I'm studying mechanisms that maintain genomic stability in S. cerevisiae. In particular, I'm analyzing how disruption of the topoisomerases Top1 and Top2 (by both mutation and by drug inhibition) induces mitotic DNA recombination. Top1 and Top2 are, respectively, important for transcription and chromosome segregation. These studies will give insights into how topoisomerase function is important for maintaining stable DNA during these processes. The drug studies are particularly interesting from a clinical viewpoint, as topoisomerase inhibitors are frequently used as chemotherapeutics, and this may be relevant to understanding the genome changes that result in chemotherapy-induced secondary cancers. I'm using high-throughput sequencing and SNP microarrays to fine map and characterize the recombination events. The project will also be extended into mammalian cells on a limited basis.
Genome instability is associated with diseases such as cancer, and consequently studying the causes and effects of genome instability is important to human health. I am studying DNA topoisomerases, which are linked to both the induction of genome instability as well as protection from genome instability.