# Ceramide, AMPK, and YAP/TAZ Signaling in Hepatic Fibrogenesis

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $121,125

## Abstract

ABSTRACT
This is an application for an R03 Award by Dr. Jennifer Y. Chen, a hepatologist at the University of California,
San Francisco (UCSF). Dr. Chen's long-term career goal is to become an independently funded physician
scientist, devoting more than 75% of her time to establish and maintain a basic science research program in
hepatic fibrosis. Fibrosis is driven by activation of hepatic stellate cells (HSCs) and therapies to inactivate HSCs
have clinical potential as antifibrotic agents. The overall goal of Dr. Chen's research program is to develop novel
antifibrotic therapies for the clinical treatment of hepatic fibrosis. She has demonstrated that the sphingolipid
ceramide inactivates HSCs by inhibiting the YAP/TAZ signaling pathway. In this proposal, the candidate seeks
to elucidate how ceramide regulates upstream effectors of the YAP/TAZ pathway to inactivate HSCs and reduce
hepatic fibrogenesis. The applicant will utilize gain of function and loss of function approaches for the in vitro
studies. She will also perform co-immunoprecipitation experiments to determine the extent by which ceramide
modulates interactions with key regulators. For the in vivo studies, she will analyze conditional knockout mice
in a mouse model of fibrosis. A formal mentorship committee and advisory team will provide supervision,
guidance, and assistance for the candidate to achieve her goals. The research environment, which includes the
Division of Gastroenterology and the UCSF Liver Center, will provide a rich, collaborative, and supportive
atmosphere to ensure the candidate's success. The mechanistic understanding to be gained from the successful
completion of the proposed studies promises to reveal new nodes and targets for rational disease modification
in hepatic fibrosis, a disease with limited treatment options available. Completion of the studies will produce the
data and publication record necessary for a successful R01 application and significantly facilitate the transition
of the candidate to an independent physician-scientist.

## Key facts

- **NIH application ID:** 10352024
- **Project number:** 1R03DK131222-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer Y. Chen
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $121,125
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352024

## Citation

> US National Institutes of Health, RePORTER application 10352024, Ceramide, AMPK, and YAP/TAZ Signaling in Hepatic Fibrogenesis (1R03DK131222-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10352024. Licensed CC0.

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