My research focus is on the investigation of cellular and molecular mechanisms underlying human hematopoietic stem cell transformation in myeloid leukemias, including chronic myelogenous leukemia (CML) and myelodysplasia (MDS) and acute myelogenous leukemia (AML), and translating this knowledge to…
more the development of innovative mechanism-based therapeutic strategies to effectively and selectively target malignant stem cells in these disorders. We are investigating mechanisms underlying resistance of malignant stem cells in CML patients to targeted therapies, and are developing improved mechanism-based therapeutic approaches to target residual stem cells. We are also using a model of human stem cell transformation in CML based on ectopic expression of the BCR/ABL: gene in normal CD34+ cells to determine mechanisms critical to stem cell transformation in CML. In another major project in our laboratory, we are investigating the serial evolution of cellular and molecular abnormalities in hematopoietic stem cells during myeloid leukemogenesis through intensive study of a cohort of lymphoma patients at high risk for development of therapy-related MDS/AML. The overall aims of these studies include improved understanding of early events in leukemogenesis, identification of patients at risk or in early stages of development of leukemia and development of novel preventive or therapeutic strategies.
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