Jim’s interest is in the mechanism of transformation used by different leukemia fusion oncoproteins found in human AML, in particular the Core Binding Factor fusions and the MLL fusions. The genes targeted by these chromosomal translocations play critical roles in normal hematopoiesis and also in leukemogenesis. Together, these genetic aberrations account for 25-30% of all human AML cases. The Mulloy Lab is developing relevant in vivo models of human leukemia using leukemia fusion gene expression in primary human blood stem cells. His lab has developed a “next generation” mouse that is superior for expanding human leukemia samples in vivo. They are using this model in chemotherapy studies to establish a system for testing experimental compounds for efficacy against human leukemia. Other work in the lab is focused on the molecular signals downstream of the leukemia fusion oncoproteins. These studies are aimed at gaining a better understanding of the mechanism of action of these leukemia oncogenes to assist in identifying novel molecules for therapeutic targeting.
Benjamin graduated from the University of Utah School of Medicine and came to Cincinnati Children's for residency training in pediatrics and fellowship training in Hematology/Oncology. He studies the role of the Rac family of small Rho GTPases in myeloid leukemogenesis. His work explores targeting Cdc42 to displace the leukemic stem cell from its protective microenvironment.
Mark is characterizing a new strain of NOD/SCID mouse, the NSGS mouse, as a tool for xenograft studies of human AML and normal hematopoiesis. The lab is currently using this xenograft AML model to study chemotherapeutic potential of novel small molecule inhibitors.