Research Interests
Cryptococcus neoformans is a ubiquitously present human fungal pathogen that kills more than 180,000 people each year worldwide. While this fungus has been mainly associated with infections in immunocompromised people, infections in healthy individuals have been rising in recent years. A lack of basic understanding of this fungus and as well as an in-depth understanding of its virulence factors has made it challenging to identify new strategies to tackle and treat infections. My current research focuses on to better understand both evolutionary as well as pathogenic aspects of C. neoformans.
My research work recently led to the discovery of a novel reproduction mode in the form of pseudosexual reproduction. During this process, two cells of opposite sexes mate with each other but produce clonal progeny for only one of the parents, instead of recombinant progeny. We proposed that this mode allows this fungus to survive mating with incompatible partners in limiting and harsh conditions, and allows them to make hundreds of clonal spores for dissemination and spread. These spores are also the infectious propagules for C. neoformans and thus could also cause infections if they encounter a suitable host. We showed that pseudosexual reproduction occurs among natural isolates and our ongoing research shows that this could also happen between two species and is not limited to intra-species mating. I am currently working towards the identification of regulatory factors that might abolish or promote pseudosexual reproduction.
I am dissecting the details of calcium-calcineurin signaling in C. neoformans. Calcineurin signaling is responsible for thermotolerance, a key virulence factor in C. neoformans, and calcineurin mutants are completely avirulent in the mouse. Previous studies have identified a transcription factor Crz1 as one of the calcineurin targets that activates several genes in response to thermal stress. Using ChIP-seq on samples that were given variable time of thermal stress, I have identified targets whose promoters are bound by Crz1 either constitutively or transiently. I am now focussing on the characterization of the transcriptional regulatory pathway that governs thermotolerance in C. neoformans with calcineurin-Crz1 signaling playing a central role in it. In parallel, I have also developed a proximity-ligation approach, TurboID, for C. neoformans to understand the interactions of Calcineurin.