Co-Head, Brain Tumour Research
MBChB FRACP PhD
Dr Nick Gottardo is Co-Head of the Institute's Brain Tumour Research Team and a Consultant Paediatric Oncologist/Neuro-Oncologist and Head of Department of Paediatric Oncology and Haematology at Princess Margaret Hospital for Children. Dr Gottardo is also an Adjunct Associate Clinical Professor at the University of Western Australia and a Fellow of the Royal Australasian College of Physicians (RACP).
Dr Gottardo is driven by his belief that it's unacceptable for children to die from brain tumours. His research interests include developing laboratory models of brain tumours, testing new therapies using these models and identifying areas of weaknesses in the tumours that might be suitable drug targets.
Dr Gottardo's medical career began at Leeds University with a Bachelor of Medicine, Bachelor of Surgery/Chirurgery. He worked for two and a half years as a doctor in the UK, before heading to Australia in 1996, where he took up a position at Princess Margaret Hospital for Children and began a PhD at Telethon Kids. After completing his PhD, Dr Gottardo headed to St Jude Children's Research Hospital in Memphis, USA, one of the world's premier childhood cancer institutes. He spent three years at St Jude as a post-doctoral brain tumour fellow and gained extensive experience in the laboratory in brain tumour model generation, preclinical testing and brain cancer cell biology, as well as expertise in the management of children with brain tumours in the clinic. In 2008 he received the International Symposium Paediatric Neuro-Oncology (ISPNO) Young Investigator award for scientific excellence. Dr Gottardo returned to Perth Australia in 2008 as a Consultant Paediatric Oncologist/Neuro-Oncologist and established the Brain Tumour Research Programme at the Telethon Kids Institute. In 2012 he was awarded the Raine Clinician Research Fellowship and in 2016 the Cancer Council Western Australia Research Fellowship.
In his clinical capacity Dr Gottardo is the Deputy Chair of the Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG) and Chair of their Central Nervous System (CNS)Tumours Subgroup, and a Board member of the Australian Children’s Cancer Therapy (ACCT) group. He is also a member of the international North American based Children’s Oncology Group (COG) CNS Tumour Committee and leads the COG’s upfront clinical trial for patients with WNT-driven medulloblastoma. He collaborates extensively both nationally and internationally; he is a founding member of the Brain Cancer Discovery Collaborative (BCDC) – a collaborative network consisting of the best brain cancer scientists and clinicians across Australia and a member of the International Medulloblastoma Working Group.
Find Dr Gottardo on ORCID.
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Projects
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Publications
January 2021
Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma
Medulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.
Published research Academic Biostatistics Brain Tumour Research Subsite: CancerJanuary 2021Assessment of Cannabidiol and Delta9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma
Children with medulloblastoma and ependymoma are treated with a multidisciplinary approach that incorporates surgery, radiotherapy, and chemotherapy; however, overall survival rates for patients with high-risk disease remain unsatisfactory. Data indicate that plant-derived cannabinoids are effective against adult glioblastoma; however, preclinical evidence supporting their use in pediatric brain cancers is lacking. Here we investigated the potential role for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in medulloblastoma and ependymoma. Dose-dependent cytotoxicity of medulloblastoma and ependymoma cells was induced by THC and CBD in vitro, and a synergistic reduction in viability was observed when both drugs were combined.
Children's Cancers Published research Subsite: CancerMarch 2021A surveillance clinic for children and adolescents with, or at risk of, hereditary cancer predisposition syndromes
Hereditary cancer predisposition syndromes (HCPS) account for at least 10% of paediatric cancers.1 Li‐Fraumeni syndrome (LFS) is a dominant HCPS caused by mutations in the TP53 gene and is associated with an 80–90% lifetime risk of cancer, commencing in infancy.2 Children of affected individuals are at 50% risk of inheriting the family mutation.
Children's Cancers Published research Brain Tumour Research Subsite: CancerApril 2021Veliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma
Medulloblastoma is the most common malignant childhood brain tumor, and 5-year overall survival rates are as low as 40% depending on molecular subtype, with new therapies critically important. As radiotherapy and chemotherapy act through the induction of DNA damage, the sensitization of cancer cells through the inhibition of DNA damage repair pathways is a potential therapeutic strategy.
