Friday, January 2, 2026 1/2/2026

TRPV4 Regulates Mechanosensitive Macrophage Functions in Lung Injury

Award Number: R01HL155064
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

TRPV4 Regulates Mechanosensitive Macrophage Functions in Lung Injury - PROJECT SUMMARY/ABSTRACT Overwhelming bacterial pneumonia injures and stiffens the lung leading to acute respiratory distress syndrome (ARDS) that carries a mortality of up to 50%. Given many failed pharmacologic treatments, ARDS management is supportive. ARDS is a consequence of endothelial and alveolar epithelial injury followed by recruitment and accumulation of inflammatory cells in the injured alveolus. Macrophages are the key effector cells in the lung injury process by phagocytizing invading pathogens and secreting cytokines. We have identified that the mechanosensitive ion channel, transient receptor potential vanilloid 4 (TRPV4), protects the lung from injury in an in vivo model of chronic Pseudomonas aeruginosa pneumonia through a novel mechanism of MAPK molecular switching, from JNK to p38. However, the key intracellular signaling molecules that link TRPV4 to the MAPK molecular switch and the precise cell phenotype/function that increases phagocytosis/bacterial clearance and decreases lung injury are unknown. Uncovering novel mechanosensitive signaling mechanisms that control macrophage function when the lung is injured/stiff will fulfill the unmet medical need to design therapies to treat this devastating disease. This research proposal investigates the mechanism whereby TRPV4 adapts the host defense to enhance the lung injury response to P. aeruginosa pneumonia. The long-term goal of our studies is to deduce TRPV4-dependent intracellular signals in macrophages that protect and resolve pneumonia- associated lung injury. Our preliminary data show that macrophage TRPV4 signals through specific intracellular signaling molecules to alter the macrophage activation response in vitro. Therefore, we propose the novel hypothesis: TRPV4 tailors the host response to protect the lung from injury after P. aeruginosa pneumonia through macrophage intracellular signals. This hypothesis will be tested through three interrelated, but independent specific aims: (1) to determine the mechanism whereby TRPV4 enhances macrophage phagocytosis, (2) to determine the mechanism whereby TRPV4 limits pro-inflammatory cytokine production, and (3) to compare the role of TRPV4 in alveolar vs interstitial macrophages in bacterial clearance and infection-induced lung injury after P. aeruginosa pneumonia in mice. Our proposal is innovative in concept as it is the first to implicate a matrix stiffness-sensing cation channel (TRPV4) and its intracellular signaling molecules in bacterial pneumonia and associated lung tissue injury. The proposed research is significant and relevant to the NIH’s mission as we aim to explore how TRPV4 in macrophages integrates the infection and matrix mechanical signaling to protect the lung from injury. The pathways discovered will identify novel therapeutic targets to treat infection-associated ARDS.


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	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	5	11/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $425,473 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	5	2/26/2025	NON-COMPETING CONTINUATION	$382,925
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	001	5	8/5/2025	NON-COMPETING CONTINUATION	$42,548
														Subtotal = $425,473

Issue Date FY: 2024 ( Subtotal = $416,964 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	4	1/30/2024	NON-COMPETING CONTINUATION	$382,925
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	001	4	6/15/2024	NON-COMPETING CONTINUATION	$34,039
														Subtotal = $416,964

Issue Date FY: 2023 ( Subtotal = $425,473 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	001	3	3/15/2023	NON-COMPETING CONTINUATION	$42,548
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	3	1/14/2023	NON-COMPETING CONTINUATION	$382,925
														Subtotal = $425,473

Issue Date FY: 2022 ( Subtotal = $429,075 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	2	1/27/2022	NON-COMPETING CONTINUATION	$386,166
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	001	2	6/14/2022	NON-COMPETING CONTINUATION	$42,909
														Subtotal = $429,075

Issue Date FY: 2021 ( Subtotal = $400,496 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	001	1	6/19/2021	NEW	$40,049
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Lung Diseases Research	000	1	1/26/2021	NEW	$360,447
														Subtotal = $400,496

Grand Total All Awards = $2,097,481

Top

All Categories

About

Search

Reports

Data Submission

Award Information

TRPV4 Regulates Mechanosensitive Macrophage Functions in Lung Injury

Award Number: R01HL155064

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer