# Investigating the function of macrophages in the efficacy of anti-fungal drugs in larval zebrafish

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2022 · $250,121

## Abstract

Project Summary/Abstract
Fungal pathogens cause life-threatening disease in immuno-compromised patients, with more than 2
million people affected world-wide each year. Anti-fungal drugs that are used in the clinic to treat
patients are ineffective, even though these drugs work well against fungi in a petri dish. The
overarching goal of the proposed research is to increase the efficacy of these drugs inside of
living organisms. The larval zebrafish is an ideal host in which to tackle this problem. Excellent live
imaging and genetic tools are available, the immune systems of zebrafish and humans are largely
conserved, and fungal infection models in zebrafish recapitulate pathogenesis in humans. Preliminary
data indicates that synergy between the anti-fungal drug voriconazole and macrophages in vivo
increases killing of the fungal pathogen Aspergillus fumigatus. I propose to identify genes and
pathways in macrophages that are modulated by azole treatment and that promote azole-mediated
fungal killing. First, I will focus on known cell biological pathways involved in pathogen recognition
and phagosomal killing, including pathogen recognition receptor (PRR) pathways, reactive oxygen
species (ROS) generation, and phagosomal acidification. Then, I will use an unbiased RNAseq-based
approach to identify unknown genes that are modulated by azole treatment. Hits from both of these
approaches could be targeted in the future for adjuvant therapy to boost anti-fungal efficacy in
infected hosts. Altogether, results from this proposal will identify new targets for immuno-
therapeutic adjuvant therapy to increase the efficacy of anti-fungal treatment in patients.

## Key facts

- **NIH application ID:** 10494468
- **Project number:** 1P20GM146584-01
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Emily Rosowski
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,121
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10494468

## Citation

> US National Institutes of Health, RePORTER application 10494468, Investigating the function of macrophages in the efficacy of anti-fungal drugs in larval zebrafish (1P20GM146584-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10494468. Licensed CC0.

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