Thursday, January 1, 2026 1/1/2026

Mechanisms and Treatment of SARS-CoV-2 induced Lung Endothelial Injury

Award Number: R01HL162308
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Mechanisms and Treatment of SARS-CoV-2 induced Lung Endothelial Injury - PROJECT SUMMARY / ABSTRACT Coronavirus disease 2019 (COVID-19) is a devastating systemic inflammatory syndrome caused by the coronavirus SARS-CoV-2 which has resulted in over 500,000 deaths in the US during the past year, with this high rate of mortality being attributed in large part to the development of Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 entry into cells requires the direct binding of the SARS-CoV-2 spike (S)-protein to the principal host protease-TMPRSS2 and the angiotensin converting enzyme 2 (ACE-2) receptors which are expressed in multiple host cell types. The development of efficacious vaccines to prevent the spread of SARS-CoV-2 represents a tremendous advance that will help curb the COVID-19 pandemic, however the emergence of variants of concern such as the B1.1.7, P1 and B1.351 which can evade the neutralizing responses of the vaccine-induced humoral immune response underscores the urgent need to develop novel therapeutics to complement the vaccination efforts. Based on our provocative Supporting Data, we have formulated the overarching hypothesis that SARS-CoV-2 induced lung endothelial injury is a requisite element of COVID-19 induced maladaptive inflammatory injury that can be therapeutically targeted. We propose the following specific aims: In Aim 1, we will define the nature and underlying mechanisms of lung endothelial injury underlying COVID-19-induced ALI/ARDS. We will test the hypothesis that the degree of lung endothelial injury is a key determinant of the overall pathogenicity and mortality of multiple SARS- CoV-2 variants. We will establish SARS-CoV-2-induced lung vascular injury and compensatory lung endothelial regeneration using two complementary humanized ACE2 mouse models, EC-specific genetic lineage tracing, genetic stabilization of VE-cadherin and single cell RNA-Sequencing. In Aim 2, we will define the efficacy and optimal temporal windows for two targeted pharmacological therapeutic strategies in preventing and resolving SARS-CoV- 2 induced lung endothelial injury. We will test the hypothesis that an engineered soluble hACE-2 peptide has a higher therapeutic efficacy than the wildtype hACE-2 peptide in reducing lung endothelial injury as well as long-term EC reprogramming by preventing viral entry and dissemination of multiple SARS-CoV-2 variants. We will test the corollary hypothesis and that targeted inhibition of IL1β-signaling using a modified IL-1 Receptor antagonist is protective against the feed-forward inflammatory loop and endothelial injury induced by multiple SARS-CoV2 variants. We will use two hACE-2 mouse models as well as compare distinct routes of delivery (intratracheal versus intravenous) and identify the optimal temporal windows for the therapeutic intervention.


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 = $0 )
2026	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	000	4	11/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $798,125 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	001	4	2/26/2025	NON-COMPETING CONTINUATION	$665,104
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	002	4	8/15/2025	NON-COMPETING CONTINUATION	$73,900
2025	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	000	3	12/21/2024	NON-COMPETING CONTINUATION	$59,121
														Subtotal = $798,125

Issue Date FY: 2024 ( Subtotal = $665,104 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	000	3	1/26/2024	NON-COMPETING CONTINUATION	$665,104
														Subtotal = $665,104

Issue Date FY: 2023 ( Subtotal = $739,004 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	000	2	1/24/2023	NON-COMPETING CONTINUATION	$739,004
														Subtotal = $739,004

Issue Date FY: 2022 ( Subtotal = $739,004 )
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Lung Diseases Research	000	1	2/1/2022	NEW	$739,004
														Subtotal = $739,004

Grand Total All Awards = $2,941,237

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Mechanisms and Treatment of SARS-CoV-2 induced Lung Endothelial Injury

Award Number: R01HL162308

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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