# The role of liver progenitor cells in liver regeneration

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $653,664

## Abstract

Project Summary - The role of liver progenitor cells in liver regeneration
Acute and chronic liver disease causes liver failure and is a growing cause for morbidity and
mortality. The COVID-19 pandemic has further increased the magnitude of this problem. The liver
is a highly regenerative organ, yet the presence of a dedicated stem cell population remains
controversial. In our preliminary work, we describe a near-total hepatocyte ablation model in
zebrafish where organ regeneration is derived from biliary epithelial cells. Our objective here is to
characterize the functional implications and molecular mechanisms of EAE to affect organ
development. Our central hypothesis is that severe hepatocyte injury will reveal the facultative
stem cell potential of biliary epithelial cells. This process appears to be driven by EGFR, PI3K,
and mTOR signaling. Two Specific Aims are proposed to define the generation and contribution
of facultative hepatic stem cells. In Specific Aim 1 we will utilize single-cell transcriptomic and
high-resolution imaging analyses after near-total hepatocyte ablation to investigate whether and
when biliary epithelial cells undergo transcriptional and morphological changes to become
hepatocytes. In the process, we will generate an inventory of all liver cells in the zebrafish and
determine evolutionary conservation of cell identity and function by comparison to murine and
human liver datasets. Specific Aim2 will determine the degree of biliary epithelial cell proliferation
hepatoblast transcription factors gene expression prior to hepatocyte differentiation and define
the signaling pathways involved in the generation, function and proliferation of this facultative
stem cell population. Identification of a signal like EGFR that can cause biliary epithelial cells to
become hepatocytes has significant therapeutic potential for patients with liver failure.

## Key facts

- **NIH application ID:** 10775782
- **Project number:** 5R01DK135271-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Wolfram Goessling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $653,664
- **Award type:** 5
- **Project period:** 2023-02-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775782

## Citation

> US National Institutes of Health, RePORTER application 10775782, The role of liver progenitor cells in liver regeneration (5R01DK135271-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10775782. Licensed CC0.

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