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
Research FocusCell biologist Malcolm Moore focuses on the characterization of normal and cancer stem cells and the development of selective therapies.
EducationD. Phil, University of Oxford
- The Molecular Basis of Human Leukemia: Evaluation by the Application of Forward and Reverse Genetics
- Telomerase and Telomere Dynamic in Normal and Malignant Stem Cells
- Human and Murine Embryonic Stem Cell Program
- Adult and Umbilical Cord Blood Hematopoietic Stem Cell Expansion
- Endothelial Cell Biology
- Lee J, Shieh JH, Zhang J, Liu L, Zhang Y, Morrone G, Moore MAS, and Zhou P. Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4. BLOOD. Blood. 2013 May 16;121(20):4082-9. doi: 10.1182/blood-2012-09-455204. Epub 2013 Mar 21. PMID: 23520338
- Hartwell KA, Peter G Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Järås M, Puram R, Dancik V, Al-Shahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh J-H, Steensms DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MAS*, Scadden DT*, Schreiber SL*, Ebert BL*, Golub TR*. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol. 2013 Dec;9(12):840-8. *co-senior authors PMID:24161946