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
Lawson, Peter J; Moore, Hunter B; Moore, Ernest E et al. (2017) Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation. J Surg Res 220:171-175
Moore, Frederick A; Moore, Ernest E; Billiar, Timothy R et al. (2017) The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure. J Trauma Acute Care Surg 83:520-531
Stettler, Gregory R; Moore, Ernest E; Moore, Hunter B et al. (2017) Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion. Surgery 162:1286-1294
Moore, Hunter B; Moore, Ernest E; Chapman, Michael P et al. (2017) Viscoelastic Tissue Plasminogen Activator Challenge Predicts Massive Transfusion in 15 Minutes. J Am Coll Surg 225:138-147
Clendenen, Nathan; Nunns, Geoffrey R; Moore, Ernest E et al. (2017) Hemorrhagic shock and tissue injury drive distinct plasma metabolome derangements in swine. J Trauma Acute Care Surg 83:635-642
Sauaia, Angela; Moore, Frederick A; Moore, Ernest E (2017) Postinjury Inflammation and Organ Dysfunction. Crit Care Clin 33:167-191
Slaughter, Anne L; Nunns, Geoffrey R; D'Alessandro, Angelo et al. (2017) The Metabolopathy of Tissue Injury, Hemorrhagic Shock and Resuscitation in a Rat Model. Shock :
Silliman, Christopher C; Kelher, Marguerite R; Khan, Samina Y et al. (2017) Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation. Transfusion 57:2690-2700
Reisz, Julie A; Slaughter, Anne L; Culp-Hill, Rachel et al. (2017) Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats. Blood Adv 1:1296-1305
D?Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E et al. (2017) Plasma succinate is a predictor of mortality in critically injured patients. J Trauma Acute Care Surg 83:491-495

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