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Endothelial glycocalyx shedding in septic injury

Award Number: R01GM142110
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: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Endothelial glycocalyx shedding in septic injury - PROJECT SUMMARY/ABSTRACT Sepsis is a critical illness arising from dysregulated host response to infection where invading pathogens elicit an adverse systemic inflammatory response that affects multiple organs and tissues. Currently, there are limited therapies that effectively treat this disease. The overarching goal of our work is to identify new molecular targets that can potentially serve as diagnostics or therapeutics for prevention and treatment of sepsis. This project focuses on glycocalyx shedding as not merely a consequence, but a critical cause, of inflammatory injury. Specifically, we hypothesize that bacterial infection promotes disintegrin metalloprotease (ADAM) upregulation and activity to shed glycocalyx molecules on endothelial surface and release their fragments into the circulation, which act as inflammatory signals to mediate microcirculatory dysfunction and barrier leakage by triggering endothelial cytoskeleton-junction responses. This novel concept will be tested by completing two aims: Aim 1 to characterize the molecular property of glycocalyx shedding products and function in microvascular inflammation during sepsis; Aim 2 to elucidate the molecular mechanisms of endothelial glycocalyx shedding and barrier injury. We propose a multifaceted approach based on an innovative design that integrates peptidomics, proteomics and nanotechnology with multispectral photoacoustic tomography, super-resolution confocal and 3D intravital microscopic imaging. Functionally viable human lungs and microvessels serve as the primary models, which are complemented by animal models and cell experiments. Microvascular barrier structure and function will be examined in-depth at the organ, tissue and cell levels under pathophysiologically relevant conditions of bacterial infection. We expect to gain novel insights that will not only fill the knowledge gaps in understanding the molecular mechanisms of septic injury, but also contribute to the development of effective therapeutics against infectious diseases. The proposed human organ studies further highlight the translational values of our work.


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: 2025 ( Subtotal = $420,397 )
2025	2025	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	4	11/8/2024	NON-COMPETING CONTINUATION	$420,397
														Subtotal = $420,397

Issue Date FY: 2024 ( Subtotal = $465,526 )
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	001	3	6/12/2024	NON-COMPETING CONTINUATION	$46,553
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	3	11/15/2023	NON-COMPETING CONTINUATION	$418,973
														Subtotal = $465,526

Issue Date FY: 2023 ( Subtotal = $465,761 )
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	2	12/5/2022	NON-COMPETING CONTINUATION	$419,185
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	001	2	2/15/2023	NON-COMPETING CONTINUATION	$46,576
														Subtotal = $465,761

Issue Date FY: 2022 ( Subtotal = $470,652 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	1	11/29/2021	NEW	$470,652
														Subtotal = $470,652

Grand Total All Awards = $1,822,336

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Endothelial glycocalyx shedding in septic injury

Award Number: R01GM142110

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: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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