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Defining the role of a novel hexokinase in alcoholic liver disease

Award Number: R21AA031361
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: 09/18/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Defining the role of a novel hexokinase in alcoholic liver disease - Abstract Alcoholic liver disease (ALD) is one of the primary causes of chronic liver disease worldwide and cirrhosis- associated deaths in the United States. Current treatments for ALD are not satisfactory. Novel therapeutic strategies are desperately needed, which warrants a further understanding of the mechanisms of ALD development. Dysregulation of glucose metabolism and glycolysis plays a critical role in ALD development. As key enzymes of phosphorylation of glucose, hexokinases play critical roles in regulating glucose metabolism and glycolysis. Recently, the hexokinase domain containing 1 (HKDC1), a novel hexokinase that catalyzes the phosphorylation of glucose and plays a vital role in cellular glucose and liver metabolism, was identified as the most up-regulated kinase in patients with alcoholic hepatitis. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. We recently also found that HDKC1 expression is increased in human and mouse alcoholic steatohepatitis (ASH) samples compared to normal livers. Based on the existing literature, we hypothesize that alcohol-induced HKDC1 expression promotes glycolysis and ATP production, thus serving as a protective mechanism against alcohol-induced hepatocyte death and ALD development. The Overall Objective of this grant is to answer three questions: 1) What impact does the excessive expression of HKDC1 have on ASH development? 2) Is HKDC1 indispensable for ASH development to occur? 3) How does EtOH lead to an elevation in HKDC1 expression? The results of this proposal could potentially reveal novel mechanisms for ALD pathogenesis and provide the groundwork for the development of novel treatment strategies for ALD.


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	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Alcohol Research Programs	000	2	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $221,375 )
2024	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Alcohol Research Programs	000	2	8/2/2024	NON-COMPETING CONTINUATION	$221,375
														Subtotal = $221,375

Issue Date FY: 2023 ( Subtotal = $182,875 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Alcohol Research Programs	000	1	9/18/2023	NEW	$182,875
														Subtotal = $182,875

Grand Total All Awards = $404,250

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Defining the role of a novel hexokinase in alcoholic liver disease

Award Number: R21AA031361

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: 09/18/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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