# The role of protein O-GlcNAcylation in liver injury

> **NIH NIH P01** · YALE UNIVERSITY · 2020 · $309,873

## Abstract

Project Summary/Abstract 
The liver is a major metabolic organ responsible for maintaining whole-body homeostasis in a changing 
environment. Given the worldwide use of alcohol, the epidemic of obesity and viral infection, liver damage is 
common in clinical practice. The molecular mechanisms that control the balance between hepatocyte life and 
death in response to chronic liver injury remain largely elusive. O-linked β-N-acetylglucosamine (O-GlcNAc) 
modification has emerged as an important regulatory mechanism underlying normal liver physiology and 
metabolic disease. This prevalent and dynamic post-translational modification is controlled by O-GlcNAc 
transferase (OGT) and O-GlcNAcase (OGA). We recently found that liver-specific OGT knockout mice develop 
hepatomegaly, ballooning degeneration, and fibrosis in the liver. We therefore hypothesize that OGT acts as a 
critical molecular switch between hepatocyte survival and death in response to chronic liver injury. To 
test this hypothesis, we propose to undertake three specific aims. Aim 1 will define the role of OGT in 
pathogenesis of liver injury; Aim 2 will identify the critical targets of OGT in hepatocyte survival and death; Aim 
3 will determine the functional importance of OGT regulation of necroptosis in liver injury. Successful 
completion of this project will provide critical insights into the role of OGT in regulating the balance between 
hepatocyte survival and death and the onset of liver injury. Detailed investigation of liver-specific OGT 
knockout mice will likely establish a useful mouse model that recapitulates features of human liver injury, and 
facilitate therapeutic target identification for prevention and treatment of chronic liver disease.

## Key facts

- **NIH application ID:** 9931211
- **Project number:** 5P01DK057751-20
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Xiaoyong Yang
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,873
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931211

## Citation

> US National Institutes of Health, RePORTER application 9931211, The role of protein O-GlcNAcylation in liver injury (5P01DK057751-20). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9931211. Licensed CC0.

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