A5037488349- interferon and immune responses
- Respiratory viral infections research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Lysosomal Storage Disorders Research
- Viral gastroenteritis research and epidemiology
- Bacterial Infections and Vaccines
- Inflammasome and immune disorders
- Pediatric health and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- TGF-β signaling in diseases
- Viral Infections and Vectors
- Cytomegalovirus and herpesvirus research
- Mesenchymal stem cell research
- Respiratory and Cough-Related Research
- Extracellular vesicles in disease
- Cystic Fibrosis Research Advances
- Pregnancy-related medical research
- Influenza Virus Research Studies
- Carbohydrate Chemistry and Synthesis
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
Monash Medical Centre
2014-2024
Hudson Institute of Medical Research
2014-2024
Monash Health
2009-2024
Monash University
2011-2023
Australian Regenerative Medicine Institute
2023
Monash Institute of Medical Research
2013-2015
Women's and Children's Hospital
2007
Women's and Children's Health Network
2006-2007
The University of Adelaide
2005
Transforming growth factor-β (TGF-β) is one of the three related gene products TGF-β 1–3 that activate activin-like kinase receptor, ALK5, to elicit a bewildering array (patho)physiological effects. The label ‘master regulator’ well justified, as morphogen, inflammogen, immune- and inflammatory modulator, mediator tissue remodelling wound healing, fibrogen yet more functions are anticipated intense investigation this intriguing tightly regulated protein continues. Previous commentaries on...
Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute exacerbations, events often associated with virus infections. We examined the impact of GCS anti-viral defences replication assessed supplementary interferon (IFN) treatment. Here, we report that primary human cells vitro prior rhinovirus (RV) or influenza A (IAV) infection significantly reduces...
Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in variety of chronic respiratory diseases. The role this the pathogenesis lung inflammation not well defined. In study we examined effect NTHi on two important inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils 15 human-lung fibroblast epithelial cell lines 16 subjects. Cells stimulated with to measure reactive...
Human Rhinovirus (HRV) infection results in shut down of essential cellular processes, part through disruption nucleocytoplasmic transport by cleavage the nucleoporin proteins (Nups) that make up host cell nuclear pore. Although HRV genome encodes two proteases (2A and 3C) able to cleave such as Nup62, little is known regarding specific contribution each. Here we use transfected well HRV-infected cells establish for first time 3C protease most likely mediator Nup153 during infection, while...
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Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in mid-1940s. While their mode action on pathogens was originally attributed to DNA intercalating activity, work early 1970s suggested involvement host immune responses, characterized by induction interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations a mixture acriflavine instigate cyclic-GMP-AMP (cGAMP) synthase...
Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) suppress transcriptional induction antiviral and inflammatory genes protect animals from excessive damaging responses. We describe unexpected finding that minor DNA damage with CPT trigger a strong immune response through cyclic GMP-AMP synthase (cGAS) detection cytoplasmic DNA. This argues against having only...
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...
The innate immune response to virus must be balanced eliminate infection yet limit damaging inflammation. A critical arm of the antiviral is launched by retinoic acid-inducible-gene I (RIG-I) protein. RIG-I activated viral RNA then associates with mitochondrial signaling (MAVS) protein subsequently induce potent inflammatory cytokines. Here, we demonstrate E3 ubiquitin ligase 1 (MUL1) a crucial moderator signaling. MUL1 localized mitochondria where it interacts MAVS and catalyzes...
Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette causes protease imbalance with excess production proteases, which key process pathogenesis emphysema. The mechanisms responsible for this effect are not well-defined. studies demonstrate both vitro and vivo that significantly increases expression neutrophil macrophage extracellular traps coexpression elastase matrix...
Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of mucopolysaccharidoses. The disease caused by a deficiency lysosomal enzyme sulphamidase and results in storage glycosaminoglycan (GAG), heparan sulphate. MPS characterised widespread urinary excretion sulphate, progressive eventually profound neurological course. Gene therapy one few avenues treatment that hold promise sustainable for this disorder. murine gene cDNA was cloned into lentiviral vector high-titre virus produced....
Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis restricted to animal models, information about hMPV replication inflammatory immune responses human limited.Human primary bronchial epithelial cells (PBECs) from healthy asthmatic subjects those with COPD were infected hMPV, or without glucocorticosteroid (GCS) exposure. Viral replication, responses, apoptosis analyzed. We also...
Cytoplasmic detection of DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) is an essential component antiviral responses. Upon synthesis, cGAMP binds to the stimulator interferon (IFN) genes (STING) in infected and adjacent cells through intercellular transfer connexins forming gap-junctions, eliciting a strong IFN-β-driven response. We demonstrate here that Genistein, flavonoid compound naturally occurring soy-based foods, inhibits cGAS-STING signaling at two levels. First, Genistein...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme (ACE2) on host cells, via its spike protein, and transmembrane protease, serine (TMPRSS2) cleaves the spike-ACE2 complex facilitate virus entry. As rate-limiting steps for entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity COVID-19 severity. In silico modeling suggested natural bioactive flavonoid quercetin can bind a recent randomized clinical trial demonstrated that...
Injuries to the growth plate in children can result bone bridge formation, which ultimately lead limb length and angular deformities. The histological molecular changes associated with repair following Langenskiöld procedure, a surgical technique used remove impeding bridges, conjunction administration of recombinant human osteogenic protein-1 (rhOP-1) were examined using sheep model. Following treatment rhOP-1 there was an increase height immediately adjacent defect compared untreated...
<b>Introduction:</b> Novel dilators are required to overcome the reduced efficacy of β<sub>2</sub>-agonists in inflamed remodelled airways severe asthma. Relaxin (RLX), a Family Peptide Receptor 1 (RXFP1) agonist, reverses established allergen-induced fibrosis and <i>in viv</i>o AHR (Royce, Endocrinology, 2009) also elicits acute vitro</i> bronchodilation (Lam, Pharm & Ther, 2018). <b>Aim:</b> To assess if RLX potentiates relaxation salbutamol (SALB) inflamed, fibrotic mouse or human...