Our research focuses on modeling leukemia using human hematopoietic stem and progenitor cells (HSPC). This allows us to establish relevant model systems to dissect the process of human myeloid and lymphoid leukemogenesis and to investigate the prevailing theory that acute myeloid leukemia is a stem cell disease.
We are focusing on three of the most common types of human leukemia: those associated with translocations between chromosomes 8 and 21, aberrations of chromosome 16, and translocations involving chromosome 11q23 that affect the MLL gene. Together, the subtypes of leukemia associated with these genetic lesions account for about 30 percent of all human acute leukemia cases.
Our studies of human leukemogenesis aim to answer a number of research questions. We want to understand the effects of AML1-ETO expression on the self-renewal and differentiation properties of human HSPC. We seek to identify the domains of AML1-ETO and the binding partners that are critical for function of the protein. We hope to develop relevant in vivo models of human leukemia using transplantation of these cells into immunocompromised mouse models, and intend to use these mouse models for therapeutic testing of novel compounds. Finally, we are investigating the role played by the Rac, Cdc42 and Rho proteins, members of the Rho family of small GTPases, in the development and maintenance of leukemia.