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: 10693828
• 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/10693828
• 关键词: Academic Medical Centers; Allografting; Attenuated; Automobile Driving; Award; Basic Science; Biological Markers; Biomedical Engineering; Blood Coagulation Disorders; Blood Vessels; Characteristics; Clinical; Clinical Research; Coagulation Process; Colorado; Complex; Costs and Benefits; Data; Databases; Donor person; Environment; 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; Liver; 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; Research Training; Resistance; Risk; Role; Running; Scientist; Source; Surgeon; Techniques; Testing; Therapeutic; Therapeutic Intervention; Thrombophilia; Thrombosis; Time; Tissues; Training; Translating; Translations; Transplant Recipients; Transplantation; Transplantation Surgery; Trauma; United States; United States National Institutes of Health; Universities; Visceral; career; clinical practice; clinical training; effective therapy; end stage liver disease; experience; graft dysfunction; 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/文摘

项目成果

Low viscoelastic clot strength, platelet transfusions, and graft dysfunction are associated with persistent postoperative ascites following liver transplantation.

• DOI: 10.1016/j.amjsurg.2022.09.054
• 发表时间: 2022-12
• 期刊: AMERICAN JOURNAL OF SURGERY
• 影响因子: 3
• 作者: Jiang, Jessie G.;Ferrell, Tanner;Sauaia, Angela;Rodriguez, Ivan E.;Yoeli, Dor;Nydam, Trevor L.;Kennealey, Peter T.;Pomposelli, James J.;Pomfret, Elizabeth A.;Moore, Hunter B.
• 通讯作者: Moore, Hunter B.

Fibrinolysis resistance after liver transplant as a predictor of early infection.

• DOI: 10.1016/j.amjsurg.2022.09.011
• 发表时间: 2022-12
• 期刊: AMERICAN JOURNAL OF SURGERY
• 影响因子: 3
• 作者: Rodriguez, Ivan E.;Yoeli, Dor;Ferrell, Tanner;Jiang, Jessie G.;Truong, Ronald;Nydam, Trevor L.;Adams, Megan A.;Cullen, J. Michael;Pomfret, Elizabeth A.;Moore, Hunter B.
• 通讯作者: Moore, Hunter B.

MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.

• DOI: 10.1002/rth2.12669
• 发表时间: 2022-03
• 期刊: Research and practice in thrombosis and haemostasis
• 影响因子: 4.6
• 作者: Barrett CD;Moore HB;Moore EE;Benjamin Christie D 3rd;Orfanos S;Anez-Bustillos L;Jhunjhunwala R;Hussain S;Shaefi S;Wang J;Hajizadeh N;Baedorf-Kassis EN;Al-Shammaa A;Capers K;Banner-Goodspeed V;Wright FL;Bull T;Moore PK;Nemec H;Thomas Buchanan J;Nonnemacher C;Rajcooar N;Ramdeo R;Yacoub M;Guevara A;Espinal A;Hattar L;Moraco A;McIntyre R;Talmor DS;Sauaia A;Yaffe MB
• 通讯作者: Yaffe MB