BSc Australian National University (1975)
MAppSci NSW Institute of Technology (1984)
PhD University of New South Wales (1988)
In 2015, I was appointed the Director of the UNSW Centre for Childhood Cancer Research. I am also the Deputy Director of Children’s Cancer Institute, the Co-Head of the Institute’s Molecular Targets and Cancer Therapeutics Theme and Head of the Molecular Oncology group. From 2010-19, I was Director of the ACRF Drug Discovery Centre, where we pioneered the development of cell-based high-throughput screening methodology of small-molecule libraries for child cancer and developed highly potent inhibitors of drug resistance proteins (MRPs) which led to the licensing of MRP4 inhibitors to the global biotech company, Abcam Plc.
My research interests focus on utilising new molecular genetic technologies to improve the diagnosis, risk classification and treatment of childhood cancer. My team was the first to develop and implement a unique PCR-based technology for the detection of minimal residual disease (MRD) in patients with acute lymphoblastic leukaemia (ALL), providing highly sensitive early detection of impending relapse. This doubled survival rates of children with high-risk ALL from 35% to over 70% and led to MRD testing becoming “standard of care” for all Australian children with ALL.
As an international expert in paediatric cancer research, particularly with regards to the molecular analysis of genes and their relationship with clinical variables, I have undertaken extensive research into the characterisation of genes involved in mediating resistance to chemotherapeutic drugs in paediatric leukaemia and neuroblastoma. My research is increasingly focused on understanding the regulation of the MYCN oncogene and its downstream targets, with the goal of developing molecular targeted therapies. My team and I have also pioneered several novel therapeutic strategies for the most aggressive child cancers, with many of these now translated into early phase clinical trials.
2022-2025 2021/TPG2112 Cancer Institute NSW Translational Program Grant
'Improving outcomes for children and young adults with sarcoma'
2021-2024 NHMRC Childhood Cancer Research (MRFF)
'Improving outcomes for children with high risk cancer'
2020-2023 Cancer Australia PdCCRS APP1188234/The Kids Cancer Project
'Enhanced polyamine depletion as a novel therapy for aggressive childhood cancers'
2020-2023 Australian Cancer Research Foundation
'The ACRF Child Cancer Liquid Biopsy Program'
2019-2021 Cancer Australia
'Targeting the NAD pathway as a new therapeutic strategy for high-risk leukaemia in children')
2019 Tour de Cure Foundation
A personalised medicine approach to the treatment of acute myeloid leukaemia in children'
2018-2020 NHMRC Development Grant
'Multidrug Resistance Protein 1 inhibitors to sensitise cancers to chemotherapy'
2018-2022 NHMRC Program Grant
'More effective therapeutic targeting of high-risk childhood cancer: Neuroblastoma as a model'
2011 Invited speaker, Minimal Residual Disease and Targeted Therapy in Children with ALL and neuroblastoma The Institute of Cancer Research / The Royal Marsden Hospital, Sutton, UK
2011 Invited Speaker, 70th Annual Meeting of the Japanese Cancer Conference, Nagoya, Japan “Targeting multidrug transporters in neuroblastoma”
2012 Invited Speaker, 3rd FEBS Special Meeting on ABC Proteins, Innsbruck, Austria 2012, “Targeting ABC transporters in childhood cancer”
2012 Cancer Institute NSW Premier’s Award for Translational Cancer Research
2012 NHMRC Program Grant was recognised in the “10 of the Best” Research Projects 2012
2014 Invited Speaker, 2014 International Academy of Pathology Meeting, Bangkok, Thailand
2014-2016 Elected Incoming President, Advances in Neuroblastoma Research Association
2015 Appointed a Member (AM) of the Order of Australia, for significant service to medical research as a molecular biologist and through pioneering development of treatments for cancer in children
2015 Shortlisted as a Finalist for The Australian Innovation Challenge Award, pioneering work in improving the survival rates of children with acute lymphoblastic leukaemia
2016-2018 President, Advances in Neuroblastoma Research Association
2019 Inaugural Sally Crossing Award for an Outstanding Outcome in Cancer Research, for his development of a new treatment approach for acute lymphoblastic leukeamia – doubling survival rates to over 70% today ($50,000)
2019-2020 Member, National Steering Committee, National Drug Discovery Centre, Walter and Eliza Hall Institute, Melbourne, VIC
I led the team that developed PCR-based technology to detect the presence of residual leukaemia in bone marrow of children after initial treatment for acute lymphoblastic leukaemia (ALL). These studies established my group as one of the leading international teams addressing this issue, showing that molecular detection of minimal residual disease (MRD) in paediatric ALL is a new approach to improving survival. My team was the first to report that relapse in children with ALL involves selection of a pre-existing drug-resistant subclone. This led to the first paediatric clinical trial employing molecular genetic testing to guide treatment in high-risk patients (ANZCHOG Study 8), which enrolled more than 650 children nationally over 10 years and saw the survival rates of children with high-risk ALL increase from 35% to about 70%. This molecular diagnostic testing platform, which my team developed and implemented, is now part of standard of care for children with ALL throughout Australia and now provides residual disease testing on more than 100 Australian children and adolescents annually. Based on the results of this testing, high-risk individuals are now stratified to receive alternate therapies. Research in the past five years by my group has continued to provide insights into relapsed and aggressive ALL, and has further improved detection methodology.
My seminal research on the role of the ABCC1/MRP1 multidrug transporter in neuroblastoma led to the first evidence of the clinical significance of this transporter in any human cancer and subsequently provided the first evidence for the clinical significance of the related transporter, ABCC4 and its ability to confer resistance to irinotecan/CPT-11, a drug now used to treat this disease. This research has led to an important shift in understanding the role of ABC multidrug transporter genes in cancer from one simply associated with drug resistance to one that extends to fundamental roles in tumour biology and maintenance of the inflammatory microenvironment. My team further extended this research on ABC transporter genes to ovarian cancer, leading to insights into the pathogenesis of the disease process and the definition of new clinical approaches.
MYCN amplification is the single most important biologic marker in childhood neuroblastoma. In collaboration with Professor Michelle Haber, my research has highlighted the significance of this oncogene in this disease and provided the first report of MYCN-mediated regulation of ABCC1. Building on this research, we provided the first comprehensive demonstration of a major role for Myc transcription factors in the direct and coordinate regulation (both positive and negative) of a large subset of the ATP binding cassette (ABC) transporter gene family, to which the ABCC genes belong. My team provided strong evidence that ABC transporters play a key role in generating a malignant and drug-resistance phenotype in neuroblastoma, with clinical implications for its treatment. Furthermore, we have also demonstrated that MYCN can contribute to multidrug resistance in cancer through the upregulation of a suite of drug-resistance genes covering a range of chemotherapeutic drugs.
My team also pioneered polyamine inhibition therapy, demonstrating that combining inhibition of polyamine synthesis and transport together with conventional chemotherapy, is highly promising as a therapy for neuroblastoma and potentially other MYC-driven cancers. This has eventuated in one completed international clinical trial in 15 children’s hospitals, one current trial open in 120 hospitals internationally, and two more being planned for neuroblastoma and for brain tumours.