Platelet-Leukocyte Interactions in Sepsis

脓毒症中血小板与白细胞的相互作用

基本信息

批准号：
10676877
负责人：
Matthew Thomas Rondina
金额：
$ 12.12万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10676877
关键词：
Agonist Antigen Presentation Antigen Presentation Pathway Antigen-Presenting Cells Antigens Apoptosis Area Award Bioinformatics Biological Blood Platelets CD8-Positive T-Lymphocytes Cardiovascular Diseases Cell Count Cell physiology Cells Cellular biology Cessation of life Clinical Clinical Data Clinical Investigator Clinical Research Communicable Diseases Critical Care Data Data Collection Discipline Doctor of Philosophy Effectiveness Effector Cell Event Fellowship Funding Gene Expression Grant Hematology Human Immune System Diseases Immunity Immunology Immunosuppression Impairment Inflammatory Knowledge Learning Leukocytes Lung Major Histocompatibility Complex Malignant Neoplasms Mediating Megakaryocytes Mentors Mentorship Methods Mid-Career Clinical Scientist Award (K24)Midcareer Investigator Award in Patient-Oriented Research Molecular Molecular Medicine Morbidity - disease rate National Heart, Lung, and Blood Institute Outcome Participant Pathogenicity Patients Peptides Phenotype Process Proteins Proteome Publishing RNA Research Research Activity Research Personnel Research Project Grants Risk Role Sample Size Sampling Secondary to Sentinel Sepsis Students Supervision Survivors Syndrome T-Lymphocyte TNFSF15 gene Techniques Testing Time Tissue-Specific Gene Expression Training Underrepresented Minority Universities Up-Regulation Utah Work adverse outcome biomedical scientist career career development cohort cytokine design gene function genome editing improved innovation innovative technologies monocyte mortality next generation novel novel therapeutic intervention patient oriented research platelet function programs recruit response role model secondary infection septic septic patients skills tool transcriptome transcriptome sequencing

项目摘要

This is a revised NHLBI K24 application for Dr. Matthew Rondina’s Midcareer Investigator Award in Patient- Oriented Research. At the University of Utah, Dr. Rondina is the contact PI for a funded NHLBI R01 and VA Merit Award supporting the longitudinal recruitment of sepsis patients, as well as platelet isolation, clinical data collection, and outcomes analyses. He mentors a large and growing cadre of clinical investigators from diverse disciplines. Dr. Rondina’s overall aims are to 1) improve his skills as a mentor and therefore serve more effectively as a role model for, and mentor to, junior investigators devoted to patient-oriented research; 2) determine how sepsis upregulates antigen presentation by MHCI on platelets, thereby contributing to CD8+ T cell suppression and immune dysfunction; and 3) engage in focused and carefully selected career development activities to increase his knowledge of T cell biology and immunology – improving his ability to mentor clinical trainees in this area. This application describes career development, mentoring, and research activities that would be executed in the next five years under protected time afforded by this NHLBI K24 award. Dr. Rondina’s mentees will learn and apply innovative technologies to study platelets and leukocytes in sepsis patients and appropriate control participants, and to determine if platelet/leukocyte changes in sepsis are associated with clinical outcomes. This patient-oriented research project will serve as a platform for Dr. Rondina to expand his mentorship for trainees to engage in patient-oriented research on their path towards successful, independent careers. Dr. Rondina will engage in career development activities during this project period, including 1) improving his mentoring skills for junior clinician investigators, including underrepresented minorities, and 2) expanding his knowledge of immunology and CD8+ T cell biology. These activities will expand Dr. Rondina’s mentoring capacity, effectiveness, and reach over the five-year award period. He has ample access to mentees through his work with the VPCAT and Molecular Medicine Programs, the Utah StARR Program, and the Utah CTSA KL2 and TL1 Programs. In addition, Dr. Rondina will interface with clinical fellows in subspecialty fellowships pertinent to the research proposed (e.g. Pulmonary and Critical Care, Hematology, Infectious Disease), with students in the University of Utah MD and MD/PhD Programs, and with junior investigators from traditionally underrepresented backgrounds. The K24 award will enable Dr. Rondina to significantly expand his active mentoring roles and patient-oriented research and will lead to the training of the next-generation of biomedical scientists.

这是 Matthew Rondina 博士在患者领域的职业生涯中期调查员奖的修订版 NHLBI K24 申请 - 在犹他大学，Rondina 博士是受资助的 NHLBI R01 和 VA 的联系人 PI。优异奖支持脓毒症患者的纵向招募以及血小板分离、临床数据他指导着一大批来自不同领域且不断壮大的临床研究人员。 Rondina 博士的总体目标是 1) 提高他作为导师的技能，从而为更多人服务。 2) 有效地成为致力于以患者为中心的研究的初级研究者的榜样和导师；确定脓毒症如何通过 MHCI 上调血小板上的抗原呈递，从而促进 CD8+ T 细胞抑制和免疫功能障碍；3）专注且精心选择的职业发展增加 T 细胞生物学和免疫学知识的活动 – 提高指导临床的能力该应用程序描述了该领域的受训者的职业发展、指导和研究活动。将在未来五年内在 NHLBI K24 奖项提供的保护时间内执行。学员将学习并应用创新技术来研究脓毒症患者的血小板和白细胞，适当的对照参与者，并确定脓毒症中血小板/白细胞的变化是否与这个以患者为导向的研究项目将作为 Rondina 博士扩展的平台。他指导学员在走向成功的道路上进行以患者为导向的研究， Rondina 博士将在该项目期间从事职业发展活动，包括 1) 提高对初级临床医生研究人员（包括代表性不足的少数群体）的指导技能， 2) 扩展他的免疫学和 CD8+ T 细胞生物学知识。这些活动将扩展 Dr. 朗迪纳在五年奖励期内的指导能力、有效性和影响力他有足够的机会。通过他在 VPCAT 和分子医学项目、犹他州 StARR 项目的工作，向受训者提供帮助，此外，Rondina 博士还将与犹他州 CTSA KL2 和 TL1 项目的临床研究员进行交流。与拟议研究相关的亚专业奖学金（例如肺科和重症监护、血液学、传染病），与犹他大学医学博士和医学博士/博士项目的学生以及大三学生一起来自传统上代表性不足的背景的研究人员将使 Rondina 博士能够显着扩大他的积极指导作用和以患者为导向的研究，并将导致培训下一代生物医学科学家。