Thursday, July 3, 2025 7/3/2025

The proinflammatory functions of granzymes and their impact on endothelial inflammation/injury

Award Number: R21AI186960
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/22/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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The proinflammatory functions of granzymes and their impact on endothelial inflammation/injury - Project Summary While antiretroviral therapy successfully suppresses HIV replication, immune activation and inflammation persist, albeit at lower levels, and has been associated to as an important contributor of morbidity and mortality in PWH. The clinical significance of immune activation is the evidence that demonstrates that HIV- associated T cell immune activation and inflammation drive cardiovascular risk, independent of the traditional risk factors, duration of antiretroviral treatment, and CD4 counts. Persistent HIV reservoirs are independently associated with incident carotid plaque, and people with coronary artery atherosclerotic plaques show higher levels of HIV DNA compared to those without disease. The molecular pathways by which HIV contributes to the increased risk is largely unknown, and difficult the development of more targeted therapies. CD8 T cell immune activation is associated with endothelial inflammation and dysfunction, and in this study, we hypothesize that HIV-driven CD8 T cell immune activation promotes secretion of granzymes contributing to vascular inflammation/injury. We will test this hypothesis by: Aim1. Granzymes expression regulation by memory CD8 T cell subsets and virus-specific CD8 T cells recruited to the sites of vascular injury to define their proinflammatory vs cytotoxic potential. Aim2. Granzyme expressing CD8 T cells enhance atherosclerosis progression during infection. We will assess the extracellular contribution of granzymes and their impact in the progression of a disease during infection.


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 = $195,000 )
2025	2025	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	000	2	6/9/2025	NON-COMPETING CONTINUATION	$195,000
														Subtotal = $195,000

Issue Date FY: 2024 ( Subtotal = $210,600 )
2024	2024	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	000	1	7/22/2024	NEW	$210,600
														Subtotal = $210,600

Grand Total All Awards = $405,600

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The proinflammatory functions of granzymes and their impact on endothelial inflammation/injury

Award Number: R21AI186960

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/22/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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