# Functional characterization of CARD9 genetic variants in fungal immunity

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $698,281

## Abstract

ABSTRACT
Fungi are ubiquitous colonizers of skin and mucosal surfaces. While many individuals exhibit minor fungal
outgrowth, millions of others experience systemic infections with life-threatening consequences. Polymorphisms
in numerous genes have been associated with the ability of an individual to generate an inflammatory response
to fungal pathogens. In many of these genes, rare high-penetrance alleles have been observed that strongly
disrupt gene function, resulting in primary immunodeficiencies and an increase in infectious disease
susceptibility. Additionally, common genetic variants have been reported in these genes that increase the risk of
disease by modifying the activity or expression of the gene product to a small but significant degree. These
genes offer a unique opportunity to understand how immune responses to pathogens are tuned to achieve an
appropriate level of immune response. This hypothesis is well illustrated by the various phenotypes associated
with different genetic variants of CARD9. CARD9 is a signaling protein that functions downstream of many C-
type lectin receptors (CLRs), which recognize carbohydrate moieties on fungi and other pathogens.
Understanding how these human disease-related CARD9 mutations affect CARD9 functions will advance our
understanding of fungal immunity. In Aim 1 of this proposal, we examine the role of Card9 ubiquitination on
fungal detection by dendritic cells. In Aim 2, we will identify the molecular mechanisms controlling Card9
phosphorylation and their consequences for fungal detection. In Aim 3, we compare how Card9 genetic variants
affect Candida infection and the development of colitis. Together, these aims will decipher the mechanistic basis
of CARD9 regulation and characterize CARD9 genetic variants to identify novel molecular mechanisms with
important roles in fungal defense and inflammation.

## Key facts

- **NIH application ID:** 10087868
- **Project number:** 5R01AI137325-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ramnik J Xavier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $698,281
- **Award type:** 5
- **Project period:** 2018-02-08 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087868

## Citation

> US National Institutes of Health, RePORTER application 10087868, Functional characterization of CARD9 genetic variants in fungal immunity (5R01AI137325-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10087868. Licensed CC0.

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