A5016879803- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- RNA Research and Splicing
- Hemoglobin structure and function
- Glycosylation and Glycoproteins Research
- Heme Oxygenase-1 and Carbon Monoxide
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Protein purification and stability
- Neonatal Health and Biochemistry
- Allergic Rhinitis and Sensitization
- Immunotherapy and Immune Responses
- Down syndrome and intellectual disability research
- Proteoglycans and glycosaminoglycans research
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Genetics and Neurodevelopmental Disorders
- Computational Drug Discovery Methods
- Pediatric health and respiratory diseases
- RNA and protein synthesis mechanisms
- Respiratory Support and Mechanisms
- T-cell and B-cell Immunology
Parks Victoria
2017-2025
CSL (Australia)
2014-2024
CSL (United Kingdom)
2015-2019
Monash University
1997-2014
Monash Institute of Medical Research
1997-2014
The University of Melbourne
2014
Monash Medical Centre
1997-2004
Australian Regenerative Medicine Institute
2002
The Royal Melbourne Hospital
1993-1998
Walter and Eliza Hall Institute of Medical Research
1993-1998
Abstract Background and Objective Asthma‐COPD overlap (ACO) is characterized by patients exhibiting features of both asthma COPD. Currently, there no specific treatment for ACO. This study aimed to investigate the therapeutic potential targeting CD131, a shared receptor subunit IL‐3, IL‐5 GM‐CSF, in ACO development preventing acute viral exacerbations. Methods A two‐hit mouse model was established house dust mite (HDM) allergen sensitization asthma, elastase emphysema. In separate model,...
Rationale: Hemolysis occurs not only in conditions such as sickle cell disease and malaria but also during transfusion of stored blood, extracorporeal circulation, sepsis. Cell-free Hb depletes nitric oxide (NO) the vasculature, causing vasoconstriction eventually cardiovascular complications. We hypothesize that Hb-binding proteins may preserve vascular NO signaling hemolysis.Objectives: Characterization an archetypical function by which scavenger could hemolysis.Methods: investigated...
A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, development has been confounded because of HCV's high degree antigenic variability and the preferential induction type-specific immune responses with limited potency against heterologous viral strains genotypes. We showed previously deletion three variable regions from E2 receptor-binding domain (Δ123) increases ability human broadly neutralizing antibodies...
Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity contributes to several immunopathologies. Here, we report the crystal structure of IL-3 receptor α chain (IL3Rα) in complex with anti-leukemia antibody CSL362 reveals N-terminal domain (NTD), a also present granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, IL-13 receptors, adopting unique "open" classical "closed" conformations. Although extensive mutational analyses NTD epitope show...
Abstract Acute respiratory distress syndrome (ARDS) is triggered by various aetiological factors such as trauma, sepsis and viruses including SARS-CoV-2 influenza A virus. Immune profiling of severe COVID-19 patients has identified a complex pattern cytokines granulocyte macrophage-colony stimulating factor (GM-CSF) interleukin (IL)-5, which are significant mediators viral-induced hyperinflammation. This strong response prompted the development therapies that block GM-CSF other individually...
The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α shared common (βc, CD131) receptor. Evidence from animal models recent clinical trials demonstrate that these are critical mediators the pathogenesis inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids,...
Blocking the action of inhibitory molecules at sites central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism EphA4 receptor activity promotes recovery in mouse model lateral hemisection spinal cord injury. Here we assessed effect blocking activation using antagonist EphA4-Fc rat thoracic contusive Using ledged tapered balance beam open-field testing, observed...
The development of therapeutic vaccines for treatment established cancer has proven challenging. Cancer not only need to induce a robust tumor Ag-specific immune response but also overcome the tolerogenic and immunosuppressive microenvironments that exist within many solid cancers. ISCOMATRIX adjuvant (ISCOMATRIX) is able both cellular Ab responses protect mice against challenge, this insufficient result in regression tumors. In current study, we have used B16-OVA melanoma, Panc-OVA...
Background Chronic Obstructive Pulmonary Disease (COPD) is a heterogenous disease where chronic inflammation implicated in airway remodeling and emphysema. The CD131 receptor indispensable for signaling by the beta common (βc) family of cytokines encompassing GM-CSF, IL-5 IL-3, which instigate both Type-2 non-Type-2 inflammatory responses. This study aims to determine whether antagonising can prevent pulmonary inflammation, alveolar cell death emphysema development. Methods We performed...
This report describes the cloning of cDNAs encoding transmembrane and soluble isoforms a novel chain murine type I interferon (IFN) receptor characterization its capability to bind ligand transduce signals. The (murine IFNAR 2c) has an extracellular domain 215 amino acids intracellular 250 acids, with 48% acid 71% nucleotide identity human 2c. cDNA for (IFNAR 2a) encodes 221-amino polypeptide identical first 210 2c plus 11 acids. Northern blot analyses show that 2 is expressed as two...
Leukemia inhibitory factor (LIF) is a polyfunctional cytokine known to require at least two distinct receptor components (LIF alpha-chain and gp130) in order form high affinity, functional complex. In this report, we present evidence that there are truncated forms of gp130 normal human urine plasma: large with molecular weight approximately 100, 000, which similar previously described soluble serum, undescribed small 50,000. Using panel monoclonal antibodies raised against the extracellular...
Abstract Background Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, causal link between COPD/ACO remains to be established. Our study aimed model the natural history of COPD investigate cellular/molecular mechanisms that drive progression. Methods Allergic airways was established in three-week-old young C57BL/6 mice using...
Circulating levels of a soluble type I IFNR are elevated in diseases, such as chronic inflammation, infections, and cancer, but whether it functions an antagonist, agonist, or transporter is unknown. In this study, we elucidate the vivo importance IFNAR, (s)IFNAR2a, which generated by alternative splicing Ifnar2 gene. A transgenic mouse model was established to mimic 10-15-fold expression sIFNAR2a observed some human diseases. We lines, designated SolOX, transgene mRNA protein-expression...
The EphA4 receptor tyrosine kinase is a major regulator of axonal growth and astrocyte reactivity possible inflammatory mediator. Given that multiple sclerosis (MS) primarily an demyelinating disease in mouse models MS, such as experimental autoimmune encephalomyelitis (EAE), degeneration reactive gliosis are prominent clinical features, we hypothesised endogenous could play role modulating EAE. EAE was induced knockout wildtype mice using MOG peptide immunisation severity histological...
Preclinical studies have evaluated haptoglobin (Hp) polymers from pooled human plasma as a therapeutic protein to attenuate toxic effects of cell-free hemoglobin (Hb). Proof concept demonstrated efficacy Hp in hemolysis associated with transfusion and sickle cell anemia. However, phenotype-specific products might be desirable exploit phenotype specific activities 1-1 versus 2-2, offering opportunities for recombinant therapeutics. Prohaptoglobin (proHp) is the primary translation product...
Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that known to require at least two distinct receptor components (LIF α-chain and gp130) in order form high-affinity, functional, complex. Human LIF binds with unusually high affinity naturally occurring mouse soluble α-chain, this property was used purify stable complex of human from pregnant-mouse serum. Recombinant gp130 expressed, FLAG® epitope (DYKDDDDK) the N-terminus, methylotropic yeast Pichia pastoris purified using...