# Functional roles of ncRNA afu-182 in azole response and pathobiology of Aspergillus fumigatus

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2022 · $247,834

## Abstract

Project Summary:
Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a major cause of morbidity and
mortality in immune-compromised patients despite the availability of antifungal drugs. The global emergence of
azole drug resistance is a major factor contributing to poor disease outcomes; however, azole drug-resistant A.
fumigatus isolates contribute to only about 5% of infections. A major gap in knowledge is how azole sensitive
isolates tolerate azole drugs and contribute to poor disease outcomes with mortality rates in excess of 50%. To
this end, we have identified an uncharacterized long non-coding RNA (lncRNA) afu-182 that negatively
correlates with azole drug response and is a driver of azole drug tolerance in the laboratory and clinical
isolates. In this proposal, we will use genomics, genetics, biochemical approaches to define the mechanism of
afu-182 mediated azole drug tolerance in A. fumigatus. In specific Aim 1), we will define the pathways
regulating azole tolerance and afu-182 regulon to understand the molecular mechanisms involved in azole
tolerance. In Aim 2), we will define the afu-182 expression in vivo under azole stress in a murine model of
invasive pulmonary aspergillosis. Successful completion of proposed aims has tremendous potential to
improve clinical outcomes by defining mechanisms involved in azole tolerance and declassifying binary
resistant/susceptible spectrum for fungal isolates. This will help design better treatment strategies for azole
susceptible infections to achieve better disease outcomes.

## Key facts

- **NIH application ID:** 10494467
- **Project number:** 1P20GM146584-01
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Sourabh Dhingra
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,834
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10494467

## Citation

> US National Institutes of Health, RePORTER application 10494467, Functional roles of ncRNA afu-182 in azole response and pathobiology of Aspergillus fumigatus (1P20GM146584-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10494467. Licensed CC0.

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