The Walter and Eliza Hall Institute of Medical Research

Dr Matthew McCormack

Details

Email: .(JavaScript must be enabled to view this email address)
Division: Cancer & Haematology

Research Overview

Stem cells replenish our tissues throughout life. To achieve this, they have the property of self-renewal, in which stem cells divide without maturing. However, cancer-causing mutations can give self-renewal abilities to cells that have normally lost this property. These cells then persist long-term as “precancerous stem cells” whilst acquiring additional mutations that lead to overt cancer. Precancerous stem cells are intrinsically resistant to conventional cancer therapy, implying that they may be a source of disease relapse.

Our laboratory studies precancerous stem cells that cause T cell leukaemia. We aim to discover the self-renewal pathways that are induced by cancer-causing genes that give self-renewal properties to developing T cells in the thymus. We also study the role of these genes in normal blood stem cell function.

In addition, we are investigating therapeutic strategies to target precancerous stem cells in T cell leukaemia.

Research Interests

• Self-renewal pathways induced by transcription factor oncogenes in T cell leukaemia
• Therapeutic targeting of preleukaemic stem cells
• Transcriptional regulation of haemopoietic stem cell function

Selected Publications

1. Curtis DJ, McCormack MP. The molecular basis of Lmo2-induced T-cell acute lymphoblastic leukemia. Clin Cancer Res. 2010 Dec 1; 16(23):5618-23. PMID: 20861166
2. McCormack MP, Young LF, Vasudevan S, de Graaf CA, Codrington R, Rabbitts TH, Jane SM, Curtis DJ. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science. 2010 Feb 12:327(5967):879-83. PMID: 20093438
3. McCormack MP, Hall MA, Schoenwaelder SM, Zhao Q, Ellis S, Prentice JA, Clarke AJ, Slater NJ, Salmon JM, Jackson SP, Jane SM, Curtis DJ. A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis. Blood. 2006 Oct 1:108(7)2248-56. PMID: 16763211
4. McCormack MP, Rabbitts TH. Activation of the T-cell oncogene LMO2 after gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2004 Feb 26;350(9)913-22. PMID: 14985489
5. Forster A, Pannell R, Drynan LF, McCormack M, Collins EC, Daser A, Rabbitts TH. Engineering de novo reciprocal chromosomal translocations associated with Mll to replicate primary events of human cancer. Cancer Cell. 2003 May;3(5):449-58. PMID: 12781363
6. McCormack MP, Forster A, Drynan L, Pannell R, Rabbitts TH. The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development. Mol Cell Biol. 2003 Dec;23(24):9003-13. PMID: 14645513
7. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, de Saint Basile G, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, Le Deist F, Fischer A, Cavazzana-Calvo M. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003 Oct 7;302(5644):415-9. PMID: 14564000
8. McCormack MP, Gonda TJ. Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the GM-CSF receptor beta subunit. Blood. 2000 Jan 1;95(1):120-7. PMID: 1060794
9. McCormack MP, Gonda TJ. Myeloproliferative disorder and leukaemia in mice induced by different classes of constitutive mutants of the human IL-3/IL-5/GM-CSF receptor common beta subunit. Oncogene. 1999 Dec 2;18(51)7190-9. PMID: 10602472
10. McCormack MP, Gonda TJ. Expression of activated mutants of the human interleukin-3/interleukin-5/granulocyte-macrophage colony-stimulating factor receptor common beta subunit in primary hematopoietic cells induces factor-independent proliferation and differentiation. Blood. 1997 Aug 15;90(4):1471-81. PMID: 9269764

Click here to view more PubMed publications

Current Laboratory Members

Faculty Member: Matthew McCormack, BSc(Hons), PhD Adelaide

Senior Postdoctoral Fellow: Benjamin Shields, PhD Melb

Research Assistant: Jacob Jackson BSc(Hons), Melb GradDipArts Melb

Postgraduate Student Raed Alserihi, BSc King Abdulaziz MSc RMIT

Honours student: Hesham Abdulla, BAppSci RMIT