Children's Cancers Published research Brain Tumour Research Subsite: CancerApril 2021Malignant Melanoma in Children and Adolescents Treated in Pediatric Oncology Centers: An Australian and New Zealand Children’s Oncology Group (ANZCHOG) Study
Unlike adults, malignant melanoma in children and adolescents is rare. In adult melanoma, significant progress in understanding tumor biology and new treatments, including targeted therapies and immunotherapy have markedly improved overall survival. In sharp contrast, there is a paucity of data on the biology and clinical behavior of pediatric melanoma. We report a national case series of all pediatric and adolescent malignant melanoma presenting to ANZCHOG Childhood Cancer Centers in Australia and New Zealand.
Children's Cancers Published research Brain Tumour Research Subsite: CancerJune 2021Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma
Medulloblastoma is the most common malignant paediatric brain tumour and a leading cause of cancer-related mortality and morbidity. Existing treatment protocols are aggressive in nature resulting in significant neurological, intellectual and physical disabilities for the children undergoing treatment. Thus, there is an urgent need for improved, targeted therapies that minimize these harmful side effects.
Children's Cancers Published research Brain Tumour Research Subsite: CancerOctober 2021Incidence and survival for childhood central nervous system tumours in Australia, 1983–2016
To investigate incidence and survival of childhood tumours of the central nervous system (CNS) by histological subtype, tumour behaviour and tumour grade. Methods: National, population-based data on all children under 15 years old diagnosed with a CNS tumour between 1983 and 2016 were sourced from the Australian Childhood Cancer Registry. Incidence rate trends were calculated using Joinpoint regression.
Children's Cancers Published research Brain Tumour Research Subsite: CancerNovember 2020Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer
The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations.
Children's Cancers Published research Brain Tumour Research Subsite: CancerApril 2020Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplant
This study provides evidence to support annual inactivated influenza vaccine administration to children following allogeneic haematopoietic stem cell transplant
Children's Cancers Published research Academic Biostatistics Infectious Diseases Epidemiology Vaccine Trials Group Brain Tumour Research Leukaemia Translational ResearchApril 2020Germline Elongator mutations in Sonic Hedgehog medulloblastoma
Genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers
Children's Cancers Published research Brain Tumour ResearchJanuary 2020'Walking their walk': Reducing conflict between families of ill children and the medical profession
I review recent high-profile court cases to underscore the changing landscape of conflict and the central role that the media (and social media in particular) can play
Published research Brain Tumour ResearchJanuary 2019International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma
This multi-center study provides valuable information on the success rate of establishing patient-derived pre-clinical models of diffuse intrinsic pontine glioma
Children's Cancers Published research Brain Tumour ResearchJanuary 2019Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma
Bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity
Children's Cancers Published research Brain Tumour ResearchApril 2019The Australian and New Zealand Children's Haematology/Oncology Group Biobanking Network
The ANZCHOG-BN is a new biobank network in Australasia that was developed to improve and streamline access to high-quality pediatric and AYA cancer biospecimens
Children's Cancers Published research Brain Tumour ResearchApril 2019The Australian and New Zealand Children's Haematology/Oncology Group Biobanking Network
The ANZCHOG-BN was developed to improve and streamline access to high quality pediatric and adolescent/young adult cancer biospecimens for cancer research
Children's Cancers Published research Brain Tumour ResearchAugust 2019Challenges to curing primary brain tumours
The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment in brain tumours
Children's Cancers Published research Brain Tumour ResearchNovember 2018Diffuse Intrinsic Pontine Glioma
This chapter summarizes recent advances in diffuse intrinsic pontine glioma and potential novel therapies
Children's Cancers Published research Brain Tumour ResearchAugust 2018Exercise training improves vascular function and secondary health measures in survivors of pediatric oncology related cerebral insult
This study demonstrates that exercise is achievable and has positive effects on vascular function, submaximal fitness, local strength and physical activity in a population of AYA survivors of pediatric oncology related cerebral insult
Children's Cancers Brain Tumour ResearchJuly 2018Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response
The functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target
Children's Cancers Published research Brain Tumour Research Oncogenic Signalling LaboratoryJuly 2018Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma
We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with diffuse intrinsic pontine glioma
Children's Cancers Published research Brain Tumour ResearchJuly 2018Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response
Despite low ERBB4 mRNA in glioblastoma, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target
Children's Cancers Published research Brain Tumour Research Oncogenic Signalling LaboratoryJuly 2018Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry
These findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma
Children's Cancers Published research Brain Tumour ResearchJuly 2018"Pre-emptive strike"-the case for early treatment of hepatic sinusoidal obstruction syndrome with defibrotide
We describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment
Published research Brain Tumour ResearchJune 2018Metabolic and Psychological Impact of a Pragmatic Exercise Intervention Program in Adolescent and Young Adult Survivors of Pediatric Cancer-Related Cerebral Insult
Adolescent and young adult survivors of childhood brain tumors and cranial irradiation should be screened for metabolic and psychological well-being
Children's Cancers Published research Brain Tumour ResearchApril 2018Unusual paediatric spinal myxopapillary ependymomas: Unique molecular entities or pathological variations on a theme?
