# Research Project 2: Genome-wide epigenetic changes regulating specific transcription factors determine HSC phenotype in alcohol-induced liver fibrosis

> **NIH NIH P50** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $113,867

## Abstract

RESEARCH PROJECT 2 – ABSTRACT
Chronic alcohol abuse results in hepatic fibrosis and cirrhosis which is driven by activation of
myofibroblasts that synthesize the fibrous scar. Using the experimental model of intragastric (IG)
alcohol feeding in mice, we and the others have demonstrated that activated Hepatic Stellate
Cells (aHSCs) are the major source of myofibroblasts in alcoholic liver fibrosis. Therefore, aHSCs
are the primary targets for antifibrotic therapy. Our central hypothesis is that genome-wide
epigenetic changes regulating specific transcription factors determine HSC phenotype in alcohol-
induced liver fibrosis in patients and in mice. Our strategy is based on the breakthrough
technologies of the past 2 years, which enable us for the first time to perform a) RNA-Seq on
individual HSCs to explore the diversity of HSC phenotypes in human alcoholic liver disease
(AIM2A) and experimental model of IG alcohol feeding in mice (AIM1A). In particular, if a specific
transcription factor, such as NF-1, is critical in both human and mouse aHSCs (AIM2B), we can
then directly test its role in vivo by selectively knocking out the gene in a conditional knockout
mouse subjected to alcohol-induced liver fibrosis (AIM1B). By carefully comparing human and
mouse alcohol-induced liver fibrosis and the concomitant activation of hepatic stellate cells, we
can translate the results of our mouse studies into the human disease.

## Key facts

- **NIH application ID:** 9886170
- **Project number:** 5P50AA011999-22
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** HIDEKAZU TSUKAMOTO
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $113,867
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886170

## Citation

> US National Institutes of Health, RePORTER application 9886170, Research Project 2: Genome-wide epigenetic changes regulating specific transcription factors determine HSC phenotype in alcohol-induced liver fibrosis (5P50AA011999-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9886170. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*