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.

Public Health Relevance

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.

National Institute of Health (NIH)
Institutional National Research Service Award (T32)
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Special Emphasis Panel (ZGM1)
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Somers, Scott D
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University of Pittsburgh
Schools of Medicine
United States
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Brown, Joshua B; Cohen, Mitchell J; Minei, Joseph P et al. (2015) Pretrauma center red blood cell transfusion is associated with reduced mortality and coagulopathy in severely injured patients with blunt trauma. Ann Surg 261:997-1005
Brown, Joshua B; Forsythe, Raquel M; Stassen, Nicole A et al. (2014) Evidence-based improvement of the National Trauma Triage Protocol: The Glasgow Coma Scale versus Glasgow Coma Scale motor subscale. J Trauma Acute Care Surg 77:95-102; discussion 101-2
Howell, Gina M; Gomez, Hernando; Collage, Richard D et al. (2013) Augmenting autophagy to treat acute kidney injury during endotoxemia in mice. PLoS One 8:e69520
Li, Hui; Rodriguez, Janel; Yoo, Youngdong et al. (2011) Cooperative and antagonistic contributions of two heterochromatin proteins to transcriptional regulation of the Drosophila sex determination decision. PLoS Genet 7:e1002122
McCloskey, Carol A; Kameneva, Marina V; Uryash, Arkady et al. (2004) Tissue hypoxia activates JNK in the liver during hemorrhagic shock. Shock 22:380-6
McCloskey, Carol A; Zuckerbraun, Brian S; Gallo, David J et al. (2003) A role for angiotensin II in the activation of extracellular signal-regulated kinases in the liver during hemorrhagic shock. Shock 20:316-9
Chen, L C; Kepka-Lenhart, D; Wright, T M et al. (1999) Salicylate-enhanced activation of transcription factors induced by interferon-gamma. Biochem J 342 Pt 3:503-7
Morris Jr, S M; Kepka-Lenhart, D; Chen, L C (1998) Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells. Am J Physiol 275:E740-7