Mutations in cancer cells lead to malfunctioning control of gene expression. Our laboratory is dedicated to discovering the gene expression control factors that are essential for leukemia and lymphoma cell survival. Discovery of these factors prompts further efforts in our group to design chemical strategies for the synthesis and deployment of prototype drugs targeting the aberrant mechanisms of gene control. Biologically, gene control factors represent compelling therapeutic targets for these cancers, as they are master regulators of cell identity. Yet despite this clear rationale, most are perceived as intractable drug targets owing to their large size, disordered shapes, and involvement in complex cellular circuits. Recent advances in gene editing technologies and discovery chemistry have advanced our capability to rapidly identify targetable aspects of gene control and methods to disrupt their function. We use these genetic and chemical tools to probe cancer cell circuitry and inform therapeutic hypotheses.