A5079399767- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Immune Response and Inflammation
- Acute Myeloid Leukemia Research
- Lung Cancer Research Studies
- Protein Tyrosine Phosphatases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Hedgehog Signaling Pathway Studies
- Cancer Mechanisms and Therapy
- Neuroblastoma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- NF-κB Signaling Pathways
- Genetics and Neurodevelopmental Disorders
- Whipple's Disease and Interleukins
Monash University
2015-2025
Hudson Institute of Medical Research
2016-2025
Institute of Neurobiology
2020
Hudson Institute
2020
University of York
2015
California Western School of Law
2014
New York University
2007-2014
NYU Langone Health
2008-2013
Monash Institute of Medical Research
2013
Columbia University Irving Medical Center
2012
Ras, STAT3, and Transformation The STAT (signal transducer activator of transcription) proteins are activated in response to receptor stimulation act the nucleus regulate gene expression. Gough et al. (p. 1713 ) found that STAT3 functioned transformation cells by oncogene Ras. However, this activity was maintained mutants fail activate transcription. Instead, active appeared be associated with mitochondria. Furthermore, modified targeted mitochondria promoted mitochondrial function disrupted...
Abstract Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, critical for IL-10-induced modulation mitochondrial dynamics oxidative respiration. Mechanistically, catalytic activity presence Arg2 crucial phosphorylation. We further mediates this process by increasing complex II (succinate dehydrogenase)....
The pro-oncogenic transcription factor STAT3 is constitutively activated in a wide variety of tumours that often become addicted to its activity, but no unifying view core function determining this widespread STAT3-dependence has yet emerged. We show here active acts as master regulator cell metabolism, inducing aerobic glycolysis and down-regulating mitochondrial activity both primary fibroblasts STAT3-dependent tumour lines. As result, cells are protected from apoptosis senescence while...
Autocrine priming of cells by small quantities constitutively produced type I interferon (IFN) is a well-known phenomenon. In the absence IFN priming, display attenuated responses to other cytokines, such as anti-viral protection in response IFNγ. This phenomenon was proposed be because IFNα/β receptor1 (IFNAR1) component IFNγ receptor (IFNGR), but our new data are more consistent with previously model indicating that regulated expression STAT1 may also play critical role process. Initially,...
Activating mutations in the RasGTPases are most common oncogenic lesions human cancer. Similarly, elevated STAT3 expression and/or phosphorylation observed majority of cancers. We recently found that activated Ras requires a mitochondrial rather than nuclear activity to support cellular transformation. This was supported by on serine 727 (S727) carboxyl-terminus STAT3. In this study we show H-Ras oncoprotein engages MEK-ERK pathway drive S727, while phosphoinositide 3-kinase (PI3K) and mTOR...
Abstract Mitochondrial DNA (mtDNA) copy number is strictly regulated during differentiation so that cells with a high requirement for ATP generated through oxidative phosphorylation have mtDNA number, whereas those low few copies. Using immunoprecipitation of methylation on 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), which distinguish between de nov o demethylation, respectively, we set out to determine whether at exon 2 the human mtDNA-specific polymerase (DNA gamma A ( POLGA...
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...
Small cell lung cancer (SCLC) is an aggressive neuroendocrine with appalling overall survival of less than 5% (Zimmerman et al. J Thor Oncol 14:768-83, 2019). Patients typically respond to front line platinum-based doublet chemotherapy, but almost universally relapse drug resistant disease. Elevated MYC expression common in SCLC and has been associated platinum resistance. This study evaluates the capacity drive resistance through screening identifies a capable reducing overcoming following...
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the unresponsive or able to adapt therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested activity THZ1,...
Increased production of mitochondrion-derived reactive oxygen species (ROS) is characteristic a metabolic shift observed during malignant transformation. While the exact sources and roles ROS in tumorigenesis remain to be defined, it has become clear that maintaining redox balance critical for cancer cell proliferation survival and, as such, may represent vulnerability can exploited therapeutically. STAT3, latent cytosolic transcription factor activated by diverse cytokines growth factors,...
Toll-like receptors (TLRs) play critical roles in host defense after recognition of conserved microbial- and host-derived components, their dysregulation is a common feature various inflammation-associated cancers, including gastric cancer (GC). Despite the recent that metabolic reprogramming hallmark cancer, molecular effectors altered metabolism during tumorigenesis remain unclear. Here, using bioenergetics function assays on human GC cells, we reveal ligand-induced activation TLR2,...
For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker-based test, to preoperatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified.We conducted pilot study consisting 40 urine samples (20 each group), using label-free quantitative (LFQ) mass spectrometry,...
We report unexpected nongenomic functions of signal transducer and activator transcription (STAT) 5 species in the cytoplasm aimed at preserving structure function Golgi apparatus rough endoplasmic reticulum (ER) vascular cells. Immunoimaging green fluorescent protein-tagged-STAT5a protein localization studies showed constitutive association nonphosphorylated STAT5a, to a lesser extent STAT5b, with STAT5a centrosomes human pulmonary arterial endothelial smooth muscle Acute knockdown STAT5a/b...
Abstract The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in xenogeneic rat skin wound repair model, but mechanism remains unclear. In this study, we investigated effect on macrophage composite an abdominal subcutaneous model C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgamma null ) immunocompromised mice...
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...