Diversity Supplement to R35 - Mechanistic Elucidation and Targeted Therapy of Organ Injury and Inflammation following Trauma

R35 的多样性补充 - 创伤后器官损伤和炎症的机制阐明和靶向治疗

• 批准号: 10627526
• 负责人: Matthew D Neal
• 金额: $ 9.91万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627526
• 关键词: Achievement; Acute Lung Injury; Address; Age-Years; Agonist; Air; Amaze; Apoptosis; Appointment; Area; Attenuated; Automobile Driving; Award; Biochemical; Biology; Blood Platelets; Blood Transfusion; Blood Vessels; Blood coagulation; Caring; Cause of Death; Cessation of life; Chemotaxis; Chemotherapy-Oncologic Procedure; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Collaborations; Critical Illness; Data Analyses; Defect; Development; Development Plans; Disease; Doctor of Philosophy; Drug Delivery Systems; Drug Targeting; Endothelial Cells; Endothelium; Event; Faculty; Fibrin; Fostering; Functional disorder; Funding; Gender; Goals; HMGB1 Protein; Hemorrhage; Hemostatic function; Hispanic; Hospitals; Hydroxychloroquine; Immune; Immune system; Immunomodulators; Individual; Inferior vena cava structure; Inflammasome; Inflammation; Inflammatory; Injury; Innate Immune Response; Interleukin-1 beta; Journals; Kidney; Knowledge; Laboratories; Lead; Ligation; Link; Liposomes; Lung; Malignant neoplasm of pancreas; Manuscripts; Mediator of activation protein; Medical; Medical center; Medicine; Mentors; Mentorship; Microfluidics; Modernization; Molecular; Morbidity - disease rate; Multiple Organ Failure; Nanotechnology; Needles; Neoadjuvant Therapy; Neutrophil Activation; Neutrophil Infiltration; New England; Oncology; Operative Surgical Procedures; Organ; Outcome; Pathogenesis; Pathology; Patients; Pattern; Phase; Physicians; Plasma; Platelet Activation; Platelet Count measurement; Positioning Attribute; Prevention; Process; Production; Program Development; Prospective cohort study; Proteins; Publications; Publishing; Randomized Controlled Trials; Regulation; Research; Research Assistant; Resuscitation; Risk; Risk Factors; Role; Sampling Studies; Science; Scientist; Secure; Sepsis; Signaling Protein; Survivors; System; TLR4 gene; Teacher Professional Development; Techniques; Testing; Therapeutic; Thrombocytopenia; Thrombosis; Thrombus; Time; Tranexamic Acid; Trauma; Trauma Research; Trauma patient; Underrepresented Populations; Universities; Vascular Diseases; Venous; Whole Blood; Work; base; career development; clinical application; clinical investigation; design; disability; diversity and inclusion; exosome; experience; experimental study; extracellular; extracellular vesicles; human disease; immune activation; immunothrombosis; improved; innovation; insight; intravital microscopy; lung injury; member; monocyte; mortality; mouse model; nanoparticle; neutrophil; novel; novel therapeutics; organ injury; parent grant; platelet function; post intervention; post-trauma; preventable death; professor; programs; receptor; receptor for advanced glycation endproducts; research and development; response; single-cell RNA sequencing; success; targeted treatment; thromboinflammation; thrombotic; thrombotic complications; translational research program; translational study; trauma induced coagulopathy

