# Epidermal Growth Factor Receptor Signaling in Fibrotic Skin Disease

> **NIH NIH K08** · YALE UNIVERSITY · 2021 · $172,260

## Abstract

PROJECT SUMMARY/ABSTRACT
Fibrosis is a common final outcome of most human chronic inflammatory diseases and has been estimated to
contribute to almost half of all deaths in the world 1. It can result from autoimmune diseases such as scleroderma,
after stem cell transplant in graft-vs-host disease, from chronic inflammatory conditions associated with obesity
and diabetes and through inherited genetic disorders. Fibrosis can affect virtually any organ including the skin,
lungs, kidneys, liver, heart and blood vessels. Scleroderma and graft-vs-host disease most commonly affect the
skin and the degree of skin involvement is associated with higher mortality and internal organ dysfunction 2,3,
suggesting common underlying mechanisms. We previously identified in these diseases activation of epidermal
growth factor receptor (EGFR) on fibroblasts by its immune cell derived ligand epiregulin. This proposal aims to
further elucidate the major gaps in our knowledge of how EGFR signaling drives fibrosis in the skin. In particular,
it is unclear what signaling pathways downstream of EGFR activation are critical to different phases of fibrosis
and how these targets cross-talk with other fibrosis-associated pathways.
In this project, we examine the cellular signals that result from chronic EGFR activation in fibroblasts and
pericytes and their cross-talk with STAT1, an essential transcription factor for regulating interferon-dependent
gene expression. In our first aim, we will characterize the effects of EGFR activation in fibroblasts and pericytes
using a Tet-On expression system. This model system will allow temporal and cell-type control of EGFR
activation in vivo. We will analyze what EGFR pathways are activated and required for development of skin
fibrosis, and their effects on the immune system. In the second aim, we will examine the relevant cell types in
which STAT1 signaling is required for development of fibrosis using bone marrow chimeras and STAT1
conditional knockout mice. We will investigate whether EGFR and STAT1 signaling are co-dependent and utilize
proteomics techniques to discover protein interactions and modifications. Together, these aims will provide better
insight into the pathogenesis of fibrotic skin disease, lead to a broader understanding of fibrosis as a biological
process, and help develop new treatments that may substantially impact patients' lives.

## Key facts

- **NIH application ID:** 10214929
- **Project number:** 1K08AR077689-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Ian D Odell
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $172,260
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214929

## Citation

> US National Institutes of Health, RePORTER application 10214929, Epidermal Growth Factor Receptor Signaling in Fibrotic Skin Disease (1K08AR077689-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214929. Licensed CC0.

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