The Walter and Eliza Hall Institute of Medical Research

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; (a) to establish whether blast colony-forming cells can be used as surrogates of the important haemopoietic stem cells or are indeed stem cells. If so, the clonal cultures can be used to analyse the key molecular mechanisms controlling self-generation and commitment to various haemopoietic lineages, (b) to analyse the mechanisms by which overexpression of the homeobox gene Mixl1 leads to myeloid leukaemia development.

Research Projects

In vitro analysis of the control and behaviour of haemopoietic precursor cells.

Analysis of the mechanisms underlying myeloid leukaemia development.

Major Publications

1. 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.
2. 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.
3. 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.
4. 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.
5. 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) Syd FAA FRS FRACP HonDSc Syd HonMD Oslo HonFRCPath London MD Syd FRCPA

Research Assistant: Ladina Di Rago

Research Assistant:Sandra Mifsud, BAppSc RMIT