Dr Deborah Mason - PhD
My research elucidates new signalling mechanisms that regulate bone and cartilage turnover, to provide therapeutic and diagnostic targets for osteoporosis, rheumatoid arthritis and osteoarthritis. This has led to the discovery of functional glutamatergic signalling in bone and synovium, and revealed new pathways that mediate cytokine- and mechanically- induced cartilage degradation. Modulation of glutamatergic signalling to enhance bone formation and inhibit pathological changes in arthritis, and delineating the role of PKR in arthritis, are current research priorities.
Glutamate Signalling: My work implicating the glutamate transporter GLAST-1 in mechanotransduction, and identifying glutamate as a potential anabolic target in bone is leading to new strategies for increasing bone formation. Our discovery that glutamate signalling mediates pathological responses in rheumatoid arthritis reveals a therapeutic opportunity whereby joint destruction could be prevented using already licensed glutamate receptor antagonists. Cloning and characterisation of the GLAST-1a splice variant is revealing new mechanisms of neurotoxicity.
Glutamate receptors function in Human Synoviocytes
PKR and ceramide in arthritis: Protein Kinase R(PKR) mediates stress and viral responses. We reported that PKR is activated in osteoarthritis and demonstrated that PKR mediates TNF a -induced degradation of cartilage. We have also shown that ceramide, a cytokine induced second messenger, influences cartilage matrix homeostasis via ERK signalling. These data reveal new mechanisms of cytokine mediated cartilage degradation that may be targeted in treatment or diagnosis of arthritis.
Biomechanics: Mechanical loading is a potent stimulus regulating both formation and degradation of bone and cartilage. Our studies on the effects of mechanical loading in bone and cartilage have implicated glutamatergic signalling, degradative enzymes, and the cytoskeleton in mechanotransduction.
- Smith and Nephew
- PJ Waters Bequest Fund
- Welsh Office of Research & Development
- The Wishbone Trust
- Henry Smiths Charitable Trust
Dr Phillippa Parsons (Smith and Nephew, York)
Dr Rheinault Parri ( Aston University)
Dr William Evans (Medical Physics, Cardiff and Vale NHS Trust)
Dr John Loughlin (Botnar Research centre, University of Oxford)
Prof Jane Worthington (ARC epidemiology Unit, Manchester)
Prof Ladiges and Dr John Morton (Dept Comparative Medicine, University of Washington)
Dr Jim Huggett (Centre for Infectious Diseases and International Health, University College London)
Dr Martin Taylor ( EMBL European Bioinformatics Institute, Cambridge, UK.)
School of Medicine : Dr Bronwen Evans (Child Health), Dr Anwen Williams (Rheumatology), Dr Jack Ham (Endocrinology) and Prof Anne Rosser (Clinical Neurosciences)
Welsh School of Pharmacy: Dr Steven Daniels
School of Biosciences: Prof Victor Duance, Dr Sophie Gilbert , Dr Cleo Bonnet and Dr Jim Ralphs