# Defining the role of a novel hexokinase in alcoholic liver disease

> **NIH NIH R21** · LOYOLA UNIVERSITY CHICAGO · 2024 · $221,375

## Abstract

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.

## Key facts

- **NIH application ID:** 10930893
- **Project number:** 5R21AA031361-02
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Wei Qiu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $221,375
- **Award type:** 5
- **Project period:** 2023-09-18 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930893

## Citation

> US National Institutes of Health, RePORTER application 10930893, Defining the role of a novel hexokinase in alcoholic liver disease (5R21AA031361-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10930893. Licensed CC0.

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