Chemical Biology of Protein Kinases

Pharmacological approaches to studying kinases are attractive, however, these experiments require highly selective inhibitors. Unfortunately, few truly selective kinase inhibitors have been reported. My lab reported the first highly selective inhibitors for c-Src kinase, a kinase involved in many important and diverse oncogenic processes. Significantly, my lab has made each of our selective kinase inhibitors available free of charge. In addition, several of our inhibitors are commercially available. Our selective kinase inhibitors have made a large impact on the study of c-Src kinase in biological systems. 

Protein kinases play a key role in cell signaling and regulation of biological processes such as proliferation, differentiation, and apoptosis. More than 160 protein kinases have been implicated in disease, including cancer. In light of this, kinases are highly attractive targets for drug development. Despite the large number of potential targets, all clinically-used kinase inhibitors address only a handful of well-known kinases. My lab has developed methodologies that can be adapted to target any kinase of interest to generate inhibitors with high specificity. Our technologies enable identification of inhibitors for a wider breadth of kinase targets than existing strategies have yielded. 

Triple-negative breast cancer is an aggressive form of breast cancer for which there is no approved targeted therapy. My lab has explored the application of kinase inhibitors, especially inhibitors of c-Src kinase, in triple-negative breast cancer and we have elucidated signaling pathway changes resulting from inhibition of key kinases. In addition, we have explored the utility and mechanisms of natural products as potential TNBC therapeutics.