# Regulation of Candida albicans Pathogenesis by Protein Kinase and Transcription Factor Networks

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $751,293

## Abstract

PROJECT SUMMARY
Candida albicans is both a component of the human mycobiome as well as one of the most important human
fungal pathogens, capable of causing disease in both immunocompetent and immunocompromised people.
The pathogenic cycle that leads to invasive C. albicans disease can be divided into three steps: 1) transition
from mucosal colonization to sub-epithelial invasion; 2) filamentous morphogenesis within the sub-epithelium
leading to tissue damage; and 3) intravascular dissemination to target organs. Infections that stop after the first
two steps lead to mucosal diseases such as oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis
while those that progress to the third step cause life-threating candidemia and deep organ disease. Although
all three steps are required for the development of invasive disease, the third has been the most extensively
studied through the widely used tail-vein inoculation mouse model of disseminated infection. In this application,
we propose to use our barcoded collections of transcription factor (TF) and protein kinase (PK) mutants in
competitive fitness assays to genetically define the global regulatory networks and key downstream effectors
required for OPC mucosal infection (Aim 1). This aim will be facilitated by our recent development of an in vivo
RNA-seq approach to characterize the transcriptional profile of C. albicans during OPC. In Aim 2, we will
characterize the functions of the TF networks and identify the upstream PK signaling pathways that regulate in
vivo filamentation. We will identify PK substrates critical for in vivo filament initiation and elongation. The
successful execution of these aims will provide an unprecedentedly detailed in vivo profile of the regulatory
mechanisms for the first two steps in C. albicans pathogenesis. Since PKs have emerged as important
therapeutic targets across multiple areas of medicine, identification of PK networks with critical roles in C.
albicans pathogenesis also holds promise to provide new insights with relevance to antifungal drug
development.

## Key facts

- **NIH application ID:** 10875879
- **Project number:** 1R01AI177254-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Scott G Filler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $751,293
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875879

## Citation

> US National Institutes of Health, RePORTER application 10875879, Regulation of Candida albicans Pathogenesis by Protein Kinase and Transcription Factor Networks (1R01AI177254-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10875879. Licensed CC0.

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