# Defining a novel mechanism of mucosal healing

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $499,508

## Abstract

PROJECT ABSTRACT
Chronic inflammatory diseases, such as inflammatory bowel disease (IBD), are a significant socio-economic
problem with an accelerating incidence around the world that affects adolescents and young adults. These
diseases manifest with chronic dysregulated immune responses that ultimately promote tissue destruction.
While most current therapeutic approaches are focused on limiting inflammation, there is an urgent need to
develop novel strategies that also facilitate tissue repair and mucosal healing. The fundamental focus of this
research proposal is to mechanistically define a novel pathway that promotes mucosal healing in the
intestine, and further determine its therapeutic potential in preclinical mouse models. In our preliminary
data, we unexpectedly identified that hepcidin, the master regulator of systemic iron homeostasis in mammals,
is an essential promoter of mucosal healing in the intestine. Surprisingly, hepatocytes were not the critical
cellular source of hepcidin in this context, but rather we identified that dendritic cells (DCs) express hepcidin in
response to microbial simulation. Further, we identified that DC-derived hepcidin support mucosal healing by
regulating local iron levels and modulating the composition of the intestinal microbiota. These findings
provoke the central hypothesis that DC-derived hepcidin is a critical regulator of mucosal healing. We
will employ theses approaches and develop innovative tools to define the role and regulation of DC-derived
hepcidin during homeostasis or following intestinal damage and inflammation. Three specific aims of this
project will determine (i) What DCs express hepcidin and how is DC-derived hepcidin regulated to promote
mucosal healing? (ii) How does DC-derived hepcidin mechanistically influence mucosal healing? and (iii) Can
hepcidin be therapeutically harnessed to support mucosal healing? Collectively, these studies will
mechanistically define the role and regulation of DC-derived hepcidin in basic mouse models and human
samples. Further, the proposed studies will provide important pre-clinical evidence on the therapeutic potential
of modulating DCs or hepcidin in the context of IBD and other chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 9858258
- **Project number:** 5R01AI143842-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Gregory F Sonnenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $499,508
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858258

## Citation

> US National Institutes of Health, RePORTER application 9858258, Defining a novel mechanism of mucosal healing (5R01AI143842-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858258. Licensed CC0.

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