Endothelial dysfunction and restoration in trauma induced coagulopathy
Active Project Grant Awarded Last action
- Award ID
- R01HL166944
- Recipient
-
University Of Pittsburgh - Of The Commonwealth System Of Higher Education UEI MKAGLD59JRL1
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $7,179,267
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 64% complete
- Place of performance
- Pittsburgh, PA 15222, USA
Award details come from USAspending.gov.
Description
- Abstract
- Trauma-induced coagulopathy (TIC) is a leading driver of morbidity and mortality following severe injury. Affecting as many as 30% of critically ILL trauma patients, TIC represents a spectrum of coagulation phenotypes ranging from early impaired hemostasis to later micro and macrovascular thrombotic complications. We have identified that patients with TIC have evidence of severe endothelial damage, and these markers of endothelial injury correlate closely with outcomes in trauma. Further, through randomized controlled trials testing pre- hospital plasma as a resuscitation tool, we have identified that plasma transfusion can reduce endothelial injury, even in the patients with the highest injury severity. Plasma transfusion reduces mortality after severe trauma, but the exact mechanism of benefit is unknown. In the present proposal, we address the central hypothesis that the endothelium is a central regulator of TIC. We propose to characterize the role of the endothelium as the regulator of maladaptive response and a crucial interface for thrombosis-inflammation crosstalk. Our strategy will focus on identifying key circulating mediators after trauma that induce endothelial injury. We will utilize a "CUE, signal, response" framework to robustly characterize the molecular pathways activated in the endothelial and how the endothelial response interfaces with changes in the coagulation response. Finally, we will define the "reparative phenotype" that plasma transfusion creates, restoring the endothelium to homeostasis. We will use this to test targeted therapies to address the unmet needs in trauma resuscitation targeting endothelial health. The approach will leverage state-of-the-science and novel techniques in proteomics, transcriptomics, metabolomics, advanced microvascular imaging, and pre-clinical models of trauma and hemorrhage in addition to a large repository of previously collected trauma patient samples.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $2,365,012 | |
| Amendment | $2,334,771 | |
| Original award | $2,479,484 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of Vermont & State Agricultural College | $1,122,141 | |
| Scripps Research Institute | $985,326 | |
| Regents Of The University Of Michigan | $1,180,730 | |
| The Regents Of The University Of California. San Francisco | $411,079 | |
| Massachusetts Institute Of Technology | $480,095 | |
| The Regents Of The University Of California. San Francisco | $108,499 | |
| University Of Vermont & State Agricultural College | $347,957 | |
| The Regents Of The University Of Colorado | $448,504 |
Quick answers
Who received award R01HL166944?
R01HL166944 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by National Heart Lung and Blood Institute (National Institutes of Health) on September 15, 2023.
How much is award R01HL166944 worth?
$7,179,267 has been obligated on R01HL166944.
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