A5012036880- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- Developmental Biology and Gene Regulation
- Marine Sponges and Natural Products
- Particle physics theoretical and experimental studies
- Wnt/β-catenin signaling in development and cancer
- Chemical synthesis and alkaloids
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Microbial Natural Products and Biosynthesis
- Histone Deacetylase Inhibitors Research
- Neurogenesis and neuroplasticity mechanisms
- High-Energy Particle Collisions Research
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Quantum Chromodynamics and Particle Interactions
- Genomics, phytochemicals, and oxidative stress
- Neurological diseases and metabolism
Thomas Jefferson National Accelerator Facility
2000-2024
Griffith University
2014-2023
The University of Queensland
1989-2019
QIMR Berghofer Medical Research Institute
2019
Peter MacCallum Cancer Centre
2019
Westmead Institute for Medical Research
2019
University of Cambridge
2019
The University of Adelaide
1998-2015
Saskatchewan Research Council (Canada)
2014
The Kinghorn Cancer Centre
2013
The retromer is a trimeric cargo-recognition protein complex composed of Vps26, Vps29 and Vps35 associated with trafficking within endosomes. Recently, pathogenic point mutation the subunit (D620N) was linked to manifestation Parkinson's disease (PD). Here, we investigated details underlying molecular mechanism by which D620N in modulates function, including examination retromer's subcellular localization its capacity sort cargo. We show that expression PD-linked mutant redistributes...
SUMMARY There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities cells required molecular functional analyses. We describe here new model based on from human olfactory mucosa, organ smell, which regenerates throughout life neural stem cells. Olfactory mucosa biopsies were obtained healthy controls patients with either schizophrenia, neurodevelopmental psychiatric disorder, or Parkinson’s disease,...
Background Without appropriate cellular models the etiology of idiopathic Parkinson's disease remains unknown. We recently reported a novel patient-derived model generated from biopsies olfactory mucosa (termed neurosphere-derived (hONS) cells) which express functional and genetic differences in disease-specific manner. Transcriptomic analysis Patient Control hONS cells identified NRF2 transcription factor signalling pathway as most differentially expressed disease. Results tested robustness...
The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation and is mutated in several human cancers. We noted that a substantial percentage of colon cancers, protein undetectable despite the presence mRNA. To understand molecular mechanism regulation these we employed proteomics identified deubiquitinase (DUB) USP9X an interactor. antagonized ubiquitylation, Usp9x deletion caused Fbw7 destabilization. Mice lacking gut showed reduced secretory cell differentiation...
The protective role of nitric oxide in calcific aortic valve disease is mediated by S-nitrosylation proteins.
Background In the ubiquitin–proteasome pathway, ubiquitinated substrates either undergo degradation by proteasome or stabilization through action of deubiquitinating enzyme. We have previously found that enzyme Fam is colocalized with AF‐6, one effectors Ras small GTPase, at cell–cell contact sites in epithelial cells and interacts AF‐6 vivo vitro . has activity prevents ubiquitination intact cells. The β‐catenin, which accumulates as a cadherin/catenin complex, thought to be regulated...
Summary. When epidermal growth factor (EGF) was added to the medium for culture of preimplantation embryos, morphological development as determined by microscopic observation unaffected, but 333 nm-EGF stimulated total uptake [3H]leucine late morulae/blastocysts which had been cultured 24 h from morulae. Incorporation into protein these embryos increased 0·33, 3·3 and 33 nm-EGF, following a quadratic relationship producing less stimulation at nm, may indicate down regulation receptors. The...
Itch is a ubiquitin ligase that has been implicated in the regulation of number cellular processes. We previously have identified as binding partner for endocytic protein Endophilin and found it to be localized endosomes. Using affinity purification coupled mass spectrometry, we now ubiquitin-protease FAM/USP9X Itch. The association between was confirmed vitro by glutathione S-transferase pulldown vivo through coimmunoprecipation. FAM partially colocalize COS-7 cells at trans-Golgi network...
Abstract In the field of disease modeling, induced pluripotent stem cells (iPSCs) have become an appealing choice, especially for diseases that do not animal model. They can be generated from patients with known clinical features and compared healthy controls to identify biological bases disease. This study was undertaken determine variability in iPSC lines derived different individuals, aim determining criteria selecting models. We characterized 18 eight donors considered at three levels:...
The deubiquitylating enzyme Usp9x is highly expressed in the developing mouse brain, and increased expression enhances self-renewal of neural progenitors vitro. USP9X a candidate gene for human neurodevelopmental disorders, including lissencephaly, epilepsy X-linked intellectual disability. To determine if critical to mammalian brain development we conditionally deleted from progenitors, their subsequent progeny. Mating Usp9xloxP/loxP mice with expressing Cre recombinase Nestin promoter...
Abstract The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit downstream transcriptional co-activators YAP TAZ, which are implicated in various cancers. Recent studies have identified E3 ubiquitin ligases that negatively regulate via ubiquitination, yet few deubiquitinating enzymes (DUB) been implicated. In this study, we report DUB USP9X is an important regulator pathway. interacted strongly with kinase to a lesser extent WW45, KIBRA, Angiomotin, co-migrated...
Epilepsy is a common disabling disease with complex, multifactorial genetic and environmental etiology. The small fraction of epilepsies subject to Mendelian inheritance offers key insight into epilepsy mechanisms; pathologies brought on by mutations in single gene can point the way generalizable therapeutic strategies. Mutations PRICKLE genes cause seizures humans, zebrafish, mice, flies, suggesting seizure-suppression pathway evolutionarily conserved. This has never been targeted for novel...
Significance There is clear and irrefutable evidence that the Notch developmental signaling pathway an important driver in many cancers, specifically breast cancer. However, because of ubiquity this normal tissues, therapeutics targeting have been associated with significant deleterious side effects. Herein, we provide USP9x selectively drives cancer therapeutic inhibition prevents tumor progression without collateral damage to tissues.
A newly obtained sample of inclusive electron-nucleon scattering data has been analyzed for precision tests quark-hadron duality. The are in the nucleon resonance region, and span range 0. 3<Q2<5.0 (GeV/c)(2). Duality is observed both limited extended regions around prominent enhancements. Higher twist contributions to F2 structure function found be small on average, even low Q2 regime approximately 0.5 Using duality, an average scaling curve obtained. In all cases, duality appears a...
The Ras target AF-6 has been shown to serve as one of the peripheral components cell–cell adhesions, and is thought participate in adhesion regulation downstream Ras. We here purified an AF-6-interacting protein with a molecular mass ∼220 kD (p220) investigate function at adhesions. peptide sequences p220 were identical amino acid mouse Fam. Fam homologous deubiquitinating enzyme Drosophila, product fat facets gene. Recent genetic analyses indicate that activity plays critical role...
A method for the production of embryonic stem (ES) cell-embryo chimeras was developed that involves simple coculture eight-cell embryos on a lawn ES cells. After coculture, with cells attached are transferred to normal embryo culture medium and allowed develop blastocyst stage before reimplantation into foster mothers. Although initially attach outside embryos, they primarily colonize inner cell mass its derivatives. This results in efficient high levels chimerism including germ line. As...
Protein modification by one or more ubiquitin chains serves a critical signalling function across wide range of cellular processes. Specificity within this system is conferred E3 ligases, which target the substrates. Their activity balanced deubiquitylating enzymes (DUBs), remove from both substrates and ligases. The RING-CH ligases were initially identified as viral immunoevasins involved in downregulation immunoreceptors. orthologues, Membrane-Associated (MARCH) family represent subgroup...