08 recipient, and currently mentors three additional K award recipients. Dr. Cohen has been researching coagulopathy for decades and currently runs a large NIH and DoD funded lab while serving as the Chair of Surgery at an academic medical center. He will provide mentoring on establishing a successful translational coagulation-based laboratory in addition to balancing clinical and research endeavors. Dr. Moore has two basic science mentors: (1) Dr. Kirk Hansen, a recognized expert on mass spectrometry; he has developed methods for defining tissue-specific proteomics, which will provide novel research approaches to understand fibrinolysis at a local level, (2) Dr. Keith Neeves, an expert on flow-based coagulation; his bioengineering expertise provides the mentorship for building models that simulate the microvasculature. Dr. Angela Sauaia is a Professor in the School of Public Health, with extensive experience in translational coagulation research; she will act as a mentor in building an outcomes database focused on graft function. Her expertise in analyzing longitudinal data and variable reduction techniques will be critical for training Dr. Moore in examining the temporal changes in fibrinolysis over time in the recipient, as well as the complex interactions between the donor and recipient. The final core mentor is Dr. Trevor Nydam, who completed his transplant fellowship at the University of Colorado and is the current fellowship program director. His insight in clinical responsibilities and research are critical for success. Drs. Nydam and Moore will meet monthly and adjust protected research and clinical training as needed to reach milestones in the parent application. Dr. Moore will investigate the association of low fibrinolysis and microvascular clots in the organs of donors for Aim 1, followed by Aim 2, defining the association between low fibrinolysis and impaired early graft function in liver transplant recipients. Aim 3 will assess the donor organ local proteomes effect on forming fibrinolysis resistant clots. These aims will provide insight on the interaction of the door, organ, and recipients driving microvascular thrombosis, enabling the formation of a mechanistic hypothesis to be tested in the R00 maturation of this grant.

项目总结/摘要 这是亨特摩尔博士的K99奖申请书，他是纽约大学的移植手术研究员。 科罗拉多医学院。摩尔博士正在建立自己作为一个年轻的研究人员在病人为导向 以纤维蛋白溶解和器官衰竭为重点的翻译研究。K99奖将为他提供 完成以下目标所需的指导支持：1）建立前瞻性结局登记 识别与移植物功能障碍相关的变量，2）高级基础科学方法学培训， 定量纤维蛋白溶解，3）整合临床和翻译数据以形成用于以下的机制假设： 4）临床培训的成功与作为一名医生科学家的成熟同时发生。 博士摩尔是由一个专家多学科导师团队的支持。米奇·科恩博士将是他的主要导师; 他是前K-08获得者，目前指导另外三名K奖获得者。科恩医生 研究凝血病几十年，目前运行一个大型NIH和国防部资助的实验室，同时作为 一个学术医疗中心的外科主任。他将为建立一个成功的 除了平衡临床和研究工作之外，还可以建立基于凝固的转化实验室。摩尔医生 有两个基础科学导师：（1）柯克汉森博士，公认的质谱专家;他有 开发了定义组织特异性蛋白质组学的方法，这将提供新的研究方法， 了解纤维蛋白溶解在当地一级，（2）博士基思内维斯，专家对流动为基础的凝血;他的 生物工程专业知识为建立模拟微血管系统的模型提供指导。博士 Angela Sauaia是公共卫生学院的教授，在翻译方面拥有丰富的经验， 凝血研究;她将作为导师，建立一个专注于移植功能的成果数据库。她 纵向数据分析和变量缩减技术方面的专业知识对于培训摩尔博士至关重要 在检查受者中纤维蛋白溶解随时间的时间变化，以及复杂的相互作用时， 在捐赠者和接受者之间。最后一位核心导师是完成移植手术的特雷弗·尼达姆医生 他是科罗拉多大学的奖学金获得者，现任奖学金项目主任。他对临床的洞察力 责任和研究是成功的关键。Nydam博士和摩尔博士将每月会面 根据需要保护研究和临床培训，以达到母申请中的里程碑。摩尔医生会 研究供者器官中低纤溶和微血管凝块的相关性， 其次是目标2，定义低纤溶与肝脏早期移植功能受损之间的关系 移植接受者目的3探讨供体器官局部蛋白质组在纤溶抵抗形成中的作用 血栓这些目标将提供关于门、器官和受体之间相互作用的见解， 血栓形成，使形成一个机制的假设进行测试，在R 00成熟的这个赠款。