# Stress-induced cell death mechanisms of fungi

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $204,688

## Abstract

PROJECT SUMMARY
Molecular cell death pathways are being extensively studied in mammalian cells. These genetically regulated
cell death processes are critical for maintenance of human health, defense against infection and for successful
cancer therapy, but their deregulation underlies disease pathology. Considerable progress towards delineating
the molecular details has yielded successful designer drugs now entering the clinic, such as venetoclax that
specifically targets anti-apoptotic BCL2 to trigger tumor cell death. In contrast, analogous approaches are not
available for triggering intrinsic cell death pathways encoded by human pathogens such as fungi, bacteria and
parasites because very little is known about the basic biology. The near complete lack of understanding of the
relevant events in dying microbial cells is surprising given their importance as human pathogens. For example,
fungal pathogens pose an increasing threat to public health, claiming 1.5 million lives annually worldwide. The
long-standing assumption that microbial cells do not encode such intrinsic death pathways has delayed
advancements in this direction. However, new rigorous evidence from multiple sources argues strongly in
favor, and partially delineated death pathways in multi-cellular fungi provide additional compelling support.
Here we propose to map the first molecularly defined death pathway in a single-cell fungal/yeast species, the
laboratory workhorse Saccharomyces cerevisiae (Aim 1), and to initiate studies that extend this knowledge to a
single-cell human fungal/yeast pathogen Cryptococcus neoformans, a major public health burden (Aim 2).

## Key facts

- **NIH application ID:** 10077258
- **Project number:** 5R21AI144373-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** J. Marie Hardwick
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $204,688
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077258

## Citation

> US National Institutes of Health, RePORTER application 10077258, Stress-induced cell death mechanisms of fungi (5R21AI144373-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077258. Licensed CC0.

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