A/Professor Paul Ekert
Associate Professor Paul Ekert is a qualified paediatrician and researcher who has worked as a specialist at The Royal Children's Hospital Neonatal Unit for 14 years. He has also worked at the Walter and Eliza Hall Institute of Medical Research, both as a postdoctoral scientist and as a laboratory head. Associate Professor Ekert's associations with the Murdoch Childrens Research Institute and the Royal Children's Hospital go back many years to his days as a paediatric trainee at the hospital, and his first position as a research laboratory head in the Children's Cancer Centre.
- Eric Burnard Travelling Fellowship, Royal Australasian College of Physicians, 1997
- Postdoctoral Fellowship, Murdoch Childrens Research Institute, Melbourne, Australia, 1999
- NHMRC Career Development Grant, 2002
- Discovery Award, Murdoch Childrens Research Institute, 2008
- Sylvia and Charles Viertel Senior Medical Fellowship, 2008
Associate Professor Ekert's research team aims to understand the molecular basis of cancer and to use this knowledge to develop better diagnostics and treatments for children with malignant cancer.
His research has focused on aspects of programmed cell death (or apoptosis), particularly on the intersections between cytokine signalling pathways and cell death pathways. A key discovery in the field of apoptosis research was that many cell types rapidly activated intrinsic cell death pathways. This process is regulated by the Bcl-2 family of proteins when they lose the signals from cytokines. This meant that cytokines, signalling through their receptors on the cell surface, directly regulated whether cells remained viable or would die. Importantly, the signalling pathways activated by these cytokines have important roles in contributing to the development of cancer, particularly when they are abnormally activated. The team studies acute myeloid leukaemia to examine cytokine signalling in cancer and how new drugs might target these pathways.
An important new focus of Associate Professor Ekert's research group is to use the genomics techniques to detect these changes and translate this knowledge to guide treatments. The team works with groups in Melbourne and around Australia to develop genomics as a core part of the diagnostic workup of children with cancer.
- Investigating the cellular and molecular biology of oncogenes and translocations.
- Molecular Cytogenetics of Neuroblastoma – SNP arrays and targeted exome sequencing.
- Developing targeted exome sequencing and other techniques for paediatric cancers
- Proteomic Biomarkers in Acute Myeloid Leukaemia (AML)
- Targeting IAPs in models of paediatric cancer
Jabbour AM, Daunt CP, Green BD, Vogel S, Gordon L, Lee RS, Silke N, Pearson RB, Vandenberg CJ, Kelly PN, Nutt SL, Strasser A, Borner C, Ekert PG (2010) Myeloid progenitor cells lacking p53 exhibit delayed upregulation of Puma and prolonged survival after cytokine deprivation. Blood 115:344-352
Hahn CN, Chong CE, Carmichael CL, Wilkins EJ, Brautigan PJ, Li XC, Stankovic M, Lin M, Carmagnac A , Lee YK, Butcher CM, Friend KL, Ekert PG, Kok CH, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Ng B, Escher R, Bardy PG, Suthers GK, D'Andrea RJ, Horwitz MS, Scott HS (2011) Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet 43: 1012-1027
Sandow JJ, Jabbour AM, Condina MR, Daunt CP, Stomski FC, Green BD, Riffkin CD, Hoffmann P, Guthridge MA, Silke J, Lopez AF, Ekert PG (2011) Cytokine receptor signaling activates an IKK dependent phosphorylation of PUMA to prevent cell death. Cell Death Differ 19:633-641.
Thomas D, Powell JA*, Green BD, Barry EF, Ma Y, Woodcock J, Fitter S, Zannettino ACW, Pitson SM, Hughes TP, Lopez AF, Shepherd PR, Wei AH, Ekert PG, Guthridge MA (2013) Protein Kinase Activity of Phosphoinositide3-kinase Regulates Cytokine-Dependent Cell Survival. PLOS Biology, 11(3);e1001515
Benjamin D Green, Anissa M Jabbour, Jarrod J Sandow, Christopher D Riffkin, Dimitra Masouras, Carmel P Daunt, Marika Salmanidis, Gabriela Brumatti, Brian A. Hemmings, Mark A Guthridge, Richard B Pearson and Paul G Ekert (2013) Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. Cell Death and Differentiation. 20:1341-1349.
