Research Interests

Understanding how eukaryotic pathogens generate genetic and phenotypic variation at both the cellular and population levels as a response to antifungal drugs and environmental stresses and has meaningful clinical and evolutionary implications. We investigate the genome plasticity and acquisition of antifungal drug resistance in the yeast Candida albicans, a commensal that primarily resides in human gastrointestinal tracts and causes superficial infection in healthy individuals and serious infection in immunocompromised individuals. In particular, we examine how shifts in ploidy, mediated by sexual cycles in addition to asexual mechanisms promote genetic diversity within a population of cells. These ploidy transitions facilitate large-scale mutations including recombination, aneuploidy and homozygosis of whole chromosomes within a single cell division and fuel rapid adaptation. The Hickman lab employs traditional genetics, experimental evolution, molecular and cellular biology approaches along with high throughput tools to analyze individual cells within a population under a variety of environmental conditions.

The Candida albicans lifecycle

Ca lifecycleCandida albicans, was considered to be an ‘obligate’ diploid organism for nearly a century with no viable haploid stage until recently (Hickman et al 2013). Unlike other budding yeasts, C. albicans does not go through meiosis to reduce ploidy, but rather utilizes stochastic and imprecise concerted chromosome loss processes that frequently result in a heterogeneous population as some cells will have chromosomal aneuploidy and/or homozygosis.

Experimental comparative genetics

 hemiascomycete phylogeny

We also utilize experimental comparative genetics by using well-established model and non-model yeasts that display a wide-range of sexual, morphological, ecological and pathogenic lifestyles, yet maintain high levels of genome conservation in order to understand microbial population dynamics as well as the molecular mechanisms by which genome changes arise and their subsequent consequences on fitness.