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Research |
NIH T32 Research Training |
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Host Response to Trauma Research Training ProgramTraumatic injury is the leading cause of death in the United States in individuals under the age of 44 years. More than 100,000 deaths each year in the United States alone are attributed to trauma. With the advent of new technologies and strategies to resuscitate, stabilize, and transport trauma patients, individuals are now surviving insults that in years past would have been lethal. This sets the stage for an often prolonged series of complications that may subsequently lead to death for reasons other than the original traumatic injury. A greater understanding of the biological mechanisms of traumatic injury and its complications may lead to the development of new diagnostics, treatment modalities and patient care practices. Our trauma training program is designed to directly investigate those mechanisms. Our program is unique in that it involves numerous clinicians and scientists from multiple departments that offer a tremendous breadth of expertise and perspective. Trainees devote 2-3 years to conduct research on a topic related to trauma, burns or perioperative injury. In addition, didactic training is provided in the responsible conduct of research and research ethics and additional topics as necessary. The training program is entering its 18th year and to date has trained over 30 individuals, many of which have gone on to successful academic careers. Program Faculty Current Trainees
During sepsis, exquisite control of inflammation is necessary to execute beneficial actions (bacterial clearance) while minimizing pathogenesis. Initially, activated leukocytes participate in the anti-microbial response. During sepsis, leukocytes can undergo apoptosis or become unresponsive. In other inflammatory models, both activated and apoptotic leukocytes have been shown to be precursors to neutrophil-derived microparticles (NDMPs). NDMPs are small vesicles of heterogeneous density and composition. The role of MPs in sepsis is currently poorly characterized. Dr. Johnson will conduct research to determine signaling mechanisms driving NDMP formation and elucidate mechanisms of NDMP-associated macrophage de-activation during sepsis. Jillian Richter, Ph.D. Dr. Richter is investigating the mechanisms by which stored red blood cells generate microparticles. More specifically, she had developed a hypothesis that oxidative stress during the storage of RBCs results in activation of caspase-3 and remodeling of cytoskeletal and membrane components leading to the generation of microparticles. In addition, she is examining the hemostatic properties of RBC microparticles as a novel adjunct to hemorrhage resuscitation. For the latter, she will use a murine model of non-compressible hemorrhagic shock. After hemorrhage, resuscitation is required for survival and recovery. Recently, resuscitation strategy for hemorrhagic shock has undergone a major change, with emphasis on the early use of blood products, including stored packed red blood cell units. Studies from our and other laboratories have demonstrated that stored units of packed red blood cells are associated with increased harm to the recipient. Our preliminary data indicate that several changes that occur during the units during storage, including the formation of red blood cell microparticles, may be responsible for harmful effects of transfusion with stored packed red blood cells. Dr. Sutton will conduct research to determine the mechanisms by which red blood cell derived microparticles cause harm. Dr. Yang is investigating the local and systemic inflammatory response after mild traumatic brain injury (mTBI). He is in the final stages of characterizing and validating a murine model of closed head injury that replicates many aspects of mTBI in humans. He will be examining the roles of inflammatory mediators that are produced locally in the brain as well as systemically on cognitive and motor functions over time as well as their role in regulating inflammatory injury and susceptibility to secondary trauma such as hemorrhagic shock and sepsis. Additional Information/Application
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