BLRD Research Career Scientist Award Application

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PROJECT SUMMARY Jie Fan, M.D., M.Sc. has been working in the VA Pittsburgh Healthcare System (VAPHS) since 2003 and is a VA Research Career Scientist, a Director of the Surgical Research Program, a Vice- Chair of the Institutional Animal Care and Use Committee, a Mentor of VA Career Development Awardees at VAPHS, and a tenured Full Professor of Surgery and Immunology in the Departments of Surgery and Immunology at the University of Pittsburgh. He is a Principal Investigator working on the cellular and molecular mechanisms of post-trauma and post-sepsis systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI), an important but exceptionally difficult area. His laboratory has been continuously funded by VA merit review grants since 2007 and NIH research grants (R01, P50, and R56) since 2005. The burden of trauma- and sepsis-related diseases is considerable in veterans. Following exsanguination and/or brain injury that commonly result in early phase death, more than 60% of surviving patients later die of causes related to the development of SIRS, sepsis, and ALI. This patient population is well suited for prophylactic interventions aimed at preventing these occurrences because of the time lag before the onset of organ inflammation and failure. Nonetheless, few specific targets have been identified that predispose to SIRS and ALI. The long-term goal of Dr. Fan's studies is to provide a new understanding of the mechanisms of post-trauma/post-infection inflammation and organ dysfunction and to develop novel preventive and therapeutic interventions in SIRS, sepsis, and ALI. The studies by Dr. Fan's team will also provide a greater understanding of the pathogenesis of multiple human diseases in which inflammation plays a central role. ALI is one of the common endpoints of SIRS and sepsis. SIRS and sepsis are common causes of mortality following surgery, infection, spinal injury, stroke, hemorrhage, and trauma in the veteran population. And thus, Dr. Fan's research is highly relevant to veterans' health. Dr. Fan is a highly productive Principal Investigator with a long track record of both VA and NIH funding. He has also served in roles such as Co-Investigator, Consultant, and Collaborator on numerous other's research grants. His research and collaborations have resulted in 136 peer-reviewed publications, many of them in the first-line scientific journals, including Nature Medicine, Nature Communications, Journal of Clinical Investigation, Hepatology, Journal of Hepatology, Cell Death & Differentiation, and Journal of Immunology. Dr. Fan's work is renowned by his peers nationally and internationally. He has been an invited speaker at numerous national and international conferences and at many research and educational institutions. He serves as a regular or Ad Hoc member in a number of national peer-review committees, including NIH, VA, DoD, American Institution of Biological Sciences study sections, and European scientific institutions. He also serves as an editor-in-chief, member of editorial board, and invited reviewer for over 50 scientific journals. He has mentored 33 VA and VA WOC trainees including VA Career Development Awardee, surgery residents, Ph.D. candidates, postdoctoral fellows, and visiting scholars, many of whom have now become independent scientists or physician-scientists.