Our general approach is to develop and apply genetic and biochemical methodologies in the model organism, Saccharomyces cerevisiae (bakers yeast), to obtain an understanding of molecular components required for chromosome transmission, with the overarching goal of relating our work in yeast to human cancer. We have established an extensive genome instability gene catalog in yeast that provides a resource to identify cross species, candidate human genes that are somatically mutated and could cause chromosome instability (CIN) in cancer. Our functional studies of selected CIN genes in yeast have elucidated mechanistic insights into various aspects of the chromosome cycle, including sister chromatid cohesion, kinetochores, DNA replication and repair, and cell cycle checkpoints. We have also developed a strategy to identify genes in yeast synthetic lethal (SL) interaction networks as a means for identifying novel cancer drug targets. Our research involves a direct path from identification and mechanistic studies of CIN genes in yeast, to mining sequence data for orthologs mutated in cancer, to interrogation of the function of somatic variants and finally the identification of (1) therapeutic target genes defined by synthetic lethality and (2) small-molecule inhibitors of those targets.
Lab website: http://www.msl.ubc.ca/faculty/hieter