Professor Don Metcalf
Details
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Division: Cancer & Haematology
Research Overview
Use is made of multiple in vitro clonal culture systems developed in this Unit to analyse the various cells involved in blood cell formation and the molecular control of these cells in health and disease, particularly leukaemia. There are two major current research activities:
- to establish whether blast colony-forming cells are the actual stem cells maintaining daily basal haematopoeisis. If so, the clonal cultures can be used to analyse the key molecular mechanisms controlling self-generation and commitment to various haemopoietic lineages
- to analyse the mechanisms by which overexpression of the homeobox gene Mixl1 or the abnormal fusion genes MLL-AF9 and MLL-ENU leads to myeloid leukaemia development.
Research Interests
- In vitro analysis of the control and behaviour of normal and preleukaemic haemopoietic precursor cells
- Analysis of the mechanisms underlying myeloid leukaemia development
Selected Publications
- Metcalf D, Glaser S, Mifsud S, Di Rago L, Robb, L. The preleukemic state of mice reconstituted with Mixl1-transduced marrow cells. Proc Natl Acad Sci USA 104:20013-2018, 2007.
- Emslie D, D'Costa K, Hasbold J, METCALF D, Takatsu K, Hodgkin PO, Corcoran LM. Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells. J Exp Med 205:409-421, 2008.
- Loughran SJ, Kruse, EA, Hacking DF, de Graaf CA, Hyland CD, Willson TA, Henly KJ, Ellis S, Voss AK, METCALF D, Hilton DJ, Alexander WS, Kile BJ. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol 9:810-819, 2008.
- Kauppi M, Murphy JM, de Graaf CA, Hyland CD, Greig KT, METCALF D, Hilton AA, Nicola NA, Kile BT, Hilton DJ, Alexander WS. Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl-/- mice. Blood 112:3148-3153, 2008.
- Metcalf D, Greig, KT, de Graaf, CA, Loughran, SJ, Alexander, WS, Kauppi, M, Hyland, CD, Di Rago L, Mifsud S. Two distinct types of murine blast colony-forming cell are multipotential hematopoietic precursors. Proc Natl Acad Sci USA 105:18501-18506, 2008.
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Current Laboratory Members
Faculty Member: Don Metcalf, AC BSc(Med) MD Syd FRACP HonDSc Syd HonMD Oslo HonFRCPath London FRCPA FAA FRS
Research Assistant: Ladina Di Rago
Research Assistant:Sandra Mifsud, BAppSc RMIT