My career as a physician-scientist has combined diagnostic hematopathology with research in the molecular biology of acute leukemia. Specifically my research has focused on the mechanisms of Hox gene regulation by the mixed lineage leukemia protein, MLL, transcriptional deregulation by MLL fusion proteins, and the role of Hox genes in hematopoiesis and leukemia. Perhaps our single most significant discovery was that MLL is a histone methyltransferase. Working with Dr. Matthew Meyerson, we discovered that MLL interacts with the tumor suppressor menin. We also determined that MLL interacts with the polymerase-associated factor PAF and that MLL fusion proteins recruit a complex including the DOT1 methyltransferase. The MLL-menin, MLL-PAF interactions and DOT1 are all required for MLL mediated leukemogenesis and represent attractive therapeutic targets. Our current work is focused on developing small molecule inhibitors of these mechanisms in collaboration with a highly successful interdisciplinary team that I recruited during my years as Chair of Pathology at the University of Michigan.