Winnie L. Kan
A5064617920- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Chemokine receptors and signaling
- Asthma and respiratory diseases
- Immunotherapy and Immune Responses
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Eosinophilic Disorders and Syndromes
- HER2/EGFR in Cancer Research
- Immunodeficiency and Autoimmune Disorders
- Atherosclerosis and Cardiovascular Diseases
- Advanced Biosensing Techniques and Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bioactive Compounds and Antitumor Agents
- Phagocytosis and Immune Regulation
Centre for Cancer Biology
2014-2025
University of South Australia
2014-2025
South Australia Pathology
2014-2025
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 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,...
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...
After a 2-year hiatus due to the COVID-19 pandemic we welcomed back 10th Barossa meeting "Cell Signalling Cancer Medicine" during November 2023 in Valley, world class wine producing area with exceptional cellar doors and local gourmet food (Fig. 1A).The was co-hosted by Centre for Biology, South Australian Immunogenomics Institute Flinders University brought together first international national leaders ECRs share new information perspectives on fundamental discoveries overarching goal...
Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations the ubiquitin ligase Cbl occur frequently CMML share biological molecular features with clonal disease occurring children, juvenile (JMML). Here we analyzed clinical presentations, immunophenotype patients CBL mutations enrolled prospective Phase II trial stratified according to markers....
<p>Key interactions between distinct residues in the IL-3R ternary complex crystal structure.</p>
<p>Key interactions between distinct residues in the IL-3R ternary complex crystal structure.</p>
<p>IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.</p>
<p>The IL-3R dodecamer activates STAT1 to induce cell differentiation.</p>
<p>The IL-3R dodecamer activates STAT1 to induce cell differentiation.</p>
<p>Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.</p>
<p>Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.</p>
<p>Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.</p>
<p>Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.</p>
<p>Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in vivo engraftments.</p>
<p>IL3Rα/βc transcript and protein expression ratio in AML patient samples.</p>
<p>IL3Rα/βc transcript and protein expression ratio in AML patient samples.</p>
<p>Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in vivo engraftments.</p>