The focus of the Fungal Genomics Group is the study of how fungal pathogens evolve to cause disease. Fungi are a leading cause of mortality, yet are understudied compared to other microbes that cause infection. We examine how pathogen genetic variation and associated phenotypes contribute to virulence and to antifungal drug resistance. The group utilizes comparative and population genomic approaches to trace variation so as to understand how pathogens evolve within the course of single infection, across outbreaks, at global population scales, and between species. We collaborate widely within the Broad Institute and with research and clinical groups around the world.
Candida auris emergence and drug resistance
The global emergence of Candida auris represents a major new threat due to high levels of drug resistance, often to multiple classes of antifungal drugs. By comparing genomes of Candida auris isolates from around the world, our work is revealing the phylogeography and timing of clade expansions, and identifying unique properties of the genetic clades of this species, such as the genomic instability of clade II isolates.
Candida albicans genomic variation
Candida albicans is commonly found in the microbiome of healthy individuals, and is a frequent cause of bloodstream infections. We are interested in characterizing 1) how variation between diverse strains is linked to host phenotypes, and 2) the microevolutionary changes that occur when the immune system or antifungal drugs fail to clear a single infecting strain.
Evolution of the Cryptococcus species complex
Cryptococcus is a major cause of environmentally-acquired fungal infections. Individual Cryptococcus isolates vary in how they interact with the host and cause disease. By comparing fungal genomes from large sets of clinical and environmental isolates, we are identifying variants associated with clinical and in vitro phenotypes, characterizing the global population structure of Cryptococcus, studying how microevolution can reveal genes involved in host adaptation, and cataloging how expression varies across distinct genetic lineages.
Several species of “dimorphic fungi” are endemic to particular regions of the world and cause severe infections. We have characterized genomic variation or gene expression during infection in Blastomyces, Histoplasma, Paracoccidioides, Talaromyces, and the new genus Emergomyces, and studied how these species differ from related saprobic fungi.
Antifungal drug resistance
The treatment of fungal infections is compounded by rising antifungal resistance. A 2019 CDC report on antimicrobial threats included for the first time included a fungal species, Candida auris, among the five most urgent antimicrobial threats. The same report listed with other Candida species as serious threats, and included azole-resistant Aspergillus fumigatus on a watch list. Our goal is to identify genomic changes that confer antifungal resistance across populations of clinical isolates, and to study the impact of these mutations on fitness.
Rapid and accurate diagnosis of clinical fungal infections is a major challenge in patient care. In collaboration with the Bhattacharyya lab, we are working to adapt an RNA-based method for diagnosing bacterial infections for use in identifying fungal species in clinical specimens, and in parallel to develop RNA signatures for typing antifungal resistance.