A5045080298- Immune Response and Inflammation
- Trace Elements in Health
- Immune cells in cancer
- Drug Transport and Resistance Mechanisms
- Urinary Tract Infections Management
- NF-κB Signaling Pathways
- Immune responses and vaccinations
- Urinary Bladder and Prostate Research
- Cardiac electrophysiology and arrhythmias
- Glycosylation and Glycoproteins Research
- Heavy Metal Exposure and Toxicity
- CRISPR and Genetic Engineering
- Tuberculosis Research and Epidemiology
- Infectious Diseases and Tuberculosis
- Phagocytosis and Immune Regulation
- Pelvic floor disorders treatments
- Molecular Biology Techniques and Applications
- Pharmacological Effects of Medicinal Plants
- Genomics and Phylogenetic Studies
- Gut microbiota and health
- Genetic Mapping and Diversity in Plants and Animals
- Biochemical and Structural Characterization
- Peptidase Inhibition and Analysis
- Salmonella and Campylobacter epidemiology
- Prion Diseases and Protein Misfolding
The University of Queensland
2009-2022
University of Technology Sydney
2019-2021
National Institute of Diabetes and Digestive and Kidney Diseases
2019
National Institutes of Health
2019
Translational Research Institute
2014
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies the transcriptional responses primary human and mouse macrophages Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using custom platform permitting cross-species interrogation coupled with deep sequencing mRNA 5′ ends, we identified extensive divergence LPS-regulated orthologous...
The movement of key transition metal ions is recognized to be critical importance in the interaction between macrophages and intracellular pathogens. present study investigated role copper mouse macrophage responses Salmonella enterica sv. Typhimurium. chelator BCS (bathocuproinedisulfonic acid, disodium salt) increased survival S. Typhimurium within primary BMM (bone-marrow-derived macrophages) at 24 h post-infection, implying that contributed effective host defence against this pathogen....
We aimed to characterize antimicrobial zinc trafficking within macrophages and determine whether the professional intramacrophage pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) subverts this pathway. Using both Escherichia coli S. Typhimurium, we show that TLR signaling promotes accumulation of vesicular primary human macrophages. Vesicular is delivered E. promote microbial clearance, whereas evades response via pathogenicity island (SPI)-1. Even in absence SPI-1 exporter...
AIM:To develop a model of stress-induced senescence to study the hepatocyte associated secretory phenotype (SASP). METHODS:Hydrogen peroxide treatment was used induce in human HepG2 cell line.Senescence confirmed by cytochemical staining for panel markers including Ki67, p21, heterochromatin protein 1β, and senescence-associatedβ-galactosidase activity.Senescent hepatocytes were characterised gene expression arrays quantitative polymerase chain reaction (qPCR), conditioned media proteomic...
Urinary tract infections (UTI) are among the most common in humans. Uropathogenic Escherichia coli (UPEC) can invade and replicate within bladder epithelial cells, some UPEC strains also survive macrophages. To understand transcriptional programme associated with intramacrophage survival, we performed host-pathogen co-transcriptome analyses using RNA sequencing. Mouse bone marrow-derived macrophages (BMMs) were challenged over a 24 h time course two reference that possess contrasting...
The SET protein is a promising drug target in cancer therapy, because of its ability to inhibit the function tumor suppressor gene phosphatase 2A (PP2A). COG peptides, derived from apolipoprotein E (apoE), are potent antagonists SET; they induce cytotoxicity cells upon binding intracellular and modulate nuclear factor kappa B (NF-κB) signaling pathway. However, therapeutic potential peptides limited, their poor proteolytic stability low bioavailability. In this study, peptide, COG1410, was...
Abstract Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-κB, occurs in many cell types; however, additional mechanisms are required for specificity of responses innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective cytokine by direct...
Germline genes that are aberrantly expressed in nongermline cancer cells have the potential to be ideal targets for diagnosis and therapy due their restricted physiological expression, broad reactivation various types, immunogenic properties. Among such cancer/testis genes, components of PIWI-interacting small RNA (piRNA) pathway particular interest, as they control mobile genetic elements (transposons) germ thus hold great counteract genome instability cancer. Here, we systematically...
Abstract Protein glycosylation impacts the development and function of innate immune cells. The glycophenotypes glycan remodelling associated with maturation macrophages from monocytic precursor populations remain incompletely described. Herein, label-free porous graphitised carbon–liquid chromatography–tandem mass spectrometry (PGC-LC-MS/MS) was employed to profile high resolution N- O-glycome human monocyte-to-macrophage transition. Primary blood-derived CD14+ monocytes were differentiated...
The pseudokinase mixed lineage kinase domain-like (MLKL) is an essential effector of necroptotic cell death. Two distinct human MLKL isoforms have previously been reported, but their capacities to trigger death not compared directly. Herein, we examine these two isoforms, and further probe the features N-terminal domain that are required for Expression in HEK293T cells 201 amino acids (aa) sufficient cause death, whereas expression first 154 aa not. Given 1-125 able initiate necroptosis, our...
TLR-inducible zinc toxicity is an antimicrobial mechanism utilized by macrophages, however knowledge of molecular mechanisms mediating this response limited. Here, we show that E. coli exposed to stress within primary human macrophages reside in membrane-bound vesicular compartments. Since SLC30A exporters can deliver into the lumen vesicles, examined LPS-regulated mRNA expression Slc30a/SLC30A family members mouse and macrophages. A number these transporters were dynamically regulated both...
Detection of bacterial CpG‐containing DNA (CpG DNA) by innate immune cells is dependent on toll‐like receptor 9 (TLR9). Here we show that the expression tlr mRNA was induced in mouse bone marrow‐derived macrophages (BMMs) upon infection with facultative Gram‐negative intracellular bacterium Salmonella enterica serovar Typhimurium (S. typhimurium) . Treatment BMM inhibitory oligonucleotide (ODN) 2114, an antagonist TLR9 signalling, enhanced S. typhimurium numbers approximately fivefold,...
Toll-like receptor (TLR) signaling relies on Toll/interleukin-1 homology (TIR) domain-containing adaptor proteins that recruit downstream molecules to generate tailored immune responses. In addition, the palmitoylated transmembrane protein family member Scimp acts as a non-TIR-containing in macrophages, scaffolding Src kinase Lyn enable TLR phosphorylation and proinflammatory Here we report existence of smaller, naturally occurring translational variant (Scimp TV1), which is generated...
Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response therapy are urgently needed. This study examined the biomarker capacity of a panel plasma proteins alone, in conjunction with previously identified miRNA signature, TB disease.The expression nine (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF Eotaxin) was measured 100 control subjects patients, at diagnosis (treatment naïve) over course treatment (1-, 2- 6-month intervals). The...
Abstract A large Australian family affected with long QT syndrome (LQTS) was studied. The medical characteristics of the 16 clinically members were consistent LQT1. previously identified mutation in KCNQ1 found 12 individuals and 1 unaffected infant but absent 4 members. haplotype consisting specific alleles for microsatellites flanking associated mutation. This from four without mutation, who had three different haplotypes this region, indicating that LQTS is unlikely to be segregating...