A5072309031- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Software Engineering Research
- Metabolism, Diabetes, and Cancer
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Diabetes and associated disorders
- Fungal and yeast genetics research
- Software Engineering Techniques and Practices
- S100 Proteins and Annexins
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Muscle Physiology and Disorders
- Advanced biosensing and bioanalysis techniques
- Adipose Tissue and Metabolism
- MicroRNA in disease regulation
- Cardiomyopathy and Myosin Studies
- Wnt/β-catenin signaling in development and cancer
- Cancer Genomics and Diagnostics
- Retinal Development and Disorders
- Immune Cell Function and Interaction
Children's Medical Research Institute
2020-2024
Garvan Institute of Medical Research
2013-2022
UNSW Sydney
2007-2022
St Vincent's Clinic
2011-2022
The University of Sydney
2020-2022
Broomfield Hospital
2022
St Vincent's Hospital
2006-2021
St Vincent's Hospital Sydney
2003-2021
St. Vincent's Birmingham
2011-2021
St. Vincent's Hospital
2021
Increased availability of fatty acids causes cell death and dysfunction in β-cell lines, isolated islets, animal models diabetes. From the MIN6 line, we selected two subpools that are resistant to palmitate-induced apoptosis. Protection was not universal because palmitate-resistant cells remained sensitive cytokine- streptozotocin-induced Palmitate oxidation incorporation into cholesterol ester (but triglycerides) were significantly higher than control cells. Consistent with these findings,...
The members of the class II phosphoinositide 3-kinase (PI3K) family can be activated by several stimuli, indicating that these enzymes regulate many intracellular processes. Nevertheless, to date, there has been no definitive identification their <i>in vivo</i> product, mechanism(s) activation, or precise roles. By metabolic labeling, we here identify phosphatidylinositol 3-phosphate as sole product insulin-dependent activation PI3K-C2α, confirming emerging role such a in signaling. We...
Abstract T follicular regulatory (Tfr) cells control the magnitude and specificity of germinal centre reaction, but how regulation is contained to ensure generation high-affinity antibody unknown. Here we show that this balance maintained by reciprocal influence interleukin (IL)-2 IL-21. The number IL-2-dependent FoxP3 + increased in peripheral blood human patients with loss-of-function mutations IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions phenotype cells, reducing expression...
Forces play diverse roles in vascular development, homeostasis and disease. VE-cadherin at endothelial cell-cell junctions links the contractile acto-myosin cytoskeletons of adjacent cells, serving as a tension-transducer. To explore tensile changes across live zebrafish, we tailored an optical biosensor approach, originally established vitro. We validate localization function tension sensor (TS) vivo. Changes observed using ratio-metric or lifetime FRET measurements reflect contractility...
Abstract Aims/hypothesis Pancreatic beta cell dedifferentiation, transdifferentiation into other islet cells and apoptosis have been implicated in failure type 2 diabetes, although the mechanisms are poorly defined. The endoplasmic reticulum stress response factor X-box binding protein 1 (XBP1) is a major regulator of unfolded response. XBP1 expression reduced islets people with but its role adult differentiated unclear. Here, we assessed effects Xbp1 deletion tested whether XBP1-mediated...
Abstract Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism Y1R, via non-brain penetrable antagonist BIBO3304, leads significant reduction in body weight gain due enhanced EE thereby reducing fat mass. Specifically thermogenesis brown adipose tissue (BAT) elevated UCP1 accompanied extensive browning white both mice humans....
The global incidence of thyroid cancer has been increasing rapidly, and this increase had an attendant burden on health systems. However, it is unclear how the disease differs among pre-2004 countries European Union (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden, UK), US, Australia, Canada, Norway (EU15+).
Advances in our understanding of the roles phosphatidylinositol phosphates controlling cellular functions such as endocytosis, exocytosis and actin cytoskeleton have included new insights into phosphatases that are responsible for interconversion these lipids. One is an entirely novel class phosphatase domain found a number well characterized proteins. Proteins containing this Sac include yeast Saccharomyces cerevisiae proteins Sac1p Fig4p. The also within mammalian phosphoinositide...
The yeast protein Sac1p is involved in a range of cellular functions, including inositol metabolism, actin cytoskeletal organization, endoplasmic reticulum ATP transport, phosphatidylinositol-phosphatidylcholine transfer function, and multiple-drug sensitivity. activity its relationship to these phenotypes are unresolved. We show here that the regulation lipid phosphoinositides <i>sac1</i> mutants defective, resulting altered levels all phos- phoinositides, particularly phosphatidylinositol...
Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor motility machinery would significantly modify its metastatic behavior. Protein kinase C alpha (PKC alpha) has been implicated in promotion of a migratory phenotype. We report that phorbol ester-induced polarization and directional breast carcinoma cells determined by 12-amino-acid motif (amino acids 313 to 325) within PKC V3 hinge domain. This also required direct association between...
Phospholipase D (PLD) has been strongly implicated in the regulation of Golgi trafficking as well endocytosis and exocytosis. Our aim was to investigate role PLD regulating biphasic exocytosis insulin from pancreatic beta-cells that is essential for mammalian glucose homeostasis. We observed activity MIN6 closely coupled secretion. Cellular increased response a variety secretagogues including nutrient cholinergic receptor agonist carbamoylcholine. Conversely, pharmacological or hormonal...
The insulin-stimulated trafficking of GLUT4 to the plasma membrane in muscle and fat tissue constitutes a central process blood glucose homeostasis. tethering, docking, fusion vesicles with (PM) represent most distal steps this pathway have been recently shown be key targets insulin action. However, it remains unclear how influences these processes promote insertion transporter into PM. In study we identified previously uncharacterized role for cortical actin GLUT4. Using high-frequency...
Actin has an ill‐defined role in the trafficking of GLUT4 glucose transporter vesicles to plasma membrane ( PM ). We have identified novel actin filaments defined by tropomyosin Tpm3.1 at uptake sites white adipose tissue WAT ) and skeletal muscle. In Tpm 3.1‐overexpressing mice, insulin‐stimulated was increased; while Tpm3.1‐null mice they were more sensitive impact high‐fat diet on uptake. Inhibition function 3T3‐L1 adipocytes abrogates translocation , amount filamentous is determined...
The protein kinase Akt mediates several metabolic and mitogenic effects of insulin, whereas activation C (PKC) isoforms has been implicated in the inhibition insulin action. We have previously shown that both PKC PKCepsilon are activated skeletal muscle insulin-resistant high fat-fed rats, to identify potential substrates for these kinases, we incubated recombinant with rat fractions vitro. specifically phosphorylated a 48-kDa was subsequently identified by mass spectrometry as Ndrg2. Ndrg2...