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A/Prof Carl Walkley

Research Unit

Stem cell regulation

Information

Co-Head, Stem Cell Regulation Unit
Victorian Cancer Agency Mid-Career Research Fellow

Professional Experience

1997       BPharm, University of South Australia
1999       BPharm (Hons), University of South Australia
2003       PhD, Peter MacCallum Cancer Centre, University of Melbourne
2004-07  Post-doctoral Fellow, Dana-Farber Cancer Institute and Children's Hospital Boston, Boston, USA
2008       Co-Head, Stem Cell Regulation Unit, St Vincent's Institute
2008-15  Honorary Fellow, Department of Medicine, University of Melbourne
2015       Associate Professor (Honorary Principal Fellow), Department of Medicine, St. Vincent’s Hospital, University of Melbourne

Achievements

2000-03    Australian Postgraduate Award
2006-09    Special Fellow Award, Leukemia & Lymphoma Society USA
2009-12    NHMRC Career Development Award Level 1
2010-14    Leukaemia Foundation Philip Desbrow Senior Research Fellow
2016-19    NHMRC Career Development Award Level 2 (awarded but declined)
2016-19    Victorian Cancer Agency Mid-Career Research Fellow

Research Interests

My research focuses on two major areas: understanding the role of RNA editing, in particular by ADAR1, in homeostasis and disease and in generating and applying models of human cancer (myelodysplastic syndrome and osteosarcoma).

We use haemopoiesis as the primary model system to understand the role of RNA editing by ADAR1 in normal homeostasis and disease.

We are also interested in generating faithful models of human cancer. We have established several models of osteosarcoma (the most common type of bone cancer) and have also been developing models of a type of blood cancer called myeloproliferative/myelodysplastic syndrome. We use information from human cancers and familial cancer predispositions to enable us to develop these models to be as faithful as possible to the human cancer we are modelling.

Selected Publications

  1. WALKLEY, C.R., Fero, M.L., Chien, W-M., Purton, L.E.* & McArthur, G.A.*. (2005) Negative Cell Cycle Regulators Co-Operatively Control Self-Renewal and Differentiation of Haemopoietic Stem Cells. Nat Cell Biol 7,172-8.
  2. WALKLEY, C.R., Shea, J.M., Sims, N.A., Purton, L.E. & Orkin, S.H. (2007) Rb Regulates Interactions Between Hematopoietic Stem Cells and their Bone Marrow Microenvironment. Cell 129, 1081-1095.
  3. WALKLEY, C.R.*, Haines Olsen, G.*, Dworkin, S., Fabb, S.A., Swann, J., McArthur, G.A., Westmoreland, S.V., Chambon, P., Scadden, D.T. & Purton, L.E. (2007) A Microenvironment-Induced Myeloproliferative Syndrome Caused by Retinoic Acid Receptor γ Deficiency. Cell 129, 1097-1110.
  4. Sankaran, V.G., Orkin, S.H. & WALKLEY, C.R. (2008) Rb Intrinsically Promotes Erythropoiesis by Coupling Cell Cycle Exit with Mitochondrial Biogenesis. Genes & Dev 22, 463-475.
  5. Walkley, C.R., Qudsi, R., Sankaran, V.G., Perry, J.A., Gostissa, M., Roth, S.I., Rodda, S.J., Snay, E., Dunning, P., Fahey, F.H., Alt, F.W., McMahon, A.P. & Orkin, S.H. (2008) Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes & Dev 22, 1662-1676.
  6. Smeets MF, DeLuca E, Wall M, Quach JM, Chalk AM, Deans AJ, Heierhorst J, Purton LE, Izon DJ, Walkley CR. The Rothmund-Thomson Syndrome helicase Recql4 is essential for hematopoiesis. J Clin Invest (2014) 124:3551-3565.
  7. Ng AJ, Walia MK, Smeets MF, Mutsaers AJ, Sims NA, Purton LE, Walsh NC, Martin TJ, Walkley CR. The DNA Helicase Recql4 Is Required for Normal Osteoblast Expansion and Osteosarcoma Formation. PLoS Genet. 2015 Apr 10;11(4):e1005160.
  8. Gupte A, Baker EK, Wan SS, Stewart E, Loh A, Shelat AA, Gould CM, Chalk AM, Taylor S, Lackovic K, Karlström Å, Mutsaers AJ, Desai J, Madhamshettiwar PB, Zannettino ACW, Burns C, Huang DCS, Dyer MA, Simpson KJ, Walkley CR. Systematic screening identifies dual PI3K and mTOR inhibition as a conserved therapeutic vulnerability in osteosarcoma. Clin Cancer Res 2015 July 15,21:3216-3229.
  9. Liddicoat BJ, Piskol R, Chalk AM, Ramaswami G, Higuchi M, Hartner JC, Li JB, Seeburg PH, Walkley CR. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as non-self. Science 2015 Sep 4;349(6252):1115-20.
  10. Walia M, Ho PM, Taylor S, Ng AJM, Gupte A, Chalk AM, Zannettino ACW, Martin TJ, Walkley CR. Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance. eLife 2016