# Signal sensing, hyphal development and pathogenesis of Candida albicans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $438,041

## Abstract

Candida albicans is one of the most frequently isolated fungal pathogens of humans. It is
a permanent resident of the healthy gastrointestinal microbiome, existing mostly as the
yeast form. But when host immunity is impaired, disseminated C. albicans infections can
occur with a high mortality rate. A critical virulence attribute of C. albicans is its
morphogenetic plasticity. In response to host environmental cues, this fungus can grow
as yeast, pseudohyphal, and hyphal forms. Mutants that are defective in hyphal
formation display attenuated virulence in animal models of systemic candidiasis. Our
long-term goal is to understand the signaling pathways that govern C. albicans
morphogenesis. Recent studies from our laboratory show that hyphal development
consists of two temporally linked phases, initiation and maintenance. Initiation requires
the Ras-cAMP-protein kinase A (PKA) pathway that regulates the rapid but temporary
disappearance of the Nrg1 transcriptional repressor of hyphal development.
Maintenance requires the Brg1 transcription factor-mediated promoter chromatin
remodeling of hypha-specific genes in response to nutrient limitation in air or stabilization
of the Ume6 transcriptional activator under hypoxia and hypercapnia. Aim 1 will
characterize the C. albicans hyphal initiation pathways that are essential for systemic
infection. We will study how C. albicans cells integrate signals from N-
acetylglucosamine, amino acids and pH to control hyphal initiation programs. Aim 2 will
use mutant screens and genetic analysis to uncover signaling pathways that sense
hypoxia, high CO2, and iron depletion to sustain hyphal elongation in systemic infection.
This proposal will gain molecular insights into how host signals are sensed by C.
albicans to control hyphal development during infection, which is critically important in
understanding its pathogenicity. The results of these in-depth investigations will provide
new insight into the mechanisms that govern hyphal initiation and maintenance in an
important fungal pathogen, and will serve as the foundation for novel therapeutic
strategies against C. albicans. Furthermore, the signaling pathways to be examined in
this application are likely conserved among diverse fungal pathogens. Data from these
studies will provide insight into signaling pathways that govern virulence in other fungi.

## Key facts

- **NIH application ID:** 9849775
- **Project number:** 5R01GM117111-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Haoping Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,041
- **Award type:** 5
- **Project period:** 2017-02-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849775

## Citation

> US National Institutes of Health, RePORTER application 9849775, Signal sensing, hyphal development and pathogenesis of Candida albicans (5R01GM117111-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849775. Licensed CC0.

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