A5052652340- Glioma Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Neuroblastoma Research and Treatments
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- interferon and immune responses
- Chromatin Remodeling and Cancer
- Chemical Reactions and Isotopes
- Cancer Mechanisms and Therapy
- Brain Tumor Detection and Classification
- Immune Response and Inflammation
- Circular RNAs in diseases
- Cancer, Hypoxia, and Metabolism
- Hedgehog Signaling Pathway Studies
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Aldose Reductase and Taurine
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- Immune cells in cancer
- Kruppel-like factors research
- Genetic and Kidney Cyst Diseases
Monash University
2013-2024
Hudson Institute of Medical Research
2016-2024
Monash Institute of Medical Research
2013
The University of Tokyo
2004-2005
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine (DIPG), are the most lethal of childhood cancers. Palliative radiotherapy is only established treatment, with median patient survival 9 to 11 months. ONC201 a DRD2 antagonist and ClpP agonist that has shown preclinical emerging clinical efficacy in DMG. However, further work needed identify mechanisms response DIPGs treatment determine whether recurring genomic features influence response. Using systems-biological approach,...
Abstract Detection of microbial components such as lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) on macrophages induces a robust pro-inflammatory response that is dependent metabolic reprogramming. These innate changes have been compared to aerobic glycolysis in tumour cells. However, the mechanisms which TLR4 activation leads mitochondrial and glycolytic reprogramming are unknown. Here we show signalling cascade recruiting TRAF6 TBK-1, while TBK-1 phosphorylates STAT3 S727. Using...
Hedgehog (Hh) signaling regulates cell fate and self-renewal in development cancer. Canonical Hh is mediated by ligand binding to the receptor Patched (Ptch), which turn activates Gli-mediated transcription through Smoothened (Smo), molecular target of pathway inhibitors used as cancer therapeutics. Small lung (SCLC) a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that block capacity SCLC cells, lack activating mutations cast doubt...
Malignant rhabdoid tumor (MRT) and atypical teratoid tumors (ATRT) are rare aggressive undifferentiated primarily affecting the kidney CNS of infants young children. MRT almost exclusively characterized by homozygous deletion or inactivation chromatin remodeling gene SMARCB1 protein loss leads to direct impairment we have previously reported a role for this in histone acetylation. This provided rationale investigating therapeutic potential deactylase inhibitors (HDACi) MRT.Whereas HDACis...
Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that recombination by Cre instigates a robust antiviral response mammalian cells, independent legitimate loxP recombination. This is recruitment cytosolic sensor STING, concurrent with Cre-dependent damage and accumulation cytoplasmic Importantly, establish direct interplay between this...
Inhibition of activin signaling enhances the efficacy and safety platinum chemotherapy in lung adenocarcinoma models.
Different cell types possess different copies of mtDNA to support their specific requirements for cellular metabolism. Cell-specific copy numbers are established through cell-specific replication during differentiation. However, cancer cells trapped in a "pseudo-differentiated" state as they fail expand number. Global DNA methylation can regulate this process, induced demethylation promotes differentiation and expansion To determine the role that plays regulating tumorigenesis, we have...
TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement interferons associated with damaging hyper-inflammation found severe COVID-19 patients. The contribution TBK1/IKKε these unknown. Here we find...
Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis early-stage surgical specimens. Here we used endoscopic sampling paired primary and intrathoracic metastatic tumors from 11 patients to map inoperable with deep whole-genome sequencing. Intra-patient driver or targetable mutations was predominantly form copy number gain. Private mutation signatures, including patterns consistent defects homologous recombination, were highly variable both within between...
Signal transducer and activator of transcription 3 (STAT3) is a potent factor necessary for life whose activity corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its as until the discovery mitochondrial pool STAT3, which normal tissue function tumorigenesis. However, mechanism this remained elusive. This study uses immunoprecipitation mass spectrometry identify complex containing leucine-rich pentatricopeptide repeat (LRPPRC), SRA...
Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused capacity apoptosis in hematologic and lymphoid malignancies, often combination with conventional cytotoxic agents. In many cases, HDACi doses necessary effects result significant toxicity. Since osteosarcoma cells express markers terminal osteoblast differentiation...
STUDY HYPOTHESISThe mouse endometrium harbours stem/progenitor cells that express the stem cell marker telomerase reverse transcriptase (mTert).
Abstract Recognition of RNA fragments by Toll-like receptors (TLR) 7 and 8 is a key contributor to the initiation protective innate immune response against pathogens. A long-standing enigma how degradation products host RNAs, generated daily phagocytic clearance billions apoptotic cells, fail activate TLR7 TLR8 signalling 1 . Here, we report that select 2’-O-methyl (2’-Ome) guanosine as short 3 bases, including those derived from host-RNAs, are potent antagonists reduce sensing in vivo...
Hypermethylated-in-Cancer 1 (Hic1) is a tumor suppressor gene frequently inactivated by epigenetic silencing and loss-of-heterozygosity in broad range of cancers. Loss HIC1, sequence-specific zinc finger transcriptional repressor, results deregulation genes that promote malignant phenotype lineage-specific manner. In particular, upregulation the HIC1 target SIRT1, histone deacetylase, can growth inactivating TP53. An alternate line evidence suggests repair DNA double strand breaks through an...
Medulloblastoma is the most common malignant brain tumor in children and represents 20% of all pediatric central nervous system neoplasms. While advances surgery, radiation chemotherapy have improved overall survival, lifelong sequelae these treatments represent a major health care burden led to ongoing efforts find effective targeted treatments. There well-recognized male bias medulloblastoma diagnosis, although mechanism remains unknown. Herein, we identify sex-specific role for...
Ligand-dependent activation of Hedgehog (Hh) signaling in cancer occurs without mutations canonical pathway genes. Consequently, the genetic basis Hh adult solid tumors, such as small-cell lung (SCLC), is unknown. Here we show that combined inactivation Trp53 and Rb1, a defining feature SCLC, leads to hypersensitivity ligand vitro, during neural tube development vivo. This response associated with aberrant formation primary cilia, an organelle essential for through smoothened, transmembrane...
20α-Hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form 20α-dihydroprogesterone (20α-OHP). 20α-HSD is expressed in murine placenta, suggesting a role, yet unidentified, played by this enzyme during course pregnancy. To elucidate possible roles pregnancy, gene expression placenta was examined Northern blot analysis, and progestin (progesterone 20α-OHP) concentrations maternal fetal sera amniotic fluid were measured radioimmunoassay pregnant...
20α-Hydroxysteroid dehydrogenase (20α-HSD), which catalyzes the conversion of progesterone to its inactive form 20α-dihydroprogesterone, is expressed in murine placenta and has been suggested play roles maintaining pregnancy. To understand role 20α-HSD during pregnancy goat, as a first step, cloning sequencing cDNA were performed. The full nucleotide sequence was determined on samples obtained from corpus luteum at luteal phase estrous cycle late by RT-PCR 3' 5' RACE systems. Cloned...
Atypical teratoid rhabdoid tumour (ATRT) is a rare but highly aggressive undifferentiated solid arising in the central nervous system and predominantly affecting infants young children. ATRT exclusively characterized by inactivation of SMARCB1, member SWI/SNF chromatin remodelling complex that essential for regulation large sets genes required normal development differentiation. Histone deacetylase inhibitors (HDACi) are promising anticancer therapy able to mimic acetylation functions...
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<p>All Supplementary Tables</p>
<p>All Supplementary Figures and their captions.</p>
<p>All Supplementary Tables</p>