A5068776486- Glioma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Renal and related cancers
- Circular RNAs in diseases
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- Chromatin Remodeling and Cancer
- Cancer-related molecular mechanisms research
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Melanoma and MAPK Pathways
- Nanoparticle-Based Drug Delivery
- Mass Spectrometry Techniques and Applications
- Ferroptosis and cancer prognosis
The University of Queensland
2013-2023
Translational Research Institute
2020-2023
The Kids Research Institute Australia
2011-2012
The University of Western Australia
2011-2012
Abstract Purpose: Bioinformatics analysis followed by in vivo studies patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis. Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was potential novel targets. The top hit this validated using PDX...
Basal cell carcinoma (BCC) of the skin is most common form human cancer, with more than 90% tumours presenting clear genetic activation Hedgehog pathway. However, polygenic risk factors affecting mechanisms such as DNA repair and cycle checkpoints or which modulate tumour microenvironment host immune system play significant roles in determining whether mutations culminate BCC development. We set out to define background that a role influencing susceptibility via promoting suppressing effects...
Significance Medulloblastoma is a common malignant pediatric brain tumor. Gene expression data have indicated that the tumors fall into four molecular subgroups, “Wnt,” “Hedgehog,” “group 3,” and 4.” With exception of Hedgehog subgroup, few functional exist defining key pathways driving tumor growth. Using transposon mutagenesis approach, we identified genes functionally cooperate with signalling to promote tumorigenesis in Ptch1 mouse model medulloblastoma. Surprisingly, were able...
Cerebellar ataxias are severe neurodegenerative disorders with an early onset and progressive inexorable course of the disease. Here, we report a single point mutation in gene encoding Elongator complex subunit 6 causing Purkinje neuron degeneration ataxia-like phenotype mutant wobbly mouse. This destabilizes compromises its function translation regulation, leading to protein misfolding, proteotoxic stress, eventual neuronal death. In addition, show that substantial microgliosis is triggered...
Abstract Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders characterized by substantial impairment in intellectual adaptive functioning, with their genetic molecular basis remaining largely unknown. Here, we identify biallelic variants gene encoding one of Elongator complex subunits, ELP2, patients ID ASD. Modelling mice recapitulates patient features, brain imaging tractography analysis revealing microcephaly, loss white matter...
Abstract Background Medulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single-cell transcriptome studies have defined cellular states underlying each MB subgroup; however, spatial organisation these diverse cell how this impacts response to therapy remains determined. Methods Here, we used spatially resolved transcriptomics define diversity within sonic hedgehog (SHH) patient-derived...
Medulloblastoma (MB) is the most common malignant brain tumor in children and a leading cause of cancer-related mortality morbidity. Several molecular sub-types MB have been identified, suggesting they may arise from distinct cells origin. Data animal models indicate that some multipotent cerebellar neural stem (NSCs). Hence, microRNA (miRNA) expression profiles primary samples were compared to CD133+ NSCs, aiming identify deregulated miRNAs involved pathogenesis. Expression profiling 662...
The clinical translation of new nanoparticle-based therapies for high-grade glioma (HGG) remains extremely poor. This has partly been due to the lack suitable preclinical mouse models capable replicating complex characteristics recurrent HGG (rHGG), namely heterogeneous structural and functional blood-brain barrier (BBB). goal this study is compare tumor BBB rHGG with two different HGG, ubiquitously used U87 cell line xenograft model a patient-derived WK1 model, in order assess their...
High-grade glioma (HGG) remains a recalcitrant clinical problem despite many decades of research. A major challenge in improving prognosis is the inability current therapeutic strategies to address clinically significant burden infiltrating tumor cells that extend beyond margins primary mass. Such cannot be surgically excised nor efficiently targeted by radiation therapy. Therapeutic targeting this cell population significantly hampered presence an intact blood-brain barrier (BBB). In study,...
Medulloblastoma (MB) is the most common type of malignant childhood brain tumour. Although deregulated microRNA (miRNA) expression has been linked to MB pathogenesis, selection appropriate candidate endogenous control (EC) reference genes for miRNA profiling studies not systematically addressed. In this study we utilised reverse transcriptase quantitative PCR (RT-qPCR) identify EC accurate normalisation data in primary human specimens and neural stem cells.Expression 662 miRNAs six small...
Novel targeted therapies for children diagnosed with medulloblastoma (MB), the most common malignant pediatric brain tumor, are urgently required. A major hurdle in development of effective is impaired delivery systemic to tumor cells due a specialized endothelial blood-brain barrier (BBB). Accordingly, integrity BBB an essential consideration any preclinical model used assessing novel therapeutics. This study sought assess functional several mouse models MB.Dynamic contrast enhancement...
Medulloblastoma (MB) is the most common malignant paediatric brain tumour and a leading cause of cancer-related mortality morbidity. Existing treatment protocols are aggressive in nature resulting significant neurological, intellectual physical disabilities for children undergoing treatment. Thus, there an urgent need improved, targeted therapies that minimize these harmful side effects. We identified candidate drugs MB using network-based systems-pharmacogenomics approach: based on results...
Abstract Background Medulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single cell transcriptome studies have defined cellular states underlying each MB subgroup, however spatial organisation these diverse how this impacts response to therapy remains determined. Methods Here, we used spatially resolved transcriptomics define diversity within sonic hedgehog (SHH) patient-derived model...
Abstract Medulloblastoma is the most common malignant pediatric brain tumor and there an urgent need for molecularly targeted subgroup-specific therapies. The stem cell factor SOX9, has been proposed as a potential therapeutic target treatment of Sonic Hedgehog medulloblastoma (SHH-MB) subgroup tumors, given its role downstream signaling in functionally promoting SHH-MB metastasis resistance. However, functional requirement SOX9 genesis remains to be determined. Here we report previously...
Abstract Cancer responses to drug treatment are highly heterogeneous. We postulate that spatial determinants in the tumour play a critical role cancer therapy outcomes. Here, we will present two transcriptomics studies on immunotherapy and chemotherapy. Immune checkpoint inhibitors (ICI) used treat recurrent metastatic oropharyngeal squamous cell carcinomas (OPSCC). Unfortunately, less than 30% of patients benefit from this therapy. Thus, performed (ST) in-situ multiprotein detection...
<p>Figure S1 shows the delineation of tumor in MRI images.</p>
<p>Legends describing the supplementary figures</p>
<p>Figure S2 shows the investigation of BBB integrity in intracranial Med-211FH tumors using MRI.</p>
<div>Abstract<p><b>Purpose:</b> Bioinformatics analysis followed by <i>in vivo</i> studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 <i>MYC</i>-amplified tumors that have the worst clinical prognosis.</p><p><b>Experimental Design:</b> A protein interaction network derived from a...
<div>Abstract<p><b>Purpose:</b> Bioinformatics analysis followed by <i>in vivo</i> studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 <i>MYC</i>-amplified tumors that have the worst clinical prognosis.</p><p><b>Experimental Design:</b> A protein interaction network derived from a...
<p>Legends describing the supplementary figures</p>