In which Neil Vasan, assistant professor of medicine and medical oncologist at the Columbia University Irving Medical Center, and Vaibhav discuss the biochemistry and structural biology of kinases, as well as their salience in cancer development and progression. Neil tells the story behind his critical discovery of hyper-activating double mutations cooccurring in cis on PI3K alleles, discusses his group's use of deep mutational scanning in elucidating mechanisms of drug resistance and disease pathogenesis, and describes his efforts to illuminate the dark phosphoproteome. As well, he discusses how proteomics complements genomic approaches to understanding cancer and provides advice for aspiring physician-scientists.