# RORalpha and Hepatic Zonal Regulation

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $344,250

## Abstract

The restricted expression of specific hepatic genes in pericentral or periportal regions of
the adult liver, a phenomenon known as zonal regulation, is a fascinating aspect of liver
biology. Elegant studies in the past 10 years have uncovered the role of the b-catenin
signaling pathway in controlling zonal expression. Our recent studied using a novel
mouse model system developed by us indicates that the retinoic acid-related orphan
receptor alpha (RORa) also plays a role in controlling zonal gene expression.
Furthermore, studies in other tissues have shown that RORa contributes to the
differentiation and proliferation of stem cells, but this property has not been evaluated in
the liver. We propose to use genetically modified mice and contemporary high-
throughput genomic technologies to explore the role of RORa in the function and stem
cell properties of pericentral hepatocytes. Since many hepatotoxins, including ethanol,
and pharmaceuticals, such as acetaminophen, specifically damage pericentral
hepatocytes, a better understanding of the mechanisms controlling gene expression in
and the self-renewing properties of this subpopulation of hepatocytes will help develop
strategies to reduce hepatocyte injury in humans.

## Key facts

- **NIH application ID:** 10179359
- **Project number:** 5R01DK074816-12
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Brett Spear
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2007-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179359

## Citation

> US National Institutes of Health, RePORTER application 10179359, RORalpha and Hepatic Zonal Regulation (5R01DK074816-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10179359. Licensed CC0.

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