Platelet-Leukocyte Interactions in Sepsis

脓毒症中血小板与白细胞的相互作用

• 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
• 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

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.

这是修订后的NHLBI K24应用程序，用于Matthew Rondina博士的中期职业生涯研究者奖， 导向研究。在犹他州大学，Rondina博士是受资助的NHLBI R 01和VA的联系PI Merit Award支持败血症患者的纵向招募，以及血小板分离，临床数据 收集和结果分析。他指导了来自不同领域的大量且不断增长的临床研究人员 学科Rondina博士的总体目标是：1）提高他作为导师的技能，从而为更多的人服务 有效地作为一个榜样，并指导，初级研究人员致力于以病人为导向的研究; 2） 确定脓毒症如何上调血小板上MHCI的抗原呈递，从而促进CD 8 + T细胞 细胞抑制和免疫功能障碍; 3）专注于精心挑选的职业发展 活动，以增加他的T细胞生物学和免疫学的知识-提高他的能力，指导临床 学员在这方面。该应用程序描述了职业发展，指导和研究活动， 将在未来五年内执行，受NHLBI K24裁决的保护时间。Rondina医生 学员将学习和应用创新技术来研究败血症患者的血小板和白细胞， 适当的对照参与者，并确定败血症中的血小板/白细胞变化是否与 临床结果。这个以患者为导向的研究项目将作为Rondina博士扩展的平台 他的导师为学员从事以病人为导向的研究， 独立的职业。Rondina博士将在本项目期间从事职业发展活动， 包括1）提高他对初级临床研究人员的指导技能，包括代表性不足的少数民族， 以及2）扩展他的免疫学和CD 8 + T细胞生物学知识。这些活动将扩大博士。 Rondina的指导能力，有效性和在五年奖励期内的影响力。他有足够的权限 通过他与VPCAT和分子医学项目、犹他州StARR项目的合作， 以及犹他州CTSA KL 2和TL 1计划。此外，Rondina博士将与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，肺部和重症监护、血液学， 传染病），与学生在犹他州医学博士和医学博士/博士课程，并与初级 传统上代表性不足的背景的调查人员。K24奖将使Rondina博士能够 显著扩大他的积极指导作用和以病人为导向的研究，并将导致培训 下一代生物医学科学家