A postdoctoral position is available in the Laimins lab to study the life cycle of high-risk human papillomaviruses, which are the causative agents of most anogenital and many oral cancers. HPVs link their life cycles to epithelial differentiation and our work has identified many important mechanisms regulating viral pathogenesis. The Laimins laboratory was the first to use tissue culture methods to grow infectious high-risk HPV virions and to study the differentiation-dependent life cycle of high-risk HPVs. Recent work has demonstrated that HPVs activate the ATM and ATR DNA damage repair pathways and that this is critical for viral replication during the HPV life cycle. We recently demonstrated that HPV proteins induce high rates of DNA breaks in both cellular and viral DNAs. The breaks in viral genomes are rapidly repaired through the preferential recruitment of homologous recombination repair factors such as RAD51 and BRCA1 to episomes and away from cellular sites of damage. This preferential repair is necessary for genome amplification and late gene expression. The type II topoisomerase, TOP2, is responsible for generating over half of the DNA breaks in HPV positive cells and this is critical for activating DNA damage repair pathways along with viral replication. Ongoing projects will look at the roles of the topoisomerases in regulating DNA damage pathways as well as single cell analyses looking at factors regulating amplification. Additional project will examine changes in gene expression and epigenetic modifications associated with cancer progression using patient samples.