# SET Domain Epigenetic Factors Govern Antifungal Drug Efficacy and Fungal Pathogenesis

> **NIH NIH R01** · PURDUE UNIVERSITY · 2022 · $380,246

## Abstract

Project Summary/Abstract:
In recent years, a significant increase in mortality of patients with microbial fungal infections has been
observed. This is primarily due to a higher incidence of individuals who are immunocompromised
including HIV-infected patients, patients undergoing cancer therapy, organ transplant recipients, and
patients with advanced stages of diabetes. A complication in treating patients with fungal infections is
the development of multidrug-resistant fungi. With the limited number of effective antifungal drugs, the
increase of drug resistant fungi, and development of new pathogenic fungi, fungal infections are a
major threat to human health. The proposed studies help to solve this issue by identifying underlying
causes for drug resistance and to identify additional molecular targets for development of new
antifungal drugs that will effectively treat fungal infections or work in combination with current
treatments. Our central hypothesis is that SET domain epigenetic factors regulate genes or pathways
that alter antifungal drug resistance. This hypothesis was established based on our preliminary
observations showing that loss of SET domain coding genes such as SET1, SET3, and SET4 can
alter the efficacy of antifungal drugs. This proposal will use S. cerevisiae, the opportunistic pathogen,
C. glabrata, and G. mellonella larvae as model systems to identify key epigenetic regulators and to
study the impact of epigenetics and epigenetic factors on antifungal drug resistance and pathogenicity.
The epigenetic mechanisms that regulate the expression of genes and pathways important for
antifungal drug resistance will be identified, a new precursor sterol pathway will be characterized, and
the biological and biochemical function of the newly defined epigenetic factor, Set4 will be determined.
Overall, studying SET domain proteins and other epigenetic factors will have a positive impact on
public health by providing fundamental new insights in the areas of fungal infections and antifungal
drug resistance.

## Key facts

- **NIH application ID:** 10462528
- **Project number:** 5R01AI136995-05
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** SCOTT D BRIGGS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,246
- **Award type:** 5
- **Project period:** 2018-09-24 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462528

## Citation

> US National Institutes of Health, RePORTER application 10462528, SET Domain Epigenetic Factors Govern Antifungal Drug Efficacy and Fungal Pathogenesis (5R01AI136995-05). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10462528. Licensed CC0.

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