# Hepatic protein-tyrosine phosphatase1B and alcoholic liver disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $186,438

## Abstract

ABSTRACT
Alcoholic liver disease (ALD) is a significant cause of liver-related death in the United States.
The disease covers a spectrum of disorders ranging from steatosis to alcoholic hepatitis and
may progress to cirrhosis and hepatocellular carcinoma. While the majority of heavy drinkers
develop fatty liver, only a minority will progress to alcoholic hepatitis, and 10-15% develop
cirrhosis. Despite the significant public health burden, there is currently no FDA-approved
pharmacotherapy for ALD indicating the urgent need to develop new therapies. Protein tyrosine
phosphatase 1B (PTP1B; encoded by Ptpn1) is a widely expressed phosphatase and an
established metabolic regulator. Given the beneficial effects of PTP1B deficiency and
pharmacological inhibition it is an attractive therapeutic target for metabolic diseases. To
investigate the role of PTP1B in ALD we will use a loss-of-function approach to investigate the
contribution of PTP1B in hepatocytes and hepatic stellate cells. Also, we will determine the
molecular mechanisms underlying hepatic PTP1B action and explore the potential preventative
and therapeutic value of PTP1B inhibition in ALD. Preliminary data demonstrated that liver-
specific PTP1B disruption attenuated ethanol-induced steatosis and inflammation in the chronic
plus binge mouse model of ALD. Moreover, hepatic PTP1B deficiency attenuated ethanol-
induced oxidative stress and inflammation. Together, these findings suggest that PTP1B
impacts hepatic function in ALD and that PTP1B pharmacological inhibition may present a
therapeutic approach in disease management.

## Key facts

- **NIH application ID:** 10020753
- **Project number:** 5R21AA027633-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Ming-Fo Hsu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,438
- **Award type:** 5
- **Project period:** 2019-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020753

## Citation

> US National Institutes of Health, RePORTER application 10020753, Hepatic protein-tyrosine phosphatase1B and alcoholic liver disease (5R21AA027633-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020753. Licensed CC0.

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