Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role of Hyaluronan-Mediated Signaling in Trauma-Induced Endotheliopathy

Award Number: F31HL184785
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

Group Awards By:

View Award Description

Role of Hyaluronan-Mediated Signaling in Trauma-Induced Endotheliopathy - PROJECT SUMMARY Hospitalized survivors of traumatic injury are at high risk of multi-organ dysfunction and poor clinical outcomes due to dysregulated immune responses and vascular endothelial damage. Understanding the mechanisms driving vascular endothelial damage and multi-organ dysfunction after trauma is crucial for developing therapeutic strategies that improve patient outcomes. The endothelial glycocalyx (eGCX), a mechanosensor that regulates vascular homeostasis, is disrupted following trauma. Hyaluronan (HA), a key glycosaminoglycan in the eGCX, regulates endothelial cell (EC) homeostasis through interactions with its receptor, CD44. Our previous work shows that trauma induces HA cleavage, and that trauma patients with coagulopathy and organ injury have elevated levels of circulating HA. However, the mechanistic consequences of HA cleavage on endothelial CD44 signaling that could promote endothelial dysfunction and poor clinical outcomes after trauma remains unclear. The proposed research aims to investigate whether trauma-induced eGCX damage disrupts HA-CD44 signaling, contributing to endothelial dysfunction and organ injury. We will also explore the role of toll-like receptor (TLR) signaling in mediating cellular responses to HA fragments based on the ability of low molecular weight HA to function as danger-associated molecular patterns (DAMPs). In Aim 1, we will use a mouse model of polytrauma and hemorrhagic shock (PT/HS) to explore the role of trauma-activated macrophages in causing HA fragmentation via release of enzymatically active hyaluronidases and the downstream implications of HA cleavage on CD44 signaling. We will validate the clinical relevance of these findings by analyzing plasma samples from trauma patients collected during our prior clinical studies. In Aim 2, we will explore the bioactivity of trauma-induced soluble HA fragments using an in vivo approach to assess the roles of CD44 and TLR4 signaling in HA-mediated vascular dysfunctions. Building on preliminary data that suggests shear stress regulates HA-mediated responses, we will employ an established EC flow model to explore how HA cleavage with hyaluronidase triggers inflammatory signaling via CD44 and/or TLR4, leading to endothelial dysfunction. Lastly, we will test the therapeutic potential of H-HA in restoring endothelial integrity following PT/HS and examine the role of CD44 in these outcomes using CD44 knockout mice. This application presents a comprehensive and rigorous approach to uncovering new mechanisms of endotheliopathy that drive poor outcomes after trauma. Combined with the established mentorship and professional development opportunities, completion of this training plan will provide an exceptional foundation for the applicant’s future career as an academic biomedical researcher.


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: 2026 ( Subtotal = $41,582 )
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Blood Diseases and Resources Research	001	1	7/21/2026	NEW	$0
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Blood Diseases and Resources Research	002	1	7/21/2026	NEW	$0
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Blood Diseases and Resources Research	000	1	7/21/2026	NEW	$41,582
														Subtotal = $41,582

Grand Total All Awards = $41,582

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Hyaluronan-Mediated Signaling in Trauma-Induced Endotheliopathy

Award Number: F31HL184785

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer