The Cancer group studies the molecular basis of childhood cancer and how understanding this can be translated into improved diagnostics and treatments.
The laboratory has a long-standing interest in the way cytokines signal in blood cells and how such signals are altered in cancer. Led by A/Professor Ekert, the team are using signalling models to explore how mutations in genes involved in this signalling change the behaviour of cells. This also includes analysis into how cancer genes alter the expression of proteins on the surface of blood cells using advanced proteomic techniques.
The Cancer group also has an evolving interest in the genomic changes that occur in cancer cells. They are investigating new ways to identify these changes, including using new sequence techniques to identify balanced translocations.
Murdoch Children's Research Institute acknowledges the longstanding and significant support of the Children's Cancer Foundation in partnership with My Room and the Steven Walter Children’s Cancer Foundation in funding our cancer research. Since 2002 the Children's Cancer Foundation and its funding partners have invested $7 million to support a broad program of childhood cancer research. This support includes research project funding, clinical trial staffing, clinical research training fellowships, and establishment and support of biobanking. In 2004 the Children's Cancer Foundation fully funded the construction and fit out of the Children’s Cancer Centre Laboratory at Murdoch Children's and also purchased vital laboratory equipment which underpins the work of our cancer research teams.
Investigating the cellular and molecular biology of oncogenes and translocations.
The aims of this project are to isolate rare cancer translocations form prospectively banked tumour samples and establish how they effect signal transduction, proliferation and cell death and if they are necessary or sufficient to promote cancer. Several novel mutations and translocations are available for study as the basis of a PhD- please see PhD Student section for more information.
Molecular Cytogenetics of Neuroblastoma – SNP arrays and targeted exome sequencing.
Developing targeted exome sequencing and other techniques for paediatric cancers
This includes the development of a cancer gene panel focused on childhood malignancies and RNA sequencing techniques to identify balanced translocations in paediatric cancer.
Proteomic Biomarkers in Acute Myeloid Leukaemia (AML)
We are using advanced proteomic techniques to characterise the proteins on the surface of cancer cells as a pathway to discover new biomarkers and drug targets.
Targeting IAPs in models of paediatric cancer
We are testing a new class of drug, alone and in combination, in preclinical models of cancer, including leukaemia.
Children’s Cancer Foundation Clinical Research Fellowship
Dr Seong Lin Khaw, a paediatric oncologist at The Royal Children's Hospital, is the recipient of a $1,370,000 fellowship co-funded by MCRI, the Children’s Cancer Foundation and the Victorian Cancer Agency. With the aid of this generous grant, Dr Khaw is well-placed to develop a ground-breaking research project which will seek to improve the effectiveness of treatment in children with very high risk acute lymphoblastic leukaemia (VHR-ALL) for whom standard-of-care therapy does not work.
- A phase I study of panobinostat in pediatric patients with refractory solid tumors, including CNS tumors. 2018
- Assessment of physical function in children with cancer: A systematic review. 2018
- Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma. 2018
- Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry. 2018
- Clinical trial participation by adolescents and young adults with cancer: A continued cause for concern? 2018
- Clinker: visualizing fusion genes detected in RNA-seq data. 2018
- DNA methylation profiling of genomic DNA isolated from urine in diabetic chronic kidney disease: A pilot study. 2018
- DNA methylation-based classification of central nervous system tumours. 2018
- Do Australian adolescents' and young adults' experiences of cancer care influence their quality of life? 2018
- Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1. 2018
- Experiences of Care of Adolescents and Young Adults with Cancer in Australia. 2018
- Exploring the feasibility and utility of exome-scale tumour sequencing in a clinical setting. 2018
- Factors influencing the documentation of fertility-related discussions for adolescents and young adults with cancer. 2018
- Factors influencing the provision of fertility counseling and impact on quality of life in adolescents and young adults with cancer. 2018
- MicroRNA-155 expression and function in AML: An evolving paradigm. 2018
- Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. 2018
- Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. 2018
- Paediatric anthracycline-induced cardiotoxicity: mechanisms, pharmacogenomics and pluripotent stem cell modelling. 2018
- Report of a bi-allelic truncating germline mutation in TP53. 2018
- Role of the β Common (βc) Family of Cytokines in Health and Disease. 2018
- Systematic review of pharmacogenomics and adverse drug reactions in paediatric oncology patients. 2018
- Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial. 2018
- Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. 2017
- Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. 2017
- Chemotherapy-related cardiotoxicity: are Australian practitioners missing the point? 2017
- Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood. 2017
- Disordered clusters of Bak dimers rupture mitochondria during apoptosis. 2017
- Dysregulation of BCL-2 family proteins by leukemia fusion genes. 2017
- External Validation of Six Pediatric Fever and Neutropenia Clinical Decision Rules. 2017
- High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression. 2017
- Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence. 2017
- Quantitative proteomic analysis of EZH2 inhibition in acute myeloid leukemia reveals the targets and pathways that precede the induction of cell death. 2017
- Risk assessment in paediatric glioma-Time to move on from the binary classification. 2017
- Use of ubiquitous, highly heterozygous copy number variants and digital droplet polymerase chain reaction to monitor chimerism after allogeneic haematopoietic stem cell transplantation. 2017
- Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins. 2016
- Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation. 2016
- Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia. 2016
- Pain assessment and management in paediatric oncology: a cross-sectional audit. 2016
- Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics. 2016
- The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. 2016
- The molecular relationships between apoptosis, autophagy and necroptosis. 2015
- ER stress does not cause up-regulation and activation of caspase-2 to initiate apoptosis 2014
- RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. 2014
- Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations 2013
- HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia 2013
- Hoxb8 regulates expression of microRNAs to control cell death and differentiation 2013
- Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival. 2013
- The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts. 2013
- Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death 2012
- Evaluation of microRNA expression in patient bone marrow aspirate slides. 2012
- An 11p15 imprinting centre region 2 deletion in a family with Beckwith Wiedemann syndrome provides insights into imprinting control at CDKN1C. 2011
- Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. 2011
- High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival. 2011
- Myeloid progenitor cells lacking p53 exhibit delayed up-regulation of Puma and prolonged survival after cytokine deprivation. 2010