# Pr 4: Immune Responses to Fungi Associated with Crohn's Disease.

> **NIH NIH P01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $435,406

## Abstract

Abstract
Most studies of the microbiota and its role in inflammatory diseases in the intestines have focused on bacteria.
However, eukaryotes and viruses are also present and are likely to exert an impact on health and disease in the
gut. In previous studies, we have documented the complexity of the fungal community in the intestines of mice
and observed that effective host immunity to fungi is important in controlling inflammation in colitis models. In
preliminary data provided in this proposal, and conducted in collaboration with other members of this program
project grant (PPG), we document the complexity of the colonic mucosa-associated fungal community in humans
and observe significant differences in fungal communities found in patients with Crohn's Disease (CD).
The overall hypothesis of this proposal is that fungal communities in the gut affect and are affected by the immune
system and that these processes contribute to Crohn's disease.
In the first Aim, we will characterize in vitro immune responses to two fungi that are strongly associated with CD.
We will investigate the roles of Dectin-1 and CARD9 (two proteins in which genetic polymorphisms have been
linked to CD and/or Ulcerative Colitis) in immune sensing of these fungi. In the second Aim, we will investigate
the effects of these fungi on the makeup of the intestinal microbiome in mice, and determine the effects of these
fungi on the severity of disease in mouse models of colitis. In the third Aim, we will further define the presence
of these fungi in healthy people and in patients with CD, and in collaboration with other PPG members we will
identify associations between fungi and bacteria, metabolites, serology, and host genetics.

## Key facts

- **NIH application ID:** 10019375
- **Project number:** 5P01DK046763-28
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** David M. Underhill
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $435,406
- **Award type:** 5
- **Project period:** 1997-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019375

## Citation

> US National Institutes of Health, RePORTER application 10019375, Pr 4: Immune Responses to Fungi Associated with Crohn's Disease. (5P01DK046763-28). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019375. Licensed CC0.

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