A5019766243- Microtubule and mitosis dynamics
- Melanoma and MAPK Pathways
- Cardiac Ischemia and Reperfusion
- Traditional Chinese Medicine Analysis
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Neurogenesis and neuroplasticity mechanisms
- Cytokine Signaling Pathways and Interactions
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Cardiac Fibrosis and Remodeling
- Cell death mechanisms and regulation
- Genetic and Kidney Cyst Diseases
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- Neuroscience and Neuropharmacology Research
- Viral Infections and Immunology Research
- Computational Drug Discovery Methods
- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Renal and related cancers
- Muscle Physiology and Disorders
- Cardiac Valve Diseases and Treatments
- Amyotrophic Lateral Sclerosis Research
Royal Prince Alfred Hospital
2008-2024
The University of Queensland
2015-2024
UNSW Sydney
2024
The University of Melbourne
2010-2022
Northern Health
2022
National University of Singapore
1995-2020
Australian Psychological Society
2016
Biotechnology Institute
2012
Institute of Molecular and Cell Biology
1995-2009
Agency for Science, Technology and Research
2009
Stat3 is a member of the signal transducer and activator transcription family, which important in cytokine signaling. Gene ablation studies have revealed requirement for diverse biological processes (Akira, S. 2000. Oncogene. 19: 2607–2611; Levy, D.E., C.K. Lee. 2002. J. Clin. Invest. 109:1143–1148). Previously, function had been attributed exclusively to its transcriptional activity nucleus. In this study, we reveal an interaction between microtubule (MT)-destabilizing protein stathmin....
Mitochondria play essential roles in cellular energy production via the oxidative phosphorylation system (OXPHOS) consisting of five multiprotein complexes and also initiation apoptosis. NADH:ubiquinone oxidoreductase (complex I) is largest complex that catalyzes first step electron transfer OXPHOS system. GRIM-19 was originally identified as a nuclear protein with apoptotic nature interferon (IFN)- all-trans-retinoic acid (RA)-induced tumor cells. To reveal its biological role, we generated...
TDP-43 proteinopathies are characterized by loss of nuclear expression and formation C-terminal fragmentation accumulation in the cytoplasm. Recent studies have shown that can accumulate RNA stress granules (SGs) response to cell stresses this could be associated with subsequent ubiquinated protein aggregates. However, initial mechanisms controlling endogenous SGs during chronic disease not understood. In study we investigated mechanism processing SH-SY5Y neuronal-like cells exposed...
Stat3 is a member of the signal transducer and activator transcription family, which important for cytokine signaling as well number cellular processes including cell proliferation, anti-apoptosis immune responses. In recent years, evidence has emerged suggesting that also participates in invasion motility. However, how regulates these remains poorly understood. Here, we find loss expression mouse embryonic fibroblasts leads to an elevation Rac1 activity, promotes random mode migration by...
The impact of aberrant centrosomes and/or spindles on asymmetric cell division in embryonic development indicates the tight regulation bipolar spindle formation and positioning that is required for mitotic progression fate determination. WD40-repeat protein 62 (WDR62) was recently identified as a pole linked to neurodevelopmental defect microcephaly but its roles mitosis have not been defined. We report here utero electroporation neuroprogenitor cells with WDR62 siRNAs induced their cycle...
Background— Familial hypertrophic cardiomyopathy (FHC) is characterized by genetic and clinical heterogeneity. Five percent of FHC families have 2 FHC-causing mutations, which results in earlier disease onset, increased cardiac dysfunction, a higher incidence sudden death events. These observations suggest relationship between the number gene mutations phenotype severity FHC. Methods Results— We sought to develop, characterize, investigate pathogenic mechanisms double-mutant murine model...
Phosphorylation of STAT3 (signal transducer and activator transcription 3) is critical for its nuclear import transcriptional activity. Although a shorter STAT3β spliceform was initially described as negative regulator STAT3α, gene knockout studies have revealed that both forms play roles. We expressed STAT3α at comparable levels to facilitate direct comparison their functional effects, shown different cytokine-stimulated kinetics phosphorylation translocation. Notably, the sustained...
