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
Slaughter, Anne L; D'Alessandro, Angelo; Moore, Ernest E et al. (2016) Glutamine metabolism drives succinate accumulation in plasma and the lung during hemorrhagic shock. J Trauma Acute Care Surg 81:1012-1019
D'Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E et al. (2016) Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock. Shock 46:173-82
Kelher, Marguerite R; McLaughlin, Nathan J D; Banerjee, Anirban et al. (2016) LysoPCs induce Hck- and PKCδ-mediated activation of PKCγ causing p47phox phosphorylation and membrane translocation in neutrophils. J Leukoc Biol :
Moore, Hunter B; Moore, Ernest E; Burlew, Clay C et al. (2016) Establishing Benchmarks for Resuscitation of Traumatic Circulatory Arrest: Success-to-Rescue and Survival among 1,708 Patients. J Am Coll Surg 223:42-50
Moore, Hunter B; Moore, Ernest E; Liras, Ioannis N et al. (2016) Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients. J Am Coll Surg 222:347-55
Chapman, Michael P; Moore, Ernest E; Moore, Hunter B et al. (2016) Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. J Trauma Acute Care Surg 80:16-23; discussion 23-5
D'alessandro, Angelo; Nemkov, Travis; Moore, Hunter B et al. (2016) Metabolomics of trauma-associated death: shared and fluid-specific features of human plasma vs lymph. Blood Transfus 14:185-94
Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C (2015) Three-minute method for amino acid analysis by UHPLC and high-resolution quadrupole orbitrap mass spectrometry. Amino Acids 47:2345-57
Chapman, Michael P; Moore, Ernest E; Chin, Theresa L et al. (2015) Combat: Initial Experience with a Randomized Clinical Trial of Plasma-Based Resuscitation in the Field for Traumatic Hemorrhagic Shock. Shock 44 Suppl 1:63-70
D'Alessandro, Angelo; Nemkov, Travis; Kelher, Marguerite et al. (2015) Routine storage of red blood cell (RBC) units in additive solution-3: a comprehensive investigation of the RBC metabolome. Transfusion 55:1155-68

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