My current research focus is on the regulation and biological function of signal transduction pathways in the context of human cancer - especially as they relate to therapeutic opportunities. I am particularly interested in the role of protein kinase-mediated signaling pathways. There are more than 500 kinases encoded by the human genome - many of which have been implicated in cancer - and we are exploring mechanisms of molecularly-targeted cancer therapeutics that influence kinase-mediated signaling pathways that are dysregulated during human tumorigenesis.

We are also trying to develop a better understanding of the 'oncogene addiction' phenomenon. Oncogene addiction refers to the acquired dependency of cancer cells on a single cellular pathway or protein for survival or sustained proliferation, despite the fact that such cells have undoubtedly accumulated numerous genetic alterations. We have conducted studies that reveal a potential mechanism to explain the striking sensitivity of certain tumors that are addicted to mutationally activated kinases. 

Finally, we are interested in understanding the mechanisms by which cancer cells become resistant to targeted drugs that disrupt signaling pathways, which remains an important limitation to their clinical utility. We have developed several in vitro models of drug resistance and we are examining the relationship between a newly identified sub-population of cancer cells that we describe as 'reversibly drug tolerant' and the more stable forms of genetically-mediated drug resistance. These studies have sparked an additional interest in the role of epigenetics and tumor heterogeneity in the response to molecularly-targeted cancer therapies.