What we work on

Genomic technology development 

CRISPR-based genomic tools for the manipulation of genetically-intractable microorganisms
To better study the biology and virulence of fungal pathogens, we are developing new genomic technology platforms for diverse fungal species. We are exploiting CRISPR-Cas9 based technologies to revolutionize the way we do high-throughput functional genomic analysis in fungal pathogens. This is enabling us to map genetic interactions, and uncover genetic factors and pathways that mediate important phenotypes associated with pathogenesis, antifungal drug resistance, and other biological processes.

Relevant publications:

• ​ A CRISPR interference system for efficient genetic repression in Candida albicans
• ​Design, execution, and analysis of CRISPR-Cas9-based deletions and genetic interaction networks in the fungal pathogen Candida albicans
  
• CRISPR-based genomic tools for the manipulation of genetically-intractable microorganisms
• A CRISPR-Cas9-based gene drive platform for genetic interaction analysis in Candida albicans
• Precise Cas9 targeting enables genomic mutation prevention

Fungal pathogenesis

We are interested in microbial fungal pathogens, and the mechanisms by which they cause disease. Most of our work focuses on the human fungal pathogen Candida albicans, but we are also expanding our research to include other fungal pathogens of both humans and plants. We use genetics and systems-level analysis to assess cellular factors involved in fungal pathogenesis and virulence pathways - including cellular morphogenesis and biofilm formation. 

​Relevant publications:

• Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans​
• ​​Linking cellular morphogenesis with antifungal treatment and susceptibility in Candida pathogens
• New pathogens, new tricks: emerging, drug-resistant fungal pathogens and future prospects for antifungal therapeutics
• ​​Global gene deletion analysis exploring yeast filamentous growth
• The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug resistance
• Pho85, Pcl1, and Hms1 signaling governs Candida albicans morphogenesis induced by high temperature or Hsp90 compromise
• Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression in Candida albicans
• Mapping the Hsp90 genetic interaction network in Candida albicans reveals environmental contingency and rewired circuitry
• Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling

Antifungal drug resistance

Resistance to antifungal drugs is a serious clinical concern. We study the mechanisms by which fungal pathogens evolve antifungal drug resistance, and identify genetic factors involved in mediating this resistance. Using experimental evolution, molecular genetic techniques, and whole genome sequencing analysis, we are building an understanding of how fungi evolve resistance to diverse classes of antifungal agents.

Relevant publications:

• FDA approved drug library screening identifies robenidine as a repositionable antifungal
  
• Linking cellular morphogenesis with antifungal treatment and susceptibility in Candida pathogens
• New pathogens, new tricks: emerging, drug-resistant fungal pathogens and future prospects for antifungal therapeutics
• A role for the bacterial GATC methylome in antibiotic stress survival
• Antimicrobial-induced DNA damage and genomic instability in microbial pathogens
• The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug resistance​