# Microbe dependent mechanisms that antagonize intestinal injury repair

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY
Debaryomyces hansenii is a fungal member of the gut microbiome and is present within inflamed regions of the
intestine in Crohn Disease patients. Patient-derived strains of D. hansenii prolong wound healing in mouse
chemical and mechanical intestinal injury models. Mechanisms of pathogenicity of D. hansenii are not well
understood, though macrophages are a key effector cell type in the delayed wound healing phenotype. The
objective of the proposed work is to define mechanisms of innate host response to D. hansenii using in
vitro macrophage models and define microbial mechanisms of impaired wound repair using in vivo
models of intestinal injury. Our preliminary data visualizing phagocytosed D. hansenii with transmission
electron microscopy and cytological staining demonstrate certain macrophages phagocytose and are unable to
clear D. hansenii. Macrophages that do not clear D. hansenii also do not produce TNF-α in response to D.
hansenii. In aim 1, I test the hypothesis that TNF-α supports macrophages clearance of phagocytosed D.
hansenii and identify the pattern recognition receptors responsible for TNF-α production. In aim 2, I examine
microbial morphologic-transitions as an immune evasion mechanism in vitro and in vivo. My preliminary data
suggest that vegetative D. hansenii yeast induce more potent pro-inflammatory cytokine production than spores
of D. hansenii, and spores persist within macrophage cell lines in vitro. This project will define microbial
mechanisms that permit D. hansenii persistence within the intestine and antagonism of injury repair. Successful
completion of these aims will define mechanisms of host-response to D. hansenii and microbial-evasion of
macrophage clearance that will lead the identification of novel therapeutic targets for treating the subset of Crohn
Disease patients with tissue associated D. hansenii.

## Key facts

- **NIH application ID:** 10852853
- **Project number:** 5F30DK138707-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Kevin Prescott Newhall
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852853

## Citation

> US National Institutes of Health, RePORTER application 10852853, Microbe dependent mechanisms that antagonize intestinal injury repair (5F30DK138707-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10852853. Licensed CC0.

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