Research Overview

My research group integrates fungal systems biology with single-cell imaging, multi-omics analysis, and artificial intelligence (The Innovation 2024, last corresponding author) to address fundamental questions in medical mycology. Our major discoveries include:

1) Cell-density-driven sexual reproduction in pathogenic fungi: We demonstrated that quorum sensing governs sexual reproduction in Cryptococcus neoformans, providing the first evidence that microbial quorum sensing molecule can drive eukaryotic-specific behaviors, sexual reproduction and meiosis (Nature Microbiology 2018, independent corresponding author, Hero Image; Annual Review of Microbiology 2021, independent corresponding author).

2) Spatiotemporal regulatory landscape of fungal reproductive strategies: We systematically mapped the molecular networks controlling different modes of reproduction in Cryptococcus deneoformans (Nature Communications 2022, independent corresponding author, Featured Article).

3) Host-induced phenotypic antifungal resistance: We developed the field of host-driven antifungal tolerance and persistence, showing that host microenvironments critically influence drug efficacy during fungal infections (Nature Microbiology 2024a, independent corresponding author, Featured Article).

4) Discovery of a multidrug-resistant emerging fungal pathogen: We identified Rhodosporidiobolus fluvialis as a novel human pathogen capable of pan-resistance and hypervirulence, with mammalian body temperature acting as a mutagenic driver (Nature Microbiology2024b, last corresponding author, Featured Article).

5) Development of effective antifungal strategies: We discovered that the combination of an inositol phosphorylceramide synthase inhibitor with amphotericin B achieves significantly better cure rates in fungal meningitis than the current clinical standard. Using drug repurposing, we identified the first FDA-approved drug with activity against antifungal persisters (Cell Host & Microbe 2024, last corresponding author, Featured Article) and another FDA drug active against pan-resistant fungal strains.