# Ethanol Effects on the Transcriptional Regulatory Network in Liver Regeneration

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2022 · $586,170

## Abstract

PROJECT SUMMARY
Liver regeneration is a program with a broad range of applications that is designed to maintain a healthy state of
the tissue. When the liver gets exposed to severe damage, there is an active repair response that can use the
functional cells and help them expand to the optimal size for that tissue. Many toxins and related treatments are
capable of damaging the liver tissue to the point where only a modest quantity of liver function remains. However,
under these conditions the liver is uniquely positioned to repair its structure and recover the original tissue mass
and it is these processes that help maintain liver function, referred to as Liver Regeneration. The repair process
has multiple productive applications. However, it may be derailed by processes such as the heavy consumption
of alcoholic beverages and as a result, it is subject to monitoring that may derail its usefulness. Unusually, we
recently discovered that exposure of our rats to ethanol in their food will chronically lead to a health crisis upon
liver injury only in male rats, whereas female rats did not suffer from this affliction. This finding matched our prior
studies that had demonstrated that females are more resistant to some types of alcohol-related injury. Moreover,
we have developed a research program in which males are subject to a variety of alcohol-related injuries that
females are protected from. These findings are correlated with the individual tests for sensitivity of the liver
regeneration process resolved in specific interactions. The Specific Aims are summarized here to enable the
recovery of the critical points to identify where the problems are located. These aims include (a) studies to test
the hypothesis that ethanol affects the tissue state balance of metabolic compensatory adjustments and
proliferation to disrupt the integrate response to PHx, (b) studies to test the hypothesis that interlinked cell state
transitions across multiple cell types govern the integrative response to ethanol-mediated disruption in a sex-
dependent manner; and (c) studies to identify the renormalization of the ethanol-blocked deficiencies in
hepatocyte proliferation by normalizing early phase transcriptional regulatory events; We will bridge between
animal models and human ALD in these Aims by evaluating the animal study results across a spectrum of human
ALD conditions to identify commonalities and translatable mechanisms of ethanol action and putative targets for
intervention.

## Key facts

- **NIH application ID:** 10470849
- **Project number:** 5R01AA018873-12
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Ramon Bataller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $586,170
- **Award type:** 5
- **Project period:** 2009-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470849

## Citation

> US National Institutes of Health, RePORTER application 10470849, Ethanol Effects on the Transcriptional Regulatory Network in Liver Regeneration (5R01AA018873-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10470849. Licensed CC0.

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