# Dissecting the Role of Podxl in Hepatic Stellate Cells in Liver Development and Regeneration

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $29,520

## Abstract

PROJECT SUMMARY/ABSTRACT
 The mechanisms that control hepatic stellate cell (HSC) migration during liver development and
regeneration are not well understood. This knowledge gap has hindered the generation of new therapies and
the improvement of patient outcome for various developmental disorders such as congenital hepatic fibrosis and
fibrosing liver diseases such as alcoholic and non-alcoholic steatohepatitis. The critical need addressed in this
proposal is to identify and characterize factors that influence HSC migration during development and in
regeneration. HSCs migrate to the liver from the septum transversum early in vertebrate development. Once in
the liver, HSCs secrete growth factors and cytokines, such as TGF-ß and FGF10, that promote hepatocyte
proliferation. In the healthy adult liver, HSCs’ main function is to act as a storage site for vitamin A and regulate
extracellular matrix (ECM) turnover. When the liver is injured, HSCs migrate to the liver injury site where they
secrete ECM, growth factors, and cytokines to promote liver regeneration. Little is known about the factors
involved in HSC migration into the liver during development and throughout the liver in response to injury. My
long-term goal is to define mechanisms of liver development and regeneration, providing a foundation for
improved therapies and patient outcomes for congenital disorders and fibrotic liver diseases. The overall
objective of this proposal is to define mechanisms that control HSC behavior during development and
regeneration. The central hypothesis in this proposal is that podxl regulates HSC migration to the liver during
normal development (Aim 1), and within the liver in response to injury (Aim 2). Podxl is a highly sialylated and
glycosylated transmembrane protein that is known to promote migration of several cell types, including
hematopoietic stem cells and cancer cells. Several studies have shown that podxl is highly expressed in
zebrafish HSCs, and our preliminary data demonstrates that knockdown of podxl in zebrafish during
development results in fewer HSCs in the liver. In this study, the aim is to determine the role of podxl in HSCs
during development and regeneration. A podxl mutant and overexpression line will be created to determine the
role and mechanism of podxl in development. The working hypothesis is that Podxl promotes HSC migration by
interaction of its DTHL motif with the actin-binding protein Moesin. In addition, homologous recombination will
be used to create an HSC-specific Cre line that can be used to knock down genes in HSCs. This new HSC
expressing Cre line will be used to knock down podxl in HSCs and determine how that influences their migration
to liver injury sites and subsequent hepatocyte proliferation. This project involves generating novel genetic and
imaging tools, which will be instrumental for my career development. Understanding the role of podxl in HSC
migration during development and regeneration is significant beca...

## Key facts

- **NIH application ID:** 10069076
- **Project number:** 1F31DK124991-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Alexis Noel Ross
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $29,520
- **Award type:** 1
- **Project period:** 2020-07-08 → 2023-07-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069076

## Citation

> US National Institutes of Health, RePORTER application 10069076, Dissecting the Role of Podxl in Hepatic Stellate Cells in Liver Development and Regeneration (1F31DK124991-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10069076. Licensed CC0.

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