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Uncovering the functional and mechanistic dysregulation of monocytes after abstinence and post-abstinence drinking

Award Number: F31AA031600
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/12/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026
AWARD TERMINATION DATE: 10/15/2026

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Uncovering the functional and mechanistic dysregulation of monocytes after abstinence and post-abstinence drinking - Over 85% of individuals 18 years and older within the United States (US) consume alcohol. More importantly, a staggering 25.8% and 6.3% are classified by the National Institute on Alcohol Abuse and Alcoholism criteria as binge or heavy drinkers, respectively, making alcohol the 3rd leading cause of preventable death. Chronic heavy drinking (CHD) increases the incidence of heart disease, stroke, cancer, and alcoholic liver disease. CHD is also associated with heightened susceptibility to bacterial/viral pathogens and tissue repair mechanisms, suggesting alcohol consumption negatively impacts the immune system. Indeed, studies from our group and others have reported functional, transcriptional, and epigenetic modifications in peripheral monocytes and tissue-resident macrophages with CHD, skewing them toward a hyper-inflammatory phenotype while impairing pathogen defense mechanisms. Despite the significant contribution of aberrant monocyte/macrophage responses to CHD- induced organ injury, no studies to date have investigated the effects of abstinence and post-abstinence drinking on these critical cells. Organs and organ systems after alcohol consumption (brain, liver, lung) are challenging to interrogate throughout repeated bouts of abstinence and post-abstinence drinking. Since circulating monocytes are precursors of some tissue-resident macrophages, investigating the effects of abstinence and relapse on circulating monocytes will provide greater insight into how CHD dysregulates organs and organ systems. In this application, we will leverage a rhesus macaque model of voluntary ethanol self-administration to test the hypothesis that CHD induces persistent functional, transcriptional, and epigenetic changes in peripheral monocytes that are not reversed by short periods of abstinence and are exacerbated by repeated bouts of abstinence and post-abstinence drinking. This hypothesis will be tested using a multi- pronged approach using multiplex ELISA, flow cytometry, single cell omics, and metabolic assays after a 28-day abstinence and post-abstinence drinking episodes. These experiments will provide deeper insight into the persistence of CHD-induced immune modifications in complex organs and organ systems. This understanding could identify novel druggable targets that decrease alcohol cravings or organ damage/opportunistic infections that occur after CHD.


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: 2027 ( Subtotal = -$3,239 )
2027	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	2	10/15/2026	TERMINATION	-$3,239
														Subtotal = -$3,239

Issue Date FY: 2025 ( Subtotal = $35,420 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	2	8/12/2025	NON-COMPETING CONTINUATION	$35,420
														Subtotal = $35,420

Issue Date FY: 2024 ( Subtotal = $34,856 )
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	1	8/1/2024	NEW	$34,856
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	001	1	8/1/2024	NEW	$0
														Subtotal = $34,856

Grand Total All Awards = $67,037

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Uncovering the functional and mechanistic dysregulation of monocytes after abstinence and post-abstinence drinking

Award Number: F31AA031600

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/12/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

AWARD TERMINATION DATE: 10/15/2026

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