Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMED CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to (I) hemorrhagic shock, (II), transfusion (III), mechanisms of anti-inflammatory resuscitation. The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project. I focuses on lung injury induced by the cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to eicosanoid metabolism. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and dissect its components. Project. II undertakes a detailed analysis of lipids and proteins accruing in blood products, focusing on the acute coagulopathy of trauma with the aim of minimizing mortality by proper blood resuscitation. Project. Ill examines mechanism of reducing inflammation by regulating transcription factor activation with hypertonic solution and seeks to apply inhaled hypertonic saline to reduce lung inflammation in animals and humans. To validate these ideas, the Human Core is charged with supplying specimens, gathering data, and updating the Trauma MOF database while remaining in strict regulatory compliance. A vigorous Cell, Imaging &Proteomics Core will provide each project with commonly used human cells, equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies as well and advanced MS proteomics . These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions (Denver Health Medical Center, Belle Bonfils Blood Center, University of Colorado Health Sciences Center) to promulgate Trauma Research and improve patient care.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM049222-19
Application #
8499325
Study Section
Special Emphasis Panel (ZGM1-PPBC-5 (TR))
Program Officer
Somers, Scott D
Project Start
1997-04-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
19
Fiscal Year
2013
Total Cost
$2,057,405
Indirect Cost
$665,558
Name
University of Colorado Denver
Department
Surgery
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Coleman, Julia R; Moore, Ernest E; Chapman, Michael P et al. (2018) Rapid TEG efficiently guides hemostatic resuscitation in trauma patients. Surgery 164:489-493
Banerjee, Anirban; Silliman, Christopher C; Moore, Ernest E et al. (2018) Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma. J Trauma Acute Care Surg 84:929-938
Moore, Ernest E; Moore, Hunter B; Chapman, Michael P et al. (2018) Goal-directed hemostatic resuscitation for trauma induced coagulopathy: Maintaining homeostasis. J Trauma Acute Care Surg 84:S35-S40
Reisz, Julie A; Wither, Matthew J; Moore, Ernest E et al. (2018) All animals are equal but some animals are more equal than others: Plasma lactate and succinate in hemorrhagic shock-A comparison in rodents, swine, nonhuman primates, and injured patients. J Trauma Acute Care Surg 84:537-541
Stettler, Gregory R; Moore, Ernest E; Nunns, Geoffrey R et al. (2018) Rotational thromboelastometry thresholds for patients at risk for massive transfusion. J Surg Res 228:154-159
Nunns, Geoffrey R; Stringham, John R; Gamboni, Fabia et al. (2018) Trauma and hemorrhagic shock activate molecular association of 5-lipoxygenase and 5-lipoxygenase-Activating protein in lung tissue. J Surg Res 229:262-270
Moore, Hunter B; Moore, Ernest E; Chapman, Michael P et al. (2018) Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet 392:283-291
Kuldanek, Susan; Silliman, Christopher C (2018) Mortality after red blood cell transfusions from previously pregnant donors: complexities in the interpretation of large data. J Thorac Dis 10:648-652
Nunns, Geoffrey R; Moore, Ernest E; Stettler, Gregory R et al. (2018) Empiric transfusion strategies during life-threatening hemorrhage. Surgery 164:306-311
Slaughter, Anne L; Nunns, Geoffrey R; D'Alessandro, Angelo et al. (2018) The Metabolopathy of Tissue Injury, Hemorrhagic Shock, and Resuscitation in a Rat Model. Shock 49:580-590

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