A5032340430- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Chronic Myeloid Leukemia Treatments
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- Immune cells in cancer
- T-cell and B-cell Immunology
- Asthma and respiratory diseases
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Viral Infectious Diseases and Gene Expression in Insects
- Immunodeficiency and Autoimmune Disorders
- Receptor Mechanisms and Signaling
- Lymphoma Diagnosis and Treatment
- Bioactive Compounds and Antitumor Agents
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
South Australia Pathology
2014-2025
Centre for Cancer Biology
2013-2025
University of South Australia
2014-2025
Utrecht University
2011
Hanson Institute
1994-2008
The University of Melbourne
2003
Hôpital Saint-Louis
2002
St Vincents Institute of Medical Research
2000
Royal Adelaide Hospital
2000
Montreal Clinical Research Institute
1997
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic hemopoietic growth and activator of mature myeloid cell function. We have previously shown that residue 21 in the first helix GM-CSF plays critical role both biological activity high-affinity receptor binding. now generated analogues mutated at 21, expressed them Escherichia coli, examined for binding, agonistic, antagonistic activities. Binding experiments showed GM E21A, E21Q, E21F, E21H, E21R, E21K bound to...
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...
Pathological drug withdrawal syndrome is linked to accumulation of JAK2 phosphorylation in V617F myelofibrosis.
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...
Abstract The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems overexpressed in acute chronic myeloid leukaemia progenitor cells. It belongs to type I cytokine family which α-subunits consist of two fibronectin III-like domains bind cytokine, third, evolutionarily unrelated topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while NTD IL3Rα highly mobile presence IL-3,...
Protein kinase A (PKA) has long been recognized as playing a major role in many regulatory processes cells through its activation by the ubiquitous second messenger cAMP. We show here novel mode of PKA type II that is independent cAMP and is, instead, dependent on sphingosine. specifically activated sphingosine analog, dimethylsphingosine, but not sphingosine-1-phosphate or other lipids. Like cAMP, activates holoenzyme catalytic subunit alone, suggesting mediated subunits. However,...
The origin of pathogenic autoantibodies remains unknown. Idiopathic pulmonary alveolar proteinosis is caused by against granulocyte–macrophage colony-stimulating factor (GM-CSF). We generated 19 monoclonal GM-CSF from six patients with idiopathic proteinosis. used multiple V genes, excluding preferred V-gene use as an etiology, and targeted at least four nonoverlapping epitopes on GM-CSF, suggesting that driving the not a B-cell epitope pathogen cross-reacting GM-CSF. number somatic...
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,...
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However may evade the resist immune‐targeted treatment by promoting immune‐suppressive environment stimulating differentiation or recruitment immunosuppressive cells. Myeloid‐derived suppressor cells (MDSC) have been identified in range cancers often associated with tumour progression poor patient outcomes. Pancreatic cancer...
Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels a constant yet puzzling feature, as this lacks tyrosine kinase activity. Here, we show the heterodimeric IL3Rα/βc assembles into hexamers dodecamers through unique interface 3D...