A5001411382- CAR-T cell therapy research
- Sphingolipid Metabolism and Signaling
- Nanowire Synthesis and Applications
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Transgenic Plants and Applications
- Acute Myeloid Leukemia Research
- Cell Image Analysis Techniques
- Cellular transport and secretion
- Molecular Biology Techniques and Applications
- Glioma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Legionella and Acanthamoeba research
- Retinopathy of Prematurity Studies
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
- Fibroblast Growth Factor Research
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Heme Oxygenase-1 and Carbon Monoxide
Centre for Cancer Biology
2017-2024
University of South Australia
2017-2024
South Australia Pathology
2017-2024
Flinders University
2005-2013
Background Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers therapy, and the potential for severe toxicity. Effective treatments limited, 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but yet significantly benefit patients with glioblastoma. Early phase trials chimeric antigen receptor (CAR) T-cell in have demonstrated that this approach is...
Abstract Objectives Targeted immunotherapies such as chimeric antigen receptor (CAR)‐T cells are emerging attractive treatment options for glioblastoma, but rely on identification of a suitable tumor antigen. We validated new target fibroblast activation protein (FAP), by undertaking detailed expression study human samples. Methods Glioblastoma and normal tissues were assessed using immunostaining, supported analyses published transcriptomic datasets. Short‐term cultures glioma neural stem...
Inducing cell death by the sphingolipid ceramide is a potential anticancer strategy, but underlying mechanisms remain poorly defined. In this study, triggering an accumulation of in acute myeloid leukemia (AML) cells inhibition sphingosine kinase induced apoptotic integrated stress response (ISR) through protein R-mediated activation master transcription factor ATF4. This effect led to BH3-only Noxa and degradation prosurvival Mcl-1 on which AML are highly dependent for survival. Targeting...
Glioblastoma is one of the most common and lethal types primary brain tumor. Despite aggressive treatment with chemotherapy radiotherapy, tumor recurrence within 6–9 months common. To overcome this, more effective therapies targeting cancer cell stemness, invasion, metabolism, death resistance interactions cells their surrounding microenvironment are required. In this study, we performed a systematic review molecular mechanisms that drive glioblastoma progression, which led to identification...
Abstract DEPDC5 mutations have recently been shown to cause epilepsy in humans. Evidence from vitro studies has implicated as a negative regulator of mTORC1 during amino acid insufficiency part the GATOR1 complex. To investigate role vivo we generated null mouse model using targeted CRISPR mutagenesis. Depdc5 homozygotes display severe phenotypic defects between 12.5-15.5 dpc, including hypotrophy, anaemia, oedema, and cranial dysmorphology well blood lymphatic vascular defects....
Abstract Background Organoids are a reliable model used in the study of human brain development and under pathological conditions. However, current methods for organoid culture generate tissues that range from 0.5 to 2 mm size, which need be constantly agitated allow proper oxygenation. The conditions are, therefore, not suitable whole-brain live imaging, required developmental processes disease progression within physiologically relevant time frames (i.e. days, weeks, months). Results Here...
Glioblastoma is the most common and aggressive form of primary brain cancer, with no improvements in 5-year survival rate 4.6% over past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors chimeric antigen receptor T-cell therapy have prolonged patients other cancers undergone early-phase clinical evaluation glioblastoma patients. However, a major challenge for immunotherapy solid infiltration into tumours. This process mediated by chemokine-chemokine...
Abstract Objectives CAR‐T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) an ideal target antigen glioblastoma immunotherapy, with expression on both tumor and blood vessels. However, targeting FAP have never therapy glioblastoma. Methods generated CAR CD3ζ CD28 signalling domains tested the resulting their lytic activity cytokine secretion function in vitro (using...
While the two mammalian sphingosine kinases, SK1 and SK2, both catalyze generation of pro-survival 1-phosphate (S1P), their roles vary dependent on different subcellular localization. is generally found in cytoplasm or at plasma membrane where it can promote cell proliferation survival. SK2 be present appears to have a similar function SK1, but also localized nucleus, endoplasmic reticulum mitochondria mediates death. Although has been implicated cancer initiation progression, mechanisms...
The introduction of the proteasome inhibitor bortezomib into treatment regimens for myeloma has led to substantial improvement in patient survival. However, whilst elicits initial responses many patients, this haematological malignancy remains incurable due development acquired resistance. With other patients presenting with disease that is intrinsically resistant, it clear new therapeutic approaches are desperately required target bortezomib-resistant myeloma. We have previously shown...
Different inbred strains of rat differ in their susceptibility to oxygen-induced retinopathy (OIR), an animal model human prematurity. We examined gene expression Sprague–Dawley (susceptible) and Fischer 344 (resistant) neonatal rats after 3 days exposure cyclic hyperoxia or room air, using Affymetrix Genearrays. False discovery rate analysis was used identify differentially regulated genes. Such genes were then ranked by fold change submitted the online database, DAVID. The list returned...
Abstract Background Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers therapy, and the potential for severe toxicity. Effective treatments limited, 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but yet significantly benefit patients with glioblastoma. Early phase trials CAR-T cell have demonstrated that this approach is safe feasible, limited...
Abstract Objectives CAR-T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) an ideal target antigen glioblastoma immunotherapy, with expression on both tumor and blood vessels. However, targeting FAP have never therapy glioblastoma. Methods generated CAR CD3ζ CD28 signaling domains tested the resulting their lytic activity cytokine secretion function in vitro (using...
While bortezomib has significant benefits in multiple myeloma (MM) therapy, the disease remains incurable due to invariable development of resistance. This emphasises need for advanced models preclinical evaluation new therapeutic approaches bortezomib-resistant MM. Here, we describe an orthotopic syngeneic MM mouse model based on most well-characterised derived from spontaneous MM-forming C57BL/KaLwRij mice. Using 5TGM1 cells, report and characterise a robust that is well suited proteasome...