Research Interests
The overall aim of the research carried out in our lab is to identify new anticancer drugs. To accomplish this aim, we use a wide range of experimental techniques ranging from organic synthesis to genetic screens. We also use a number of experimental systems including budding yeast and mammalian cell lines. A large part of our research involves drug screens. The largest screen we have carried out to date has been a two part screen in collaboration with the Developmental Therapeutics Program of the National Cancer Institute. We first screened FDA-approved anti-cancer drugs Part I. In part two, we screened over 100,000 compounds against a panel of yeast strains containing cancer-related genetic defects to identify compounds that may be selective in particular genetic contexts Part II . We identified over 100 compounds that target the bub3 mitotic checkpoint-deficient yeast strain (aneuploid cancer cell model).
Other projects have included screens for inhibitors of the Sir2 transcriptional repressor (important for aging and cancer) and the c-myc oncogene (relevant to many forms of cancer). We have also worked to develop new methods for drug target identification. Most of the projects can be described as applications of chemical genetics, meaning that we use small molecule modulators of enzyme activity to phenocopy mutants. This approach allows us to use classic genetics techniques to identify drug targets or, conversely, to identify drug targets based on similarities in phenotypes of drug-treated wild-type cells and mutants.
Lab Members
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