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.

来自父母赠款的项目摘要/摘要（R35至Matthew Neal）：多个器官功能障碍 综合征（mods）是严重创伤后的主要死亡原因，这是死亡率的主要原因 全世界。国防部被认为是过度炎症的恶性级联的结果 凝血异常，但仍未完全理解。我们研究的总体目标是 了解创伤如何通过炎症和血管凝结或 免疫骨栓塞。我们的研究重点是血小板功能在驱动免疫骨骼中的核心作用 创伤后。我们建议解决该领域的以下关键知识差距： 1）了解创伤后幸存者导致幸存者微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目标干预措施 项目摘要/多样性研究补充：职业发展重点 多样性研究补充是为了促进不断纳入教师的努力 小组通过增加匹兹堡大学和大学手术系的多样性。 匹兹堡医疗中心。莫塔·阿尔维德雷斯（Mota Alvidrez）博士是西班牙裔初级教师 这种补充是一位非常有前途的医师科学家，将他的专业知识带给了这个研究团队。他的 将作为一个多元化的人都将集中在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的状态，免疫骨栓塞和内皮损伤。包容 Mota Alvidrez博士担任我们系的教师，旨在促进该项目的成功，但也是由 教师任命的多样性增加，特别是通过增加高度确定和强大的驱动 个人为Mota Alvidrez博士。研究补充旨在开发Mota Alvidrez博士独立 通过根据自己的独立研究提高父母赠款中概述的机制来研究计划 发展计划。他拥有一个出色的指导团队，其中有一个概述的5年计划，这将使时间充足 为教师开发，数据分析，指导和赠款技巧，以确保独立资金 建立他的研究计划和实验室。 拟议的Mota Alvidrez博士的研究补充将集中于扩大密钥的范围 上面概述的父母赠款中的挑战。科学范围将添加新颖的假设驱动 来自Mota Alvidrez博士的激动人心的初步计划的实验研究，以促进 他的独立研究计划着重于免疫栓塞。 Mota Alvidrez博士将填补 在伤害后护理中推进针刺的同时，在创伤中免疫栓塞领域的知识差距。 他建议通过证明血小板受体来深入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 通过评估Von Willbrand中的A2结构域，导致血小板隔离和微骨形成 在此过程中，因子是多聚体形成的关键调解人。