We describe two unusual cases of MPE and use DNA methylation analyses to compare their signatures to try and distinguish if these represent a unique subset.
Published research Brain Tumour ResearchMarch 2018DNA methylation-based classification of central nervous system tumours
Here we present an approach for the DNA methylation-based classification of central nervous system tumors across all groups and demonstrate its application.
Published research Brain Tumour ResearchMarch 2018A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors
Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors.
Published research Brain Tumour Research Oncogenic Signalling LaboratoryJanuary 2018Medulloblastoma
Medulloblastoma is a highly malignant small round blue cell tumor of the posterior fossa
Children's Cancers Published research Brain Tumour ResearchApril 2017A novel technique of serial biopsy in mouse brain tumour models
Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model
Children's Cancers Published research Brain Tumour ResearchApril 2017Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data
Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors.
Children's Cancers Published research Brain Tumour ResearchMay 2017A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors
In this. i study the MTD and RP2D, safety, PK, and preliminary activity of single-agent ribociclib were investigated in patients with neuroblastoma.
Children's Cancers Published research Brain Tumour ResearchSeptember 2017Contemporary survival endpoints: An international diffuse intrinsic pontine glioma registry study
This study defines PFS and OS, and is the first describe post-progression survival in a large cohort of children with DIPG.
Children's Cancers Published research Brain Tumour ResearchSeptember 2017Irreversible growth plate fusions in children with medulloblastoma treated with a targeted hedgehog pathway inhibitor
We report on 3 children treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy.
Children's Cancers Published research Brain Tumour ResearchOctober 2016Recurrent MET fusion genes represent a drug target in pediatric glioblastoma
We identified previously unidentified gene fusions involving the MET oncogene in pediatric glioblastoma
Children's Cancers Published research Brain Tumour ResearchFebruary 2016Immunogenicity and clinical effectiveness of the trivalent inactivated influenza vaccine in immunocompromised children undergoing treatment for cancer
The trivalent inactivated influenza vaccine is safe, immunogenic, provides clinical protection and should be administered annually to immunosuppressed children receiving treatment for cancer
Children's Cancers Published research Academic Biostatistics Vaccine Trials Group Brain Tumour Research Leukaemia Translational ResearchNovember 2015Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiation
This study investigates the different patterns of relapse in patients with central nervous system mixed malignant germ cell tumors - treated with chemotherapy.
Children's Cancers Published research Brain Tumour ResearchAugust 2015Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape.
This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors.
Children's Cancers Published research Brain Tumour ResearchJune 2015Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication
We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols to determine...
Children's Cancers Published research Brain Tumour ResearchJune 2015Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiation
This study investigated the relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated with chemotherapy-only
Children's Cancers Published research Brain Tumour ResearchMarch 2015Folate pathway gene polymorphisms and risk of childhood brain tumors: Results from an Australian case-control study
Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate...
Children's Cancers Published research Academic Biostatistics Alcohol and Pregnancy and FASD Research Brain Tumour Research Cancer EpidemiologyFebruary 2015Novel peptide-based drugs for the treatment of sonic hedgehog-dependent medulloblastoma
Medulloblastoma, the most common pediatric malignant brain tumor, consists of at least four distinct molecular subgroups.
Children's Cancers Published research Brain Tumour ResearchFebruary 2015Rare childhood cancers—an increasing entity requiring the need for global consensus and collaboration
Rare childhood cancers have not benefited to the same extent from the gains that have been made for their frequently occurring counterparts.
