# Signal sensing, hyphal development and pathognesis of Candida albicans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $480,280

## Abstract

PROJECT SUMMARY
Candida albicans is one of the most frequently isolated fungal pathogens of humans. 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. 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. We have uncovered conserved sensors for N-actylglucosamine (GlcNAc),
CO2, and hypoxia that are linked to hyphal development. In the current proposal, we will
extend these studies through the following aims: Aim 1. Investigate Nrg1 down-
regulation during hyphal initiation. Aim 2. Examine signaling pathways for hyphal
morphogenesis inside macrophage. Aim 3. Identify transcriptional programs under
hypoxia and physiological CO2. 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:** 10596976
- **Project number:** 5R01GM117111-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Haoping Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $480,280
- **Award type:** 5
- **Project period:** 2017-02-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596976

## Citation

> US National Institutes of Health, RePORTER application 10596976, Signal sensing, hyphal development and pathognesis of Candida albicans (5R01GM117111-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10596976. Licensed CC0.

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