I am a chemical biologist and medical oncologist who specializes in the treatment of breast cancer. My career goal is to develop novel therapeutic strategies to treat breast cancer. I lead a research laboratory focused on using chemical biology to identify and validate mitotic protein kinases as breast cancer drug targets. My major research effort to date has focused on polo-like kinase 1 (Plk1), an essential protein kinase required for formation of mitotic spindles in dividing cells, cancer and non-cancer alike. I have developed a unique chemical-genetic system to study detailed function of Plk1 in human cells. This system allows chemical sensitivity to be genetically encoded so Plk1 can function can be interrogated with high temporal precision and genetic controls to ensure against off-target effects. Using this system, I was unable to uncover a novel function of Plk1 in late cell division and identify detailed mechanism. This approach can, in principle, be extended to any of ~500 kinases encoded in the human genome.
Our laboratory seeks to understand how protein kinases regulate human cell division and to use this knowledge to improve treatment of breast cancer. We have taken two approaches to the problem. First, we have used chemical genetics to identify function of protein kinases required for cell division, including Polo-like kinase 1. Chemical genetics overcomes the problem of specificity of kinase inhibitors and provide unique tools to identify functionally relevant kinase substrates. We are currently extending this system to other protein kinases involved in human cell division. Second, we identify unique characteristics of cancer cells (biomarkers) that make them susceptible to specific anticancer therapies. Our ultimate goal is to combine chemical genetics with biomarker analysis to develop validated kinase-targeted therapeutic approaches for all breast cancer types.