A5060611461- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Inflammatory Myopathies and Dermatomyositis
- Dermatological and Skeletal Disorders
- Cell death mechanisms and regulation
- DNA Repair Mechanisms
- Insect Resistance and Genetics
- Cancer-related gene regulation
University of South Australia
2014-2024
South Australia Pathology
2014-2024
Centre for Cancer Biology
2016-2024
The University of Adelaide
2011-2023
Jaffna Teaching Hospital
2017
Royal Adelaide Hospital
2014
Australian Research Council
2012
Abstract The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because the inability current therapies to kill stem cells (LSCs) with intrinsic resistance. Loss stress sensor growth arrest and DNA damage-inducible 45 alpha (GADD45A) is implicated in poor clinical outcomes, but its role LSCs AML pathogenesis unknown. Here, we define GADD45A as a key downstream target G protein-coupled receptor (LGR)4 pathway discover regulatory for loss promoting leukemia-initiating...
The pathogenic agent responsible for the expanded repeat diseases, a group of neurodegenerative diseases that includes Huntington's disease is not yet fully understood. Expanded polyglutamine (polyQ) thought to be toxic in certain cases, however, all genes can encode polyQ sequence. Since repeat-containing RNA intermediary common these hairpin-forming single-stranded has been investigated as potential agent. More recently, it become apparent most loci have transcription occurring from both...
Key Points Cyclin-dependent kinase 9 and bromodomain extraterminal inhibitors are synergistic in MLL-rearranged leukemia. Multiple AML driver genes downregulated by the combined therapy suggesting broad applicability for this subtype.
Abstract The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) show that rare variants affecting nuclear- mitochondrially-encoded complex I genes near-mutual exclusivity with isocitrate dehydrogenase 1 ( IDH1 ), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells or all display attenuated respiration, heightened sensitivity to...
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...
High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between RA. Our findings merit investigation inhibitors as therapeutics for IDH-mutated
Recent evidence supports a role for RNA as common pathogenic agent in both the ‘polyglutamine’ and ‘untranslated’ dominant expanded repeat disorders. One feature of all sequences currently associated with disease is their predicted ability to form hairpin secondary structure at level. In order investigate mechanisms by which hairpin-forming RNAs could induce neurodegeneration, we have looked alterations gene transcript levels hallmarks cellular response toxic RNAs. Three disease-associated...
Dominantly inherited expanded repeat neurodegenerative diseases are caused by the expansion of variable copy number tandem sequences in otherwise unrelated genes. Some repeats encode polyglutamine that is thought to be toxic; however, other do not indicating either multiple pathogenic pathways or an alternative common toxic agent. As these share numerous clinical features and RNA a intermediary, RNA-based pathogenesis has been proposed, based on its toxicity animal models. In Drosophila,...
Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington's disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 2. A shared genetic basis, overlapping clinical features for some these indicate that common pathways may contribute pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins RNA, have been identified the use model systems, account The such animal models enables identification distinct their 'molecular...
Previously, we hypothesized that an RNA-based pathogenic pathway has a causal role in the dominantly inherited unstable expanded repeat neurodegenerative diseases. In support of this hypothesis we, and others, have characterized rCAG.rCUG 100 double-strand RNA (dsRNA) as previously unidentified agent capable causing pathogenesis Drosophila model disease. Dicer, Toll, autophagy pathways distinct roles dsRNA pathology. Dicer dependence is accompanied by cleavage down to r(CAG) 7 21-mers. Among...
Inflammation is activated prior to symptoms in neurodegenerative diseases, providing a plausible pathogenic mechanism. Indeed, genetic and pharmacological ablation studies animal models of several diseases demonstrate that inflammation required for pathology. However, while there growing evidence inflammation-mediated pathology may be the common mechanism underlying including those due dominantly inherited expanded repeats, proximal causal agent unknown. Expanded CAG.CUG repeat...
The Sri Lankan Journal of Infectious Diseases (SLJID) is an open access, peer-reviewed, biannual journal published by the Society for Microbiology (SSM). considers articles from all professional disciplines involved in field infectious diseases. has been publication since 2011, included DOAJ 2018 and a member COPE 2021. SLJID practices double-blind peer review policy. From 2022, publishes accepted manuscripts online immediately after copy-editing, enabling rapid dissemination scientific...
<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>