Curtis/Ting Group - Stem Cell Biology
Division of Blood Cancers
Key terms: Blood stem cells, stem cell biology
To understand the regulation of stem cells in haematopoietic and leukaemic stem cells through genetic and epigenetic studies.
Research Focus and Tools
- The basic HLH transcription factor complex
- Self-renewal and asymmetrical cell division
- Quiescence and therapeutic resistance
- Transgenesis and viral mouse models of leukaemia, myelodysplasis and myeloproliferative neoplasms
- Live cell imaging. View videomicroscopy of histone H2B-GFP HSC transduced with cherry-AP2A2 (in orange) on OP9 cells, showing asymmetrical segregation of AP2A2 in mitosis. Scale bar 30 microm. (2Mb download) 8.3MB 4:19 min.
2020 group L-R Back Row: Professor David Curtis, Mr Feng Yan, Mr Andrej Terzic. Front Row: Ms Jacqueline Boyle, Ms Shokoufeh Abdollahi, Dr Cedric Tremblay, Ms Jesslyn Saw, Dr Christina Makhlouf, Absent: Dr Emma Toulmin, Mr James The, Ms Anna Leichter
Tissue-specific stem cells replenish the mature, functional cells of that tissue throughout the life of the organism. Self-renewal and cell quiescence are important properties of normal stem cells that must be tightly regulated to maintain homeostasis. The goal of the Stem Cell Research Group is to understand the regulation of self-renewal and cell quiescence in normal HSCs and how these processes are perturbed in acute leukaemia. This research has broad therapeutic implications for ex vivo expansion of stem cells for bone marrow transplantation or regenerative medicine and identifying new ways of killing quiescent leukemic stem cells.
Projects and Opportunities
For current project opportunity descriptions please visit our honours page
Tremblay C.S, Chiu S.K, Saw J, McCalmont H, Litalien V, Boyle J, Sonderegger S.E, Chau N, Evans K, Cerruti L, Salmon J.M, McCluskey A, Lock R.B, Robinson P.J, Jane S.J, Curtis D.J. Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells. Nature Communications, Dec 2020, 11(1):6211 doi: 10.1038/s41467-020-20091-6
Guirguis, AA., Slape, CI., Failla, LM., Saw, J., Tremblay, CS., Powell, DR., Rossello, F., Wei, A., Strasser, A., Curtis, DJ., 2016, PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia, Cell Death and Differentiation, vol 23, pp. 1049–1059.
Tremblay, CS., Brown, FC., Collett, M., Saw, J., Chiu, SK., Sonderegger, SE., Lucas, SE., Alserihi, R., Chau, N., Toribio, ML., McCormack, MP., Chircop, M., Robinson, PJ., Jane, SM., Curtis, DJ., 2016, Loss-of-function mutations of Dynamin 2 promote T-ALL by enhancing IL-7 signalling, Leukemia advance online publication 13 May 2016; doi: 10.1038/leu.2016.100
McQuilten, Z., Sundararajan, V., Andrianopoulos, N., Curtis, D.J., Wood, E.M., Campbell, L.J., Wall, M., 2015, Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes, Cancer [P], vol 121, issue 17, John Wiley & Son, Inc., Hoboken NJ United States, pp. 2892-2899.
Pham, T., Patil, S., Fleming, S.A., Avery, S., Walker, P.A., Wei, A., Curtis, D.J., Stuart, G., Klarica, D., O'Brien, M., Morris, K., Das, T.P., Bollard, G.M., Muirhead, J., Coutsouvelis, J., Spencer, A., 2015, Comparison of biosimilar filgrastim with originator filgrastim for peripheral blood stem cell mobilization and engraftment in patients with multiple myeloma undergoing autologous stem cell transplantation, Transfusion [P], vol 55, issue 11, Wiley-Blackwell Publishing, Inc., USA, pp. 2709-2713.
Taylor, M., Curtis, D.J., Teter, K., 2015, A conformational shift in the dissociated cholera toxin A1 subunit prevents reassembly of the cholera holotoxin, Toxins [E], vol 7, issue 7, M D P I AG, Basel Switzerland, pp. 2674-2684.
Campbell, P., Walker, P.A., Avery, S., Curtis, D.J., Schwarer, A., Wei, A., Kalff, A., Muirhead, J.L., Spencer, A., 2014, Safe and effective use of outpatient non-myeloablative allogeneic stem cell transplantation for myeloma, Blood Cancer Journal [E], vol 4, issue 5, Macmillan Publishers Limited, London, N1 9XW United Kingdom, p. e213.
McQuilten, Z., Wood, E.M., Polizzotto, M.N., Campbell, L., Wall, M., Curtis, D.J., Farrugia, H., McNeil, J.J., Sundararajan, V., 2014, Underestimation of myelodysplastic syndrome incidence by cancer registries: results from a population-based data linkage study, Cancer [P], vol 120, issue 11, John Wiley & Sons, United States, pp. 1686-1694.
Tremblay, C., Curtis, D.J., 2014, The clonal evolution of leukemic stem cells in T-cell acute lymphoblastic leukemia, Current Opinion In Hematology [P], vol 21, issue 4, Lippincott Williams & Wilkins, United States, pp. 320-325.
NHMRC project grants:
- APP1052313 (2013-15): The bHLH transcription factor LYL1 in normal and leukemic hematopoiesis PIs: Curtis, Pimanda and McCormack.
- APP1047554 (2013-15): Endocytosis and asymmetric cell division in leukemia. PIs: Ting and Curtis.
- APP1086662 (2015-2018): Eradicating leukaemic stem cells by targeting the arginine methyltransferase PRMT5. PIs: Curtis, Jane, Haigh, Wei and Powell.