Novel Kinases Driving Cancer
We will determine whether protein kinases newly implicated in cancer by the presence of putative driver mutations, identified in cancer genome sequencing studies, do in fact play a role in tumorigenesis. We will focus initially on four protein kinases that include DAPK3 among other cancer-associated kinases. These kinases scored high in the ranking system I devised as being the most likely to play a role in cancer. We will carry out in vitro and in vivo analysis of kinase activity and determine the phenotypic consequences of expressing mutant or WT kinases in normal or cancer cells, assaying for effects on proliferation, cell cycle progression, apoptosis/autophagy, morphological transformation, anchorage independent growth, and tumorigenesis. We will identify cancer relevant substrates for mutant and WT kinases thereby defining signaling pathway(s) in which these mutant kinases act to promote tumorigenesis. Once causal cancer-associated kinases are identified, we hope to be able to define convergent pathways aberrantly regulated by these kinases and thereby pinpoint pathways that can be therapeutically targeted for the treatment of cancer.