The sole specific aim of the training described in this proposal is to provide postdoctoral fellows with state-of-the-art research training in the basic biologic sciences which are relevant to unsolved problems in the fields of trauma and sepsis. Our primary goal is to train clinicians, usually surgeons, to reduce clinical problems in trauma and sepsis into their essential biological components -- the biological questions can then be addressed by sustained and imaginative laboratory investigation. By and large, these biological questions are so complex that coordinate and sophisticated approaches in immunology, cell biology, biochemistry, molecular biology, and computational/systems biology are necessary. Trauma, both accidental and surgical, induces a complex multifaceted response, much of which is the result of the induction of an array of inflammatory and anti-inflammatory mediators (e.g., cytokines, chemokines, and reactive radicals), which in turn regulate biochemical and genetic responses (e.g., autophagy, apoptosis, necroptosis). Similarly, sepsis evokes primitive, highly conserved innate inflammatory pathways which are usually protective, but when excessive, can be detrimental to recovery and survival. These responses ultimately lead to the physiologic changes seen as clinical phenomena (e.g., organ dysfunction). The time has long passed when detailed physiologic monitoring and empiric solutions will suffice. We have entered the era of large-scale genomic, proteomic, and physiomic analysis. It is likely that these approaches, coupled with multi-scale computational analysis as well as the more traditional focused molecular analysis, will be needed to address the complex questions in trauma and sepsis research and guide us to novel therapies. The focus of this proposal is to provide the trainees with the tools to develop relevant hypotheses and then apply state-of-the-art approaches to these questions. Innate immunity, cell signaling, and systems biology have been and remain the areas of focused research in our program.
Trauma is the most common cause of death and morbidity for people under the age of 54 years. Progress in reducing the death rate and serious complications that occur after injury requires individuals trained not only in the clinical care of surgical patients, but also the fundamentals of basic research. This training program is designed to prepare surgeons to identify the appropriate research questions and equip these clinician-investigators with the skills needed to provide the answers for the benefit of trauma patients.
|Dyer, Mitchell R; Chen, Qiwei; Haldeman, Shannon et al. (2018) Deep vein thrombosis in mice is regulated by platelet HMGB1 through release of neutrophil-extracellular traps and DNA. Sci Rep 8:2068|
|Lewis, Anthony J; Griepentrog, John E; Zhang, Xianghong et al. (2018) Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial. Crit Care Med 46:e426-e434|
|Lewis, Anthony J; Zhang, Xianghong; Griepentrog, John E et al. (2018) Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis. Crit Care Med 46:e779-e787|
|Brown, Joshua B; Gestring, Mark L; Leeper, Christine M et al. (2018) Characterizing injury severity in nonaccidental trauma: Does Injury Severity Score miss the mark? J Trauma Acute Care Surg 85:668-673|
|Brown, Joshua B; Rosengart, Matthew R; Billiar, Timothy R et al. (2017) Distance matters: Effect of geographic trauma system resource organization on fatal motor vehicle collisions. J Trauma Acute Care Surg 83:111-118|
|Shukla, M; Sekhon, U D S; Betapudi, V et al. (2017) In vitro characterization of SynthoPlate™ (synthetic platelet) technology and its in vivo evaluation in severely thrombocytopenic mice. J Thromb Haemost 15:375-387|
|Zhang, Xianghong; Yuan, Du; Sun, Qian et al. (2017) Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis. FASEB J 31:4382-4395|
|Brown, Joshua B; Gestring, Mark L; Leeper, Christine M et al. (2017) The value of the injury severity score in pediatric trauma: Time for a new definition of severe injury? J Trauma Acute Care Surg 82:995-1001|
|Brown, Joshua B; Gestring, Mark L; Guyette, Francis X et al. (2017) External validation of the Air Medical Prehospital Triage score for identifying trauma patients likely to benefit from scene helicopter transport. J Trauma Acute Care Surg 82:270-279|
|Zettel, Kent R; Dyer, Mitchell; Raval, Jay S et al. (2017) Aged Human Stored Red Blood Cell Supernatant Inhibits Macrophage Phagocytosis in an HMGB1 Dependent Manner After Trauma in a Murine Model. Shock 47:217-224|
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