The goal of the research in our lab is to investigate the genetics and signaling pathways that drive acute myeloid leukemia (AML) to provide a foundation for the development of novel targeted treatment approaches. Our research is focused on identifying the critical mediators of RAS signaling that drive AML growth and survival using molecular genetic approaches in the most clinically relevant genetically engineered mouse models, human AML cell lines, and primary AML patient samples in vitro and in patient-derived AML xenografts. We are evaluating the role of clinically-relevant biochemical signaling pathway inhibitors alone and in combination with novel chemotherapeutic and immunotherapy approaches to maximize the translational potential of our studies. We are utilizing cutting-edge multi-parameter flow cytometry and next generation sequencing to characterize AML treatment response and identify potential mechanisms of treatment resistance. In total, these translational studies will provide novel insights for the development of rationally designed targeted therapies for human AML.