A5028263566- interferon and immune responses
- MicroRNA in disease regulation
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Viral Infections and Vectors
- Cancer-related molecular mechanisms research
- RNA regulation and disease
- RNA Research and Splicing
- Circular RNAs in diseases
- Inflammasome and immune disorders
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Cytomegalovirus and herpesvirus research
- Liver Disease and Transplantation
- CRISPR and Genetic Engineering
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
- Macrophage Migration Inhibitory Factor
- Bacteriophages and microbial interactions
- Reproductive System and Pregnancy
- Cytokine Signaling Pathways and Interactions
Monash University
2016-2025
Hudson Institute of Medical Research
2016-2025
Renji Hospital
2022
Shanghai Jiao Tong University
2022
Hudson Institute
2022
Australian Regenerative Medicine Institute
2013-2020
Monash Institute of Medical Research
2007-2018
Monash Medical Centre
2011
Integrated DNA Technologies (United States)
2011
University College Dublin
2006-2008
Cytoplasmic accumulation of TDP-43 is a disease hallmark for many cases amyotrophic lateral sclerosis (ALS), associated with neuroinflammatory cytokine profile related to upregulation nuclear factor κB (NF-κB) and type I interferon (IFN) pathways. Here we show that this inflammation driven by the cytoplasmic DNA sensor cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) when invades mitochondria releases via permeability transition pore. Pharmacologic inhibition or genetic deletion cGAS...
Abstract Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease 1–7 , lupus-causing TLR7 gene variants is lacking. Here we describe lupus erythematosus caused by gain-of-function variant. sensor viral RNA 8 9 and binds to guanosine 10 – 12 . We identified de novo, previously undescribed missense Y264H variant in child with severe additional other patients lupus. The selectively increased sensing 2',3'-cGMP...
Although microRNAs (miRNAs) are key regulators of gene expression, little is known their overall persistence in the cell following processing. Characterization such to full appreciation regulatory roles. Accordingly, we measured miRNA decay rates mouse embryonic fibroblasts loss Dicer1 enzymatic activity. The results confirm inherent stability miRNAs, intracellular levels which were mostly affected by division. Using a panel six miRNAs representative global trend decay, establish...
Fine-tuning of inflammatory responses by microRNAs (miRNAs) is complex, as they can both enhance and repress expression pro-inflammatory mediators. In this study, we investigate following global miRNA depletion, to better define the overall contribution miRNAs inflammation. We demonstrate that positively regulate Toll-like receptor signaling using inducible Dicer1 deletion depletion. establish an important miR-19b in effect, which potentiates nuclear factor-κB (NF-κB) activity human mouse...
Abstract Human TLR7 and 8 (hTLR7/8) have been implicated in the sequence-dependent detection of RNA oligonucleotides immune cells. Although hTLR7 sequence-specific sensing short RNAs has inferred from studies murine TLR7, this yet to be established for hTLR7. We found that different ssRNA sequences selectively induced either TNF-α or IFN-α human PBMCs. The response ssRNAs observed PBMCs could replicated activated macrophage-like (THP-1) cells pretreated with IFN-γ. Surprisingly, suppression...
Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology.Here we report that survivin, protein implicated resistance, is overexpressed cancer stem cell pool doxorubicin-resistant breast cells.Moreover, by an active targeting system consisting RNA aptamer targeted against epithelial adhesion molecule Dicer substrate survivin siRNA, could deliver high dose siRNA cells xenograft tumours.Importantly,...
Abstract Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within compartments. Deficiency in subunit alpha causes COPA syndrome is associated with type IFN signalling, although upstream innate immune sensor involved was unknown. Using vitro models we find aberrant activation of STING pathway due deficient but probably not intra-Golgi transport. Further cytosolic DNA cGAS as essentially required drive signalling. Genetic...
MicroRNA-155 (miR-155) is highly expressed in many cancers such as B cell lymphomas and myeloid leukemia inflammatory disorders rheumatoid arthritis, atopic dermatitis, multiple sclerosis. The role of miR-155 both a promoter inflammation an oncogenic agent provides clear need for itself to be stringently regulated. We therefore investigated the transcriptional regulation response respective pro- anti-inflammatory mediators LPS IL-10. Bioinformatic analysis revealed Ets binding sites on...
Deep-sequencing reveals extensive variation in the sequence of endogenously expressed microRNAs (termed 'isomiRs') human cell lines and tissues, especially relation to 3′ end. From immunoprecipitation microRNA-binding protein Argonaute sequencing associated small RNAs, we observe 3′-isomiR variation, including for miR-222 where majority is extended by 1–5 nt compared canonical sequence. We demonstrate this heterogeneity has dramatic implications phenotype transfected cells, with longer...
Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients is an unsolved issue. Here, we systematically analyzed the aberrant expression patterns cervical using RNA-Seq data from The Cancer Genome Atlas (TCGA). We incorporated gene profiling, molecular signatures, functional pathway information with set enrichment protein-protein interaction (PPI) network analysis, to identify sub-networks genes. Those identified genes relating DNA replication...
There is a growing appreciation that the direct interaction between bacteriophages and mammalian host can facilitate diverse unexplored symbioses. Yet impact these may have on cellular immunological processes poorly understood. Here, we applied highly purified phage T4, free from bacterial by-products endotoxins to cells analyzed responses using luciferase reporter antibody microarray assays. Phage preparations were in vitro either A549 lung epithelial cells, MDCK-I kidney or primary mouse...
Short-interfering RNAs (siRNAs) have engendered much enthusiasm for their ability to silence the expression of specific genes. However, it is now well established that siRNAs, depending on sequence, can be variably sensed by innate immune system through recruitment toll-like receptors 7 and 8 (TLR7/8). Here, we aimed identify sequence-based modifications allowing design bifunctional siRNAs with both proinflammatory silencing activities, potentially increased therapeutic benefits. We found...
Human Toll-like receptors (TLRs) TLR7, TLR8, and TLR9 are important immune sensors of foreign nucleic acids encountered by phagocytes. Although there is growing evidence implicating TLR7 in the detection intracellular pathogenic bacteria, characterization such a role for TLR8 currently lacking. A recent genetic study has correlated presence single nucleotide polymorphism (SNP) (rs3764880:A>G; p.Met1Val) with development active tuberculosis, suggesting phagosomal bacteria. Here we provide...
Recent studies have established that mutations or deletions in microRNA (miRNA) processing enzymes resulting a global decrease of miRNA expression are frequent across cancers and can be associated with poorer prognosis. While very popular profiling studies, it remains unclear whether microarrays suited not to accurately detecting decreases seen cancers. In this work, we analyzed the profiles samples using Affymetrix following inducible genetic deletion Dicer1 . Surprisingly, up third...