Program Faculty

Research in my laboratory focuses on mechanisms that control genome stability through activation of cell cycle checkpoints and maintenance of chromosome segregation. I first reported the identification of the protein kinase Chk1 in 1993 and described its DNA damage-induced phosphorylation in 1996. Building on those studies, work in my laboratory has revealed mechanistic insight on the role of Chk1 in delaying cell cycle progression in the presence of DNA damaging agents including radiation and drugs used in cancer chemotherapy. While studies in my lab have been carried out in the model eukaryote, Schizosaccharomyces pombe, work by others revealed that Chk1 function is conserved in all eukaryotic cells. Because inhibition of Chk1 by mutation (in yeast) or with small molecule inhibitors (in mammalian cells) sensitizes cells to killing by DNA damaging agents, clinical studies have addressed whether Chk1 inhibitors in combination with known DNA damaging agents would be effective in cancer therapy. My laboratory makes use of cell biology, cellular biochemistry and genetic approaches to evaluate pathways with which the Chk1-dependent checkpoint pathway interacts. We identified Msc1, related to the KDM5 family of proteins in mammalian cells, as a dosage suppressor of a chk1 mutant and have described a role for Msc1 in maintaining chromosome stability. Our studies, informed by additional work by others on the roles of mammalian homologues of Msc1, lead us to speculate that Msc1 acts through nucleosome regulatory pathways to foster stability of kinetochore attachments to the mitotic spindle. Ongoing work in the laboratory focuses on the role of Chk1 in drug resistance and of Msc1 in genome stability.

Publications

NCBI Bibliography