Wednesday, December 17, 2025 12/17/2025

Mechanosensitive M7G epitranscriptome in endothelial health and disease

Award Number: R01HL155909
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/22/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Mechanosensitive M7G epitranscriptome in endothelial health and disease - Project Summary RNA chemical modifications, collectively referred to as the “epitranscriptome”, have recently emerged as a novel layer of molecular control of gene expression. Most epitranscriptomic studies address N6- methyladenosine (m6A) of mRNA in human cancers. The molecular identity of endothelial mRNA epitranscriptome and its potential role in regulating vascular functions remains a major knowledge gap. Recent studies suggested that mammalian mRNAs are broadly chemically modified and mRNA modifications occur in a cell-type and cell-state dependent manner. N6-methyladenosine (m6A), the most abundant internal (outside of the 5’ cap) methylation in mammalian mRNA, has been linked to critical biological processes such as proliferation, development, and stem cell differentiation. Only few recent studies addressed the potential role of mRNA m6A in cardiomyocyte remodeling and endothelial activation. We recently discovered the presence of a new chemical modification, N7-methylguanosine (m7G) in mammalian mRNA. Systematic m7G mapping in endothelial mRNA and its potential role in vascular pathophysiology is an unexplored territory. Vascular endothelium is dynamically regulated by blood flow via mechano-transduction mechanisms. Endothelial activation by disturbed flow contributes to a wide range of vascular diseases. Atherosclerosis preferentially develops in arterial sites where endothelium is activated by local disturbed flow whereas unidirectional flow promotes endothelial health. Current atherosclerosis therapies mainly target systematic risk factors but not the vasculature per se. This underscores the significance and unique opportunity to identify and target novel mechanosensitive mechanisms in vascular endothelium. We have generated very strong data demonstrating that the mRNA m7G is dynamically regulated in endothelium by hemodynamics. Unidirectional flow (UF) markedly increases m7G but not m6A in endothelial mRNAs. Moreover, Methyltransferase-Like 7A (METTL7A) is a novel m7G writer governing the UF-induced mRNA m7G methylation in endothelium. The overall goal of this project is to delineate the novel molecular mechanisms by which mechano-sensitive METTL7A governs endothelial mRNA m7G and regulates vascular functions in vitro and in vivo. Moreover, we will devise innovative precision nanomedicine approaches targeting METTL7A-mediated pathways to treat atherosclerosis.


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 CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	000	4	11/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $696,981 )
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	001	4	9/3/2025	NON-COMPETING CONTINUATION	$69,699
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	000	4	11/6/2024	NON-COMPETING CONTINUATION	$627,282
														Subtotal = $696,981

Issue Date FY: 2024 ( Subtotal = $683,041 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	001	3	6/26/2024	NON-COMPETING CONTINUATION	$55,759
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	000	3	11/27/2023	NON-COMPETING CONTINUATION	$627,282
														Subtotal = $683,041

Issue Date FY: 2023 ( Subtotal = $696,981 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	000	2	12/1/2022	NON-COMPETING CONTINUATION	$627,282
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	001	2	3/6/2023	NON-COMPETING CONTINUATION	$69,699
														Subtotal = $696,981

Issue Date FY: 2022 ( Subtotal = $696,981 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Cardiovascular Diseases Research	000	1	12/21/2021	NEW	$696,981
														Subtotal = $696,981

Grand Total All Awards = $2,773,984

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Mechanosensitive M7G epitranscriptome in endothelial health and disease

Award Number: R01HL155909

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/22/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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