Professor Yue Wang obtained his Ph.D. from the Department of Genetics, Cell and Developmental Biology, the University of Minnesota, in 1988. He joined IMCB as a Postdoctoral Research Fellow in 1989 and was promoted to Principal Investigator in 1993 and Research Director in 2009. He joined A*ID Labs as a Senior Principal Investigator on 1 April 2022. For his outstanding research achievements, Professor Wang was awarded the President’s Science Award in 2012. He has served on Virulence, eLife, and Fungal Genetics and Biology editorial board.
Adjunct Professor, Department of Biochemistry, National University of Singapore. 2013-
Adjunct Associate Professor, Department of Microbiology, National University of Singapore. 2000-2012
Adjunct associate professor, National University Hospital, National University of Singapore. 2006-2008
Professor Wang’s scientific interests embrace the following areas:
(1) Mechanism of pathogenicity and virulence of fungal pathogens belonging to the Candida genus;
(2) Impact of the human microbiome on Candida infection;
(3) Role of microbiome-released peptidoglycan on host immunity.
Candida albicans is the most prevalent fungal pathogen in humans. Although it is a member of the human microbiota and generally harmless in healthy people, it can cause life-threatening invasive infections in immune-compromised people, with mortality often exceeding 40%. One well-characterized virulence trait of C. albicans is switching reversibly between the commensal yeast and the invasive hyphal states. One of our research focuses on identifying both host and fungal factors that promote the yeast-to-hyphal transition. Our key findings include the following. First, we identified microbiome-released peptidoglycan in human blood as a highly potent inducer of the hyphal growth of C. albicans (Cell Host & Microbe 4, 28). Peptidoglycan enters C. albicans’ cells and binds to the leucine-rich repeat of the adenylyl cyclase Cyr1 to activate cAMP synthesis, which triggers the Protein Kinase A signalling pathway, leading to hyphal growth. Second, we identified the HGC1 gene as a central regulator of the hyphal growth of C. albicans (EMBO J 23, 1845). HGC1 encodes a hyphae-specific G1 cyclin, forming a complex with the cell-cycle kinase Cdc28. We found that HGC1 is essential for hyphal growth, and its deletion abolishes virulence. So far, we have identified dozens of Hgc1/Cdc28 substrates, most of which are the central components of various cell polarity machines, leading to a comprehensive understanding of the molecular mechanisms governing the hyphal growth of C. albicans.
C. albicans is an obligate diploid yeast with a sexual cycle, rendering genome-wide genetic screens nearly impossible, significantly hampering C. albicans research and drug development. We constructed the first haploid strains of C. albicans via induced chromosome loss (Nature 494, 95). This achievement enables, first the first time, scientists to apply many genetic and molecular biology tools in C. albicans research. For example, we engineered the piggyBac transposon mutagenesis system in haploid C. albicans to conduct genome-wide searches for genes involved in antifungal resistance and discovered new mechanisms (Nature Communications 9, 4495; Nature Protocols 15, 2705).
Candida auris is a newly merged fungal pathogen. Since its first isolation in Japan in 2009, it has spread to >40 countries across six continents. C. auris is often called a ‘super bug’ because most clinical isolates are resistant to the first-line antifungal drug fluconazole. Many isolates are resistant to two, even all three classes of antifungal agents approved for treating invasive fungal diseases, causing hard-to-treat infections with high mortality. C. auris can also withstand harsh environmental conditions, including disinfectants commonly used to kill germs This results in its persistence and lateral transmission in hospitals and healthcare facilities. We introduced the piggyBac system into C. auris, performed a whole-genome genetic screen, and identified a global stress regulator, called DINOR, that governs drug resistance, stress response, and virulence (Nature Microbiology 6, 842). Our findings provide critical insights into potential new targets for developing antifungal therapeutics.
Endogenous signals regulating hyphal development in the principal fungal pathogen Candida albicans
Mapping the signaling pathways coupling mitochondrial functions with the invasive hyphal growth in the fungal pathogen Candida albicans
Elucidation of the mechanism of action of the global stress regulator, DINOR, in the super fungus Candida auris
Elucidation of antifungal resistance mechanisms in the emergent fungal pathogen Candida auris
PUBLICATIONSYue Wang (0000-0002-1211-2822) (orcid.org).