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Endothelial Glycocalyx Disintegrity: Repairing the Damage caused by Trauma-Hemorrhage

Award Number: R35GM137958
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Endothelial Glycocalyx Disintegrity: Repairing the Damage caused by Trauma-Hemorrhage - PROJECT SUMMARY/ABSTRACT The aim of this R35 application is to develop a high quality, translational research program in inflammation- induced endothelial damage and organ dysfunction. Dysregulation of microvascular function contributes to the pathophysiology of indirect organ injury after trauma. In particular, damage to the endothelial glycocalyx occurs within minutes of traumatic injury and is associated with increased microvascular permeability resulting in multi- organ failure and increased mortality. Strategies that attenuate glycocalyx disintegrity by preventing its cleavage and/or facilitating its repair hold significant promise for minimizing microvascular dysfunction and post-traumatic organ injury. The long-term objective of our research program is to establish basic science and translational studies that focus on the identification of novel therapeutic targets that will (1) prevent glycocalyx damage, (2) repair glycocalyx integrity or (3) inhibit dysregulation of endothelial cell permeability that occurs as a result of glycocalyx disintegrity. The specific programmatic areas of focus will include studies to identify the role of heparanase in regulating glycocalyx (dis)integrity after trauma-hemorrhage and on mechanisms that mediate glycocalyx synthesis. Additionally, our proposed studies will identify signaling pathways that regulate endothelial barrier function that are effected by loss of cell surface glycosaminoglycans, heparan sulfate and hyaluronic acid, which are primary constituents of the glycocalyx layer. Our research program will focus on the endothelial cell- specific response to trauma-hemorrhage in organ systems that are most susceptible to secondary injury (e.g., kidney, lung and intestines) with the over-arching goal of determining how resuscitation strategies mediate glycocalyx-dependent mechanisms in each organ. These programmatic areas of research hold promise for significantly impacting the current resuscitation paradigm for patients in hemorrhagic shock by aiding in the discovery of novel therapeutic targets that can be used to inhibit glycocalyx dysfunction, facilitate its repair or reverse the downstream consequences of glycocalyx disintegrity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $365,915 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	5	6/5/2024	NON-COMPETING CONTINUATION	$365,915
														Subtotal = $365,915

Issue Date FY: 2023 ( Subtotal = $615,903 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	001	4	6/27/2023	SUPPLEMENT FOR EXPANSION	$249,988
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	4	6/9/2023	NON-COMPETING CONTINUATION	$365,915
														Subtotal = $615,903

Issue Date FY: 2022 ( Subtotal = $365,915 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	3	6/13/2022	NON-COMPETING CONTINUATION	$365,915
														Subtotal = $365,915

Issue Date FY: 2021 ( Subtotal = $365,915 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	2	6/15/2021	NON-COMPETING CONTINUATION	$365,915
														Subtotal = $365,915

Issue Date FY: 2020 ( Subtotal = $340,101 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	1	8/27/2020	NEW	$340,101
														Subtotal = $340,101

Grand Total All Awards = $2,053,749

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Endothelial Glycocalyx Disintegrity: Repairing the Damage caused by Trauma-Hemorrhage

Award Number: R35GM137958

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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