# Copper homeostasis in fungal pathogenesis

> **NIH AI R01** · DUKE UNIVERSITY · 2026 · $482,071

## Abstract

SUMMARY
 Copper (Cu) is an essential trace element and a catalytic cofactor for a variety of enzymes
involved in cell growth, development, and stress resistance. Fungal systems have been
instrumental in identifying mechanisms of Cu utilization and homeostasis in diverse eukaryotic
cells. The experiments in this proposal will use a relevant fungal model system to explore Cu
homeostasis in microbial physiology and pathogenesis.
 Cryptococcus neoformans is an opportunistic fungal pathogen that is responsible for
>100,000 deaths annually, especially among patients with poorly treated HIV infection. This
pathogenic microorganism is an outstanding model to study rapid cellular adaptations between
high and low Cu states. This fungus has sophisticated transcriptional and post-transcriptional
Cu regulatory mechanisms to adapt to Cu overload and Cu limitation in biologically relevant
niches. C. neoformans first infects the host lung where it is engulfed by alveolar macrophages
and experiences toxic Cu bombardment within the phagolysosome. In immunocompromised
hosts, this fungus disseminates through the bloodstream to the central nervous system where it
causes lethal disease, and where it encounters extreme Cu starvation. Failure to acquire Cu, or
to adapt to low bioavailable brain Cu levels, results in defective fungal survival in the host.
Therefore, during the infection cycle this microorganism must be able to rapidly transition from a
Cu-resistant state during toxic Cu exposure to a Cu-foraging state during Cu limitation.
 The C. neoformans Cuf1 transcription factor is the primary regulator of the cellular response
to both high and low Cu levels. We and our prior collaborators therefore characterized the Cuf1-
dependent transcriptome and used this data to define conserved and novel mechanisms of
eukaryotic copper biology. These studies identified important cellular responses to Cu limitation
(increasing Cu import) as well as to Cu excess (inducing Cu detoxification process

## Key facts

- **NIH application ID:** 11292236
- **Project number:** 1R01AI184401-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** ANDREW  ALSPAUGH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $482,071
- **Award type:** 1
- **Project period:** 2026-02-19T00:00:00 → 2031-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11292236

## Citation

> US National Institutes of Health, RePORTER application 11292236, Copper homeostasis in fungal pathogenesis (1R01AI184401-01A1). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11292236. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*