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RNA Modification Changes in Alcohol-Associated Liver Disease

Award Number: R21AA031563
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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RNA Modification Changes in Alcohol-Associated Liver Disease - Abstract. Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases. The progressive nature of alcohol-associated liver disease (ALD) has been well described, but the complex interactions under which these pathologies evolve remain only partially elucidated. Based on our preliminary study, free nucleosides and nucleosides hydrolyzed from total RNA are altered in mice treated with alcohol and in a human liver cell line, HepaRG, treated with acetaldehyde. We also observed significant changes in the serum and urine of patients with different stages of ALD. Therefore, we hypothesize that alcohol consumption affects RNAs' chemical modification and contributes to ALD development and progression. To prove this hypothesis, we will treat mice with alcohol and first map the chemical modifications on RNAs by isolating different types of RNAs from mouse liver, digesting them into nucleosides and oligonucleotides, and detecting the site- specific modification on each RNA using comprehensive 2DLC-MS (Aim 1). And then, RNA modification variation will be studied between alcohol fed and normal fed mice at the RNA level, and the underlying mechanism will be uncovered by detecting the expression of the corresponding enzymes (Aim 2). 1


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 = $208,855 )
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Alcohol Research Programs	001	2	8/25/2025	NON-COMPETING CONTINUATION	$217,019
2025	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Alcohol Research Programs	000	1	10/24/2024	NEW	-$8,164
														Subtotal = $208,855

Issue Date FY: 2024 ( Subtotal = $191,381 )
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Alcohol Research Programs	000	1	8/14/2024	NEW	$191,381
														Subtotal = $191,381

Grand Total All Awards = $400,236

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RNA Modification Changes in Alcohol-Associated Liver Disease

Award Number: R21AA031563

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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