# Project 2: Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure

> **NIH NIH P42** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $392,212

## Abstract

Project Summary/Abstract:
Superfund site toxicants pose a significant hazard to human health, in part through their ability to alter patterns
of gene expression. One of the most prevalent diseases, toxicant-associated steatohepatitis (TASH), is
phenotypically similar to nonalcoholic steatohepatitis (NASH) without the underlying obesity. Building on this
similarity, this project will provide mechanistic insight into TASH-induced liver damage and models of exposure.
With a focus on the epigenetic and immune responses, the overall goal of the project is to identify potential
intervention or prevention therapies and/or therapeutic targets. In Aim 1 we will explore the role of regulatory
enhancers, key genomic mediators of tissue fibrosis, in mouse models of TASH by mapping injury-induced
epigenetic changes in stellate cells, hepatocytes, and immune cells. In parallel studies, the therapeutic efficacy
of epigenetically-targeted small molecule modulators will be determined in both intervention and prevention
models of TASH. In Aim 2 we will profile the immune response to toxicant-induced liver damage in mice during
the initial injury, damage/repair, and resolution stages. Based on these findings, potential immune-targeted
therapies for the treatment TAFLD and TASH will be explored. In Aim 3, the epigenetic and immunological
consequences of chronic toxicant exposure will be explored in a novel genetic mouse model of TAFLD
(SMRTRID mice). In summary, this project will provide valuable insight on the molecular mechanisms underlying
TAFLD and TASH as well as a roadmap for potential new therapies.

## Key facts

- **NIH application ID:** 10137944
- **Project number:** 5P42ES010337-20
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RONALD M EVANS
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,212
- **Award type:** 5
- **Project period:** 2000-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137944

## Citation

> US National Institutes of Health, RePORTER application 10137944, Project 2: Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure (5P42ES010337-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137944. Licensed CC0.

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