Honorary Research Associate
Professor Johns was appointed Head of the Telethon Kids Institute Cancer Centre in 2017. He brings with him a strong track record in translational research and extensive national and international collaborative networks, including important relationships with major pharmaceutical companies. He has maintained a stable and well-funded laboratory for over 20 years and has supervised and mentored many students and early career researchers with diverse interests and backgrounds.
Professor Johns and the Cancer Centre’s team of talented researchers, clinicians and students are committed to improving the outcomes for children with cancer and expanding the Cancer Centre’s global profile and impact through cutting edge research.
Career history
After completing a PhD in 1993 at Monash University in the Department of Biochemistry, Professor Johns joined La Trobe University’s Neuroimmunology Laboratory as a Postdoctoral Fellow. During his time there, he helped develop a new model of multiple sclerosis that remains in use around the world today. In 1998, Professor Johns commenced as a Research Fellow at the Ludwig Institute for Cancer Research and went on to establish the Oncogenic Signalling Laboratory. The focus of his laboratory was the development of antibodies that target receptors on the surface of cancer cells important to their survival and growth. In particular, Professor Johns played a key role in the development of mAb 806 (now known as ABT-414), a novel antibody that targets the epidermal growth factor receptor (EGFR) and is currently in late stage clinical trials.
Professor Johns moved his oncogenic signalling laboratory to the Hudson Institute of Medical Research in 2008, and he was based there until his recent appointment at the Telethon Kids Institute. In Perth, his laboratory continues to analyse the key signalling pathways associated with the growth of glioma, an aggressive and generally lethal type of brain cancer, to guide the development of new drugs and therapeutic antibodies. Reflecting his strong track record in translational research, Professor Johns has had key roles in many clinical trials, including the Australian CABARET trial for patients with recurrent high-grade glioma. Recently, he extended his expertise in cancer therapy to developing new treatments for ectopic pregnancy, a life-threatening condition in which the foetus is implanted outside the uterus. These new treatments are also now in late phase clinical trials. Professor Johns has received funding from some of the world’s biggest pharmaceutical and biotech companies, including Pfizer, Roche and Amgen, for preclinical and clinical testing of drug candidates.
Professor Johns has worked hard to bring the Australian brain cancer research community together and accelerate the drug translation process. In 2012, he founded the Brain Cancer Discovery Collaborative, an Australia-wide consortium of researchers and clinicians dedicated to ensuring that promising therapeutic discoveries are translated into the clinic for the treatment of patients with brain cancer.
His current research interests include the following:
- understanding the biology and intracellular signalling properties of EGFR and other receptor tyrosine kinases in high-grade glioma
- identifying mechanisms of resistance to EGFR-targeted therapies
- characterizing the role of ErbB4 in high-grade glioma
- evaluating CT-179, a new drug that targets OLIG2, a transcription factor that has a central role in many brain cancers
- determining whether ion-channels influence the response to brain cancer therapeutics
Find Professor Johns on ORCID.
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Projects
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Publications
October 2023
From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress
Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need.
Children's Cancers Published research Brain Tumour Research Subsite: CancerJuly 2023A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence
Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects.
Children's Cancers Published research Subsite: Cancer Sarcoma Translational Research Translational GeneticsMarch 2023Clinical Trials in the Brain Tumour Population: Challenges and Strategies for the Future
This review identifies challenges and barriers to successful development of drugs in neuro-oncology trials at the preclinical, clinical and translational stages that we believe has contributed to poor outcomes for patients over the last 30 years.
Children's Cancers Published research Oncogenic Signalling LaboratoryNovember 2022Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?
Glioblastoma is the most common form of high-grade glioma in adults and has a poor survival rate with very limited treatment options. There have been no significant advancements in glioblastoma treatment in over 30 years. Epidermal growth factor receptor is upregulated in most glioblastoma tumours and, therefore, has been a drug target in recent targeted therapy clinical trials.
Children's Cancers Published research Brain Tumour Research Sarcoma Translational Research Cancer Immunology and BiologySeptember 2022Potassium Ion Channels in Malignant Central Nervous System Cancers
Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance.
Children's Cancers Published research Sarcoma Translational Research Cancer Immunology and BiologyAugust 2022ErbB4 in the brain: Focus on high grade glioma
The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTKs) consists of EGFR, ErbB2, ErbB3, and ErbB4. These receptors play key roles in cell proliferation, angiogenesis, cell migration, and in some cases, tumor promotion.
Children's Cancers Published research Subsite: Cancer Cancer Immunology and BiologyDecember 2021LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study
Introduction Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM.
Published research Cancer Immunology and BiologyApril 2021Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells
Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins.
Children's Cancers Published research Cancer Immunology and BiologyJanuary 2021Small-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: CancerMarch 2020MK2 inhibition induces p53-dependent senescence in glioblastoma cells
In response to DNA damaging chemotherapy, targeting MK2 in p53-mutated cells produces a phenotype that is distinct from the p53-deficient phenotype
Children's Cancers Published research Cancer Immunology and BiologyFebruary 2020Simultaneous Targeting of DNA Replication and Homologous Recombination in Glioblastoma with a Polyether Ionophore
Our findings highlight the potential of salinomycin to induce DNA lesions and inhibit homologous recombination to greatly enhance the effect of radiotherapy
Children's Cancers Published research Cancer Immunology and BiologyDecember 2019The dystroglycan receptor maintains glioma stem cells in the vascular niche
These findings reveal a central role of the DG receptor, not only as a structural element, but also as a critical factor promoting mesenchymal-like GBM
Children's Cancers Published research Cancer Immunology and BiologyDecember 2019Whole genome and biomarker analysis of patients with recurrent glioblastoma on bevacizumab: A subset analysis of the CABARET trial.
Whole genome sequencing of poor and exceptional survivors identified a gain in Chromosome 19 that was exclusive to the exceptional survivors
Children's Cancers Published research Cancer Immunology and BiologyApril 2019Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma
We discovered a previously unknown major resistance mechanism in glioma in that most EGFR domain III-targeting antibodies do not neutralize EGFRvIII
Children's Cancers Published research Brain Tumour Research Cancer Immunology and BiologyMarch 2019A reference collection of patient-derived cell line and xenograft models of proneural, classical and mesenchymal glioblastoma
We present a curated panel of 12 readily-usable, cell lines representing the spectrum of molecular subtypes of IDH-wildtype glioblastoma
Children's Cancers Published research Cancer Immunology and BiologySeptember 2018PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein
A novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis
Children's Cancers Published research Cancer Immunology and BiologySeptember 2018PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein
Our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis
Children's Cancers Published research Cancer Immunology and BiologyAugust 2018Differential Sensitivity of Human Hepatocellular Carcinoma Xenografts to an IGF-II Neutralizing Antibody May Involve Activated STAT3
These findings implicate the activation of STAT3 as one pathway that may mediate resistance to IGF-II-targeted therapy in HCC
Published research Cancer Immunology and BiologyAugust 2018Changes in cell morphology guide identification of tubulin as the off-target for protein kinase inhibitors
Early changes in cell morphology upon treatments are a strong indication that the inhibitor is directly targeting tubulin
Published research Cancer Immunology and BiologyJuly 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 Cancer Immunology and BiologyJuly 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 Cancer Immunology and BiologyMarch 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 Cancer Immunology and Biology