Wednesday, July 30, 2025 7/30/2025

The role of cAMP signaling changes in alcoholic liver disease

Award Number: F30AA017809
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: 08/01/2008
PERIOD OF PERFORMANCE END DATE: 07/31/2013

Group Awards By:

View Award Description

The role of cAMP signaling changes in alcoholic liver disease - DESCRIPTION (provided by applicant): Chronic consumption of alcohol can lead to pathological developments in multiple organ systems, and much morbidity and mortality. While these pathological changes are well recognized, the mechanisms by which they occur remain elusive. In the liver, chronic alcohol consumption leads to changes in hormone signal transduction pathways, which may play a role in the etiology of alcoholic liver disease (ALD). The goal of this project is to understand the role of changes in cyclic-AMP (cAMP) signaling in the development of mitochondrial changes that may participate in the progression to ALD. We will pursue the following specific aims 1) cAMP signaling is increased in hepatocytes from animals chronically fed alcohol and that this increase leads to an increase in Protein Kinase A (PKA) activity, 2) increased PKA activity, potentially coupled with altered PKA localization, is responsible for mitochondrial localization of the Cytochrome P450 2E1 (CYP2E1) observed during chronic alcohol consumption, and 3) increased PKA activity is responsible for increased calcium mobilization and subsequent increased mitochondrial calcium loading in response to inositol 1,4,5-trisphosphate (IPS) -dependent hormones. These factors are proposed to act together to cause mitochondrial damage and decreased cell viability. Our central hypothesis is that increased mitochondrial CYP2E1, coupled with altered mitochondrial calcium homeostasis, may be largely responsible for the mitochondrial damage and dysfunction seen in livers of chronic abusers of alcohol. These aims will be assessed using single-cell fluorescence imaging, with calcium sensitive dyes and fluorescence energy resonance transfer (FRET) probes for mitochondrial calcium and cAMP production, immunocytochemistry to assess PKA localization, western blots to determine CYP2E1 localization and expression, and molecular-based kits for cAMP production and PKA activity. Information gained from these experiments will contribute to a better understanding of alterations in mitochondrial functioning in ALD, and may ultimately contribute to improved therapeutic treatments. Relevance: Diseases associated with alcohol abuse are major public health concerns in the United States due to a number of well-documented pathological conditions. Alcohol-induced liver disease is responsible for much of the morbidity and mortality associated with alcohol abuse, yet the exact mechanisms by which such conditions occur remain elusive. The goal of this project is to understand how changes in cellular signaling can lead to mitochondrial dysfunction and ultimately tissue damage and disease progression.


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: 2017 ( Subtotal = -$30,398 )
2017	2012	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Alcohol Research Programs	000	6	4/19/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$30,398
														Subtotal = -$30,398

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol Research Programs	000	5	12/30/2013	NON-COMPETING CONTINUATION	$2,660
2014	2012	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Alcohol Research Programs	001	6	12/30/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$2,660
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Alcohol Research Programs	001	6	8/8/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$35,112
2013	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol Research Programs	000	5	8/8/2013	NON-COMPETING CONTINUATION	-$35,112
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $40,114 )
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol Research Programs	000	5	7/6/2012	NON-COMPETING CONTINUATION	$40,114
														Subtotal = $40,114

Issue Date FY: 2011 ( Subtotal = $39,682 )
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol Research Programs	000	4	8/1/2011	NON-COMPETING CONTINUATION	$39,682
														Subtotal = $39,682

Issue Date FY: 2010 ( Subtotal = $28,894 )
2010	2010	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol National Research Service Awards for Research Training	000	3	7/31/2010	NON-COMPETING CONTINUATION	$28,894
														Subtotal = $28,894

Issue Date FY: 2009 ( Subtotal = $28,690 )
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol National Research Service Awards for Research Training	000	2	7/22/2009	NON-COMPETING CONTINUATION	$28,690
														Subtotal = $28,690

Issue Date FY: 2008 ( Subtotal = $28,486 )
2008	2008	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Alcohol National Research Service Awards for Research Training	000	1	7/29/2008	NEW	$28,486
														Subtotal = $28,486

Grand Total All Awards = $135,468

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of cAMP signaling changes in alcoholic liver disease

Award Number: F30AA017809

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: 08/01/2008

PERIOD OF PERFORMANCE END DATE: 07/31/2013

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer