Cullen is interested in using mathematics to study biology. As an undergraduate he studied attention and schizophrenia. Currently his work centers around studying the genetic variation that governs phenotypic variation in the budding yeast, Saccharomyces cerevisiae and also pathogenic yeasts, such as Cryptococcus neoformans and its relative Cryptococcus deneoformans. Cryptococcus species are estimated to affect a little under a quarter of a million individuals, causing approximately 180,000 mortalities every year. Phenotypic traits necessary for pathogenesis have been identified in Cryptococcus, such as the ability to grow at the human body temperature. However, little is still known as to why Cryptococcus species and strains vary in their ability to be pathogenic, ranging between benign to hyper-virulent. His work focuses on using mathematical, statistical, and computational approaches, such as quantitative trait locus mapping, to elucidate the genetic architecture underlying variation in phenotypes liked to virulence, including high temperature tolerance and drug resistance. Ultimately, he aims to understand the global distribution of alleles associated with hyper-virulence.