Platelet-Leukocyte Interactions in Sepsis

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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.