Abstract Malignant pleural mesothelioma (MPM) is often fatal, and studies have revealed that aberrant miRNAs contribute to MPM development aggressiveness. Here, a screen of identified reduced levels miR-223 in patient specimens. Interestingly, targets Stathmin (STMN1), microtubule regulator has been associated with MPM. However, whether regulates STMN1 the functions this disease are yet be determined. also regulated by c-Jun N-terminal kinase (JNK) signaling, but occurs plays role unknown....
Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause neuronal death in cerebral ischemic stroke. The overstimulated ionotropic exert their neurotoxic effects part by overactivation calpains, which induce catalyzing limited proteolysis specific cellular proteins. Here, we report that cultured cortical neurons and vivo rat model focal stroke, the tyrosine kinase Src cleaved calpains at site N-terminal unique domain. This generates truncated fragment ~52 kDa,...
WD40-Repeat protein 62 (WDR62) is a spindle pole required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly mutations lead to mitotic mislocalization highlighting critical requirement precise WDR62 spatiotemporal distribution although the regulatory mechanisms are unknown. Here we demonstrate that WD40-repeat region of microtubule association while disordered C-terminal regulates cell-cycle dependent compartmentation. In agreement with...
Amyotrophic Lateral Sclerosis (ALS) is characterized by degeneration of motor neurons in the brain and spinal cord. Cytoplasmic inclusions TDP-43 are frequently reported ALS patients. has also been shown to associate with stress granules (SGs), a complex proteins mRNAs formed response stimuli that temporarily sequester mRNA translation. The effect pathogenic mutations within glycine-rich regions (where majority ALS-causing occur) on SG dynamics poorly understood. To address this issue, we...
We have demonstrated that two hypertrophic agents, interleukin-1β (IL-1β) and leukemic inhibitory factor (LIF), altered cardiac myocyte morphology with striking similarity prompted us to investigate the common actions of these cytokines. compared phosphorylation/activation signal tranducer activator transcription 3 (STAT3), extracellular signal-regulated kinase (ERK), p38<sup>MAPK</sup>, c-Jun N-terminal mitogen-activated protein kinases (MAPKs). The phosphorylation STAT3 by IL-1β was...
Abstract WDR62 mutations that result in protein loss, truncation or single amino-acid substitutions are causative for human microcephaly, indicating critical roles cell expansion required brain development. missense retain expression represent partial loss-of-function mutants may therefore provide specific insights into radial glial processes growth. Here we utilized CRISPR/Cas9 approaches to generate three strains of mutant mice; V66M/V66M and WDR62R439H/R439H mice recapitulate conserved...
Objectives: The signal transduction pathways mediating the progression to failure have been intensively studied in a variety of vitro and vivo animal models. Recently, acute activation Janus kinases (JAKs) transducers activators transcription (STATs) has observed heart, but whether this is sustained ischemic heart disease (IHD) or dilated cardiomyopathy (DCM) not previously addressed. Methods: We assessed tyrosine phosphorylation STAT1, 3, 5 6 ventricular samples explanted human hearts with...
Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting stress, but how these processes regulated is not well defined. We recently demonstrated that PI3K(p110α) protects against myocardial infarction. The aim this study was to determine whether directly regulates components structure. To address question, unique three-dimensional virtual muscle model applied gene expression data from transgenic mice with increased or decreased...
The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to growth major brain lineages unknown. Here, we use Drosophila models dissect lineage-specific function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion significantly decreased neuroblast number, size was unchanged. In contrast, glial volume. Moreover, loss glia not only population also non-autonomously...
We have investigated heat shock stimulation of MAPK cascades in an interleukin 3-dependent cell line, BaF3. Following exposure to 42 °C, the stress-activated JNK MAPKs were phosphorylated and activated, but p38 remained unaffected. Surprisingly, also activated ERK a potent (>60-fold), delayed (>30 min), sustained (≥120 min) manner. These characteristics suggested novel mechanism activation became focus this study. A MEK-specific inhibitor, PD98059, inhibited by >75%. role for Ras response...