Marika Salmanidis, Gabriela Brumatti, Nisha Narayan, Benjamin D Green, Jocelyn A van den Bergen, Jarrod J Sandow, Andrew G Bert, Natasha Silke, Rosemary Sladic, Hamsa Puthalakath, Leona Rohrbeck, Toru Okamoto, Philippe Bouillet, Marco J Herold, Gregory J Goodall, Anissa M Jabbour and Paul G Ekert (2013) Hoxb8 regulates expression of microRNAs to control cell death and differentiation. Cell Death and Differentiation. 20: 1370-1380
Gabriela Brumatti, Marika Salmanidis, Chung H Kok, Rebecca Bilardi, Natasha Silke, Jarrod J Sandow, Kylie Mason, Jolanda Visser, Anissa M Jabbour, Stefan P Glaser, Toru Okamoto, Philippe Bouillet, Richard J D'Andrea, and Paul G Ekert (2013) HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent Leukemia. Oncotarget 4: 1933-1947
Jarrod J Sandow, Loretta Dorstyn, Lorraine A O'Reilly, Maximilien Tailler, Sharad Kumar, Andreas Strasser, Paul G Ekert (2014) ER stress does not cause up-regulation and activation of caspase-2 to initiate apoptosis. Cell Death and Differentiation 21: 475-480.
Pratiti Bandopadhayay, Anissa M Jabbour, Christopher Riffkin, Marika Salmanidis, Lavinia Gordon, Dean Popovski, Lin Rigby, David M Ashley, David N Watkins, David M Thomas, Elizabeth Algar, Paul G Ekert (2013). The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts. BMC Cancer e-citation"> 2013, 13:585?
James A. Rickard, Joanne A. O'Donnell, Joseph M. Evans, Najoua Lalaoui, Ashleigh R. Poh, TeWhiti Rogers, James E. Vince, Kate E. Lawlor, Robert L. Ninnis, Holly Anderton, Cathrine Hall, Sukhdeep K. Spall, Toby J. Phesse, Helen E. Abud, Louise H. Cengia, Jason Corbin, Sandra Mifsud, Ladina Di Rago, Donald Metcalf, Andrew W. Roberts, Warren S. Alexander, James M. Murphy, Paul G. Ekert, Seth L. Masters, Ben A. Croker, Motti Gerlic, John Silke (2014) RIPK1 regulates MLKL-RIPK3 driven systemic inflammation and emergency hematopoiesis Cell 157(5): 1175-1188.
Sadras, T., Perugini, M., Kok, C. H., Iarossi, D. G., Heatley, S. L., Brumatti, G., Samuel, M. S., To, L. B., Lewis, I. D., Lopez, A. F., Ekert, P. G., Ramshaw, H. S., D'Andrea, R. J. (2014) Interleukin-3-mediated regulation of beta-catenin in myeloid transformation and acute myeloid leukemia Journal of Leukocyte Biology 96(1):83-91.
Lalaoui, N., Johnstone, R., Ekert, P. G. (2015) Autophagy and AML-food for thought. Cell Death Differ 10.1038/cdd.2015.136
Najoua Lalaoui, Kay Hänggi,Gabriela Brumatti, Diep Chau, Nhu-Y N. Nguyen, Lazaros Vasilikos, Lisanne Spilgies, Denise A. Heckmann, Chunyan Ma, Margherita Ghisi, Jessica M. Salmon, Geoff Matthews, Elisha de Valle, Donia Moujalled, Manoj B. Menon, Sukhdeep Kaur Spall, Stefan P. Glaser, Jennifer Richmond, Richard B. Lock, Stephen M. Condon, Raffi Gugasyan, Matthias Gaestel, Mark Guthridge, Ricky W Johnstone, Lenka Munoz, Andrew Wei, Paul G. Ekert, David L. Vaux, W. Wei-Lynn Wongand John Silke (2016) Targeting p38 or MK2 enhances the anti-leukemic activity of Smac-mimetics Cancer Cell 29;145-154
Gabriela Brumatti, Chunyan Ma, Najoua Lalaoui, Nhu-Y Nguyen, Mario Navarro, Maria Tanzer,Jennifer Richmond, Margherita Ghisi, Jessica M. Salmon,Natasha Silke, Giovanna Pomilio, Stefan P. Glaser, Elisha de Valle, Raffi Gugasyan, Mark A. Gurthridge, Stephen M. Condon, Ricky W. Johnstone, Richard Lock, Guy Salvesen, Andrew Wei,David L. Vaux, Paul G. Ekert and John Silke (2016) The caspase-8 inhibitor emricasan combines with the Smac-mimetic birinapant to induce necroptosis and treat Acute Myeloid Leukemia. Science Translational Medicine 8(339);339ra69.?
Nisha Narayan, Leah Morenos, Belinda Phipson, Simon N. Willis, Gabriela Brumatti, Stefanie Eggers, Najoua Lalaoui, Lauren M. Brown, Hansen J. Kosasih, Ray C. Bartolo, Li Zhou, Daniel Catchpoole, Richard Saffery, Alicia Oshlack, Gregory J. Goodall, Paul G. Ekert (2016) Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukemia. Leukemia.10.1038/leu.2016.279