# Epigenetic regulation in liver fibrosis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $457,057

## Abstract

Project Summary
 Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% adults in the US. NAFLD initially
manifests hepatic steatosis and progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and even cirrhosis
or hepatocellular carcinoma. Liver fibrosis, a condition of elevated accumulation of extracellular matrix in the
liver, is a strong indicator of NASH severity. In most NASH patients, environmental factors such as high-calorie
diets and sedentary lifestyle are primary contributors to the disease development. Those environmental cues
often modulate epigenetic and transcription factors to acquire long-term effects. In our preliminary study, we
have identified Sirtuin 6 (Sirt6) as a key suppressor of liver fibrosis. To further investigate the role of Sirt6 in the
pathogenesis of liver fibrosis, we plan to carry out both in vitro and in vivo experiments using cell and animal
models. Hepatic stellate cells are generally considered as a major contributor to the production of extracellular
matrix in the liver after chronic liver injury. Therefore, we will focus on the regulation of hepatic stellate cells by
Sirt6 at molecular, cellular, and tissue levels. It is expected that the proposed pathophysiological and
mechanistic investigation of liver fibrosis in this application will uncover key pathways or network that is
controlled by Sirt6. Moreover, the knowledge gained from this project can help develop therapeutic
interventions for hepatic fibrosis.

## Key facts

- **NIH application ID:** 10172893
- **Project number:** 5R01DK121925-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** X. Charlie Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,057
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172893

## Citation

> US National Institutes of Health, RePORTER application 10172893, Epigenetic regulation in liver fibrosis (5R01DK121925-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10172893. Licensed CC0.

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