# Nuclear Receptors as Novel Therapeutic Targets for Wilson’s Disease

> **NIH NIH K01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $148,956

## Abstract

Project Summary/Abstract
 The goal of this proposal is to extend my training as an independent scientist in the field of molecular
hepatology and discover mechanisms of nuclear receptor regulation of hepatic metabolism. To this end, I have
selected the Molecular and Cellular Biology Department at Baylor College of Medicine to continue my transition
to become an independent investigator at an academic institution. This proposal outlines an extensive
Research Strategy that is complemented by several areas of training, which includes several courses directly
related to my studies in Specific Aim 1, meeting with my junior faculty research committee, and attendance and
participation of multiple seminars throughout the Texas Medical Center. My Research Strategy will determine
whole genomic-changes in nuclear receptor binding in a Wilson's disease animal model (Atp7b-/- mouse).
Wilson's disease is an autosomal recessive disorder caused by loss of function mutations in the Cu-
transporting P-type ATPase, ATP7b, which results in a variety of symptoms, including hepatic copper
accumulation, cholestasis, cirrhosis, liver failure, and neurological dysfunction. Treatments for Wilson's
disease are limited to chelation therapy, zinc therapy, or liver transplantation. Chelation therapy has been
associated with several side-effects and poor patient compliance, and uncontrolled Wilson's disease can result
in liver failure and requires liver transplantation for patient survival. Despite the severity of Wilson's disease,
insights regarding copper-mediated changes in metabolism are limited. My post-doctoral studies established a
defect in nuclear receptor activity in the Atp7b-/- mouse and Wilson's disease patients. The proposed K01
experiments continue those studies to determine the broader changes in nuclear receptor promoter occupancy
and target gene mRNA expression, as well as test if targeting the nuclear receptors decreases the liver
pathology observed in the Atp7b-/- mouse.

## Key facts

- **NIH application ID:** 10085633
- **Project number:** 5K01DK111716-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Clavia Ruth Wooton-Kee
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $148,956
- **Award type:** 5
- **Project period:** 2017-02-17 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085633

## Citation

> US National Institutes of Health, RePORTER application 10085633, Nuclear Receptors as Novel Therapeutic Targets for Wilson’s Disease (5K01DK111716-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085633. Licensed CC0.

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