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.
Chemical genetics in human cells
We use chemical genetic tools to reveal function of protein kinases involved in human cell division. The advantages of this approach include:
- Rapid inactivation of kinase function
- Reveals effect of chemical inhibition, which can differ from that of knockout/knockdown
- Includes explicit controls for specificity
- A single chemical can be used to reveal function of many kinases
Our goal is to develop a complete library of chemical genetic breast epithelial cell lines to explore synthetic lethal approaches to targeting breast cancer