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchNovember 2014Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis
Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality.
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchOctober 2014Germ-line and somatic DICER1 mutations in pineoblastoma
This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility...
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchApril 2014Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent receptor dimerization and display enhanced sensitivity
Epidermal growth factor receptor (EGFR) is over-expressed in many brain tumors. This paper examines mutations the EGFR that make the cell it is produced in...
Children's Cancers Published research Brain Tumour ResearchApril 2014The evolution of clinical trials for infant acute lymphoblastic leukemia
Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has...
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchNovember 2013Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group
Medulloblastoma is curable in approximately 70 % of patients. Over the past decade, progress in improving survival using conventional therapies has stalled...
Children's Cancers Published research Brain Tumour ResearchSeptember 2013Morbidity in survivors of child and adolescent meningioma
Given the paucity of data concerning long-term outcome, the authors undertook a meta-analysis to analyze morbidity in survivors of this disease.
Published research Academic Biostatistics Brain Tumour ResearchApril 2013Bacillus Cereus Bacteremia and Multiple Brain Abscesses During Acute Lymphoblastic Leukemia Induction Therapy
Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis,...
Children's Cancers Published research Infectious Diseases Vaccine Trials Group Brain Tumour ResearchMarch 2013Efficacy of acute myeloid leukemia therapy without stem-cell transplantation in a child with blastic plasmacytoid dendritic cell neoplasm
Our case demonstrates that AML therapy, without HSCT, can be sufficient to treat this rare disease in children.
Children's Cancers Published research Brain Tumour ResearchNovember 2012Maternal Use of Folic Acid and Other Supplements and Risk of Childhood Brain Tumors
Interest in a possible protective effect of maternal vitamin use before or during pregnancy against childhood brain tumors (CBT) and other childhood cancers...
Children's Cancers Published research Academic Biostatistics Alcohol and Pregnancy and FASD Research Brain Tumour Research Cancer EpidemiologySeptember 2012Chemotherapy increases amenability of surgical resection in congenital glioblastoma
Brain tumors presenting in infancy, especially during the first 6 months of life.
Children's Cancers Published research Brain Tumour ResearchJuly 2012Idiosyncratic nature of voriconazole photosensitivity in children undergoing cancer therapy
In adults, the unpredictability of voriconazole pharmacokinetics, particularly in those patients receiving chemotherapy, is well recognised. A paucity of...
Children's Cancers Published research Vaccine Trials Group Brain Tumour ResearchMarch 2012Interactions between acute lymphoblastic leukemia and bone marrow stromal cells influence response to therapy
To identify links between drug resistance and gene deregulation we used oligonucleotide microarray technology.
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchNovember 2011Meningiomas in children and adolescents: a meta-analysis of individual patient data
The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined...
Children's Cancers Published research Brain Tumour ResearchSeptember 2011Integrated Analysis of miRNA and mRNA Expression in Childhood Medulloblastoma Compared with Neural Stem Cells
Medulloblastoma (MB) is the most common malignant brain tumor in children and a leading cause of cancer-related mortality and morbidity.
Children's Cancers Published research Brain Tumour ResearchSeptember 2011Integrated analysis of miRNA and mRNA expression in childhood Medulloblastoma
Medulloblastoma (MB) is the most common malignant brain tumor in children and a leading cause of cancer-related mortality and morbidity.
Children's Cancers Published research Brain Tumour ResearchSeptember 2011Interactions between acute lymphoblastic leukemia and bone marrow stromal cells influence response to therapy
The cure rate for pediatric patients with B precursor acute lymphoblastic leukemia (pre-B ALL) is steadily improving, however relapses do occur despite...
Children's Cancers Published research Brain Tumour Research Leukaemia Translational ResearchJanuary 2011Pediatric meningioma: Current approaches and future direction
With improvement in leukemia therapy, central nervous system (CNS) tumors are the leading cause of cancer mortality in children and the most expensive...
Children's Cancers Published research Brain Tumour ResearchMarch 2010MEIS proteins as partners of the TLX1/HOX11 oncoprotein
Aberrant expression of the TLX1/HOX11 proto-oncogene is associated with a significant subset of T-cell acute lymphoblastic leukemias...
Children's Cancers Published research Brain Tumour Research Leukaemia Translational Research -
Education and Qualifications
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Awards/Honours