Project Summary/Abstract from the Parent Grant (R35 to Matthew Neal): Multiple organ dysfunction syndrome (MODS) is a leading cause of death after severe trauma, which is a leading cause of mortality worldwide. MODS is thought to be a consequence of a vicious cascade of excessive inflammation and coagulation abnormalities but remains incompletely understood. The overarching goal of our research is to understand how trauma leads to organ injury through inflammation and clotting of blood vessels, or immunothrombosis. Our research focus is the central role of platelet function in driving immunothrombosis after trauma. We propose to tackle the following key knowledge gaps in the field: 1) Understand the cellular mechanisms leading to micro-thrombotic organ injury in survivors after trauma 2) Unravel the immune and inflammatory consequences of modern trauma resuscitation 3) Design targeted interventions for post-traumatic organ injury and thrombosis Project Summary/Abstract for the Diversity Research Supplement: The career development focus of this diversity research supplement is to foster the continuous effort of inclusion of faculty from under represented groups by increasing diversity in the Department of Surgery at the University of Pittsburgh and the University of Pittsburgh Medical Center. Dr. Mota Alvidrez as a Hispanic junior faculty member is a perfect candidate for this supplement as a very promising physician scientist that brings his expertise to this research team. His inclusion as a diverse individual will also focus in developing further his expertise in platelet biology/function, immunothrombosis and endothelial damage using state of the art microfluidic system assessment. Inclusion of Dr. Mota Alvidrez as faculty in our department aims to foster the success of the project but also by increasing diversity in faculty appointments particularly by the addition of highly determined and strong-driven individuals as Dr. Mota Alvidrez. The research supplement aims to develop Dr. Mota Alvidrez independent research program by growing the mechanisms outlined in the parent grant with his own independent research development plan. He has an amazing mentoring team with an outlined 5-year plan that will allow ample time for faculty development, data analysis, mentoring and grantsmanship for him to secure independent funding to build his research program and laboratory. The proposed research supplement for Dr. Mota Alvidrez will focus on expanding the scope of the key challenges in the parent grant outlined above. The scientific scope will add novel hypothesis-driven experimental studies from the exciting preliminary plan from Dr. Mota Alvidrez to promote the development of his independent research program focusing in immunothrombosis. Dr. Mota Alvidrez research will fill knowledge gaps in the field of immunothrombosis in trauma while advancing the needle in post-injury care. He proposes to study deeper into the endothelial damage post trauma by evidencing platelet receptor shedding, particularly GPIb, leading to thrombocytopenia. His work will evaluate how dysfunctional platelets leads to platelet sequestration and microthrombi formation by evaluating the A2 domain in von Willbrand factor as a key mediator of multimer formation in this process.

项目摘要/家长资助摘要（R35 给 Matthew Neal）：多器官功能障碍 综合征（MODS）是严重创伤后死亡的主要原因，是导致死亡的主要原因 全世界。 MODS 被认为是过度炎症和恶性连锁反应的结果。 凝血异常，但仍不完全清楚。我们研究的总体目标是 了解创伤如何通过炎症和血管凝血导致器官损伤，或 免疫血栓形成。我们的研究重点是血小板功能在驱动免疫血栓形成中的核心作用 外伤后。我们建议解决该领域的以下关键知识差距： 1）了解导致创伤后幸存者微血栓性器官损伤的细胞机制 2) 揭示现代创伤复苏的免疫和炎症后果 3）设计针对创伤后器官损伤和血栓形成的针对性干预措施 多样性研究增刊的项目摘要/摘要：该项目的职业发展重点 多样性研究补充是为了促进不断努力纳入代表性不足的教师 通过增加匹兹堡大学和匹兹堡大学外科系的多样性来群体 匹兹堡医疗中心。 Mota Alvidrez 博士作为一名西班牙裔初级教员，是以下职位的完美人选： 作为一位非常有前途的医学科学家，他将他的专业知识带到了这个研究团队中。他的 作为一个多元化的个体，包容性还将专注于进一步发展他在血小板生物学/功能方面的专业知识， 使用最先进的微流体系统评估免疫血栓形成和内皮损伤。包容性 Mota Alvidrez 博士作为我们系的教员，旨在促进该项目的成功，但也 增加教师任命的多样性，特别是通过增加高度坚定和强烈的驱动力 Mota Alvidrez 博士等个人。该研究增刊旨在培养 Mota Alvidrez 博士的独立性 通过利用他自己的独立研究来发展家长补助金中概述的机制的研究计划 发展计划。他拥有一支出色的指导团队，并制定了五年计划，将提供充足的时间 为他提供教师发展、数据分析、指导和资助，以确保获得独立资金 建立他的研究计划和实验室。 Mota Alvidrez 博士拟议的研究补充将侧重于扩大关键范围 上述家长补助金中的挑战。科学范围将增加新的假设驱动 Mota Alvidrez 博士令人兴奋的初步计划的实验研究，旨在促进 他的独立研究项目专注于免疫血栓形成。 Mota Alvidrez 博士的研究将填补 创伤免疫血栓形成领域的知识差距，同时推进损伤后护理的针头。 他建议通过证实血小板受体来更深入地研究创伤后内皮损伤 脱落，尤其是 GPIb，导致血小板减少症。他的工作将评估功能失调的血小板如何 通过评估 von Willbrand 中的 A2 结构域导致血小板隔离和微血栓形成 因子作为该过程中多聚体形成的关键介质。