P. David Rogers Lab

Candida albicans is the most common fungal pathogen in man. In recent decades resistance to front-line antifungal therapy has emerged, particularly in immunocompromised patient populations. Through a long-standing collaboration with investigators at the University of Würzburg, Swansea University, and the University of Missouri – Kansas City, we are dissecting the molecular mechanisms of antifungal resistance in C. albicans to improve the treatment of infections due to this yeast and using it as a model to understand antifungal resistance in other fungal pathogens.  

Candida glabrata is a fungal species found commonly in patients with systemic infections in the ICU and is inherently resistant to one of the existing classes of anti-fungal agents. To understand how we might improve clinical treatment, through a collaborative effort with investigators at the University of Iowa, we are dissecting the pathways essential for resistance and determining whether they are drug targetable. It is our hope to reclaim a whole class of agents by defining, and manipulating, these mechanisms.

Candida auris has recently been classified by the CDC as an urgent antibiotic resistant public health threat. There are examples of single- and multi-drug resistance within this species, making it a significant clinical challenge. In a collaborative effort between St. Jude, the Broad Institute, and the CDC, our team is working to uncover the genetic and molecular mechanisms of resistance. The emergence of this pathogen aligns with advances in technology and access to clinical isolates. This has facilitated large scale profiling of whole genome sequencing data and application of CRISPR/Cas9 approaches for refined gene editing in previously intractable models.

Aspergillus fumigatus is one of the most common aspergillus species to cause disease in immune-compromised individuals. It also demonstrates emerging resistance to an historically superior class of antifungal agents. While overexpression of efflux pump and mutations in the gene encoding the drug target contribute to resistance, much of the antifungal resistance of A. fumigatus remains unexplained. Using whole genome sequencing of clinical isolates, we are working closely in collaboration with investigators at the Broad Institute and the Universty of Tennessee Health Science Center to understand the molecular mechanisms of resistance more thoroughly and hopefully develop new therapeutic approaches.