The laboratory undertakes research on the hematopoietic stem cells and progenitor populations, in normal mice and humans, and in neoplastic and genetic diseases. The laboratory has a long history of the using in vitro clonogenic assays for characterization of factors (e.g. G-CSF) involved in differentiation of hematopoietic progenitor cells into mature cells (Fig1). Subsequent studies, utilizing in vitro stem cell assays (Fig 2), have been directed at factors influencing stem cell proliferation, particularly cytokines favoring self-renewal rather than differentiation (ligands for c-Kit and flk2/flt3, Interleukins-1, -6, -11, thrombopoietin). Currently, retroviral, lentiviral and adenoviral gene delivery systems are being used to modify human stem cells self-renewal, differentiation and migration by introduction of genes for telomerase, Notch, CXCR4 and the HOX family. The process of leukemogenesis is being studied by transduction of normal human stem cells with leukemogenic genes such as bcr-abl, AML-ETO, Nup98/HOXA9 and mutated forms of Flt3 and Ras.
Malcolm A. S. Moore, DPhil