Mike Hemann’s training and research has focused development of models of cancer evolution and therapeutic response. As a graduate student, he investigated mouse models of telomere dysfunction in Carol Greider’s laboratory. As a post-doctoral fellow in Scott Lowe’s laboratory at Cold Spring Harbor Laboratory, he sought to develop tractable mouse models that could be used with the same ease as classic genetic model organisms to interrogate the genetics of cancer progression and treatment. The result of these efforts has been the development of diverse approaches that be directly applied to investigating mechanisms of tumor drug resistance. His group has made extensive use of mice as preclinical systems to examine therapeutic efficacy and have developed hematopoietic and solid tumor models that can effectively interrogate aspects of acquired and intrinsic drug resistance. A particular focus of this work is to develop strategies to sensitize tumors to front-line chemotherapy. The Hemann lab has pioneered the development of novel screening strategies to characterize the genetic determinants of drug action in relevant physiological settings. They have also been able to extend this work into the clinic in the context of treatment refractory malignancies. Their consistent objective is the development of combination drug regimens that can subvert the evolution of drug resistance.