The focus of my research involves the identification of genetic lesions underlying cancer pathogenesis with the ultimate goal of discovering specific, gene-targeted therapies that can be individually tailored to cancer patients on the basis of these causative oncogenic lesions. We aim to understand the mechanisms underlying drug combination efficacy and have identified combinations of inhibitors spanning different drug classes that have the potential to be effective therapies for AML. To accomplish this goal our group has developed powerful functional screening strategies utilizing genome-wide CRISPR/Cas9 sgRNA libraries to identify gene knockouts which confer drug resistance. Once we have identified genes of interest, we validate and uncover mechanisms by which mutations in a given pathway lead to drug resistance. We have also begun single cell analysis on primary samples from AML patients using CITE-seq to further characterize specific cell population gene expression and surface protein expression patterns after exposure to treatments of interest.