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Professor Deborah Mason

Professor Deborah Mason

Professor, School of Biosciences; Director of Pre-Clinical Research

School of Biosciences

Email
masondj@cardiff.ac.uk
Telephone
+44 (0)29 2087 4561
Fax:
+44 (0)29 2087 4116
Campuses
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Users
Available for postgraduate supervision

Overview

I am Co Principal Investigator of the Arthritis Research UK Biomechanics and Bioengineering Centre in Cardiff University, where I lead the Preclinical Research Programme investigating the interaction between biomechanics and biology in joint tissues. I have established a platform of cell, animal and human models to investigate how mechanical load regulates joint pathology. My research elucidates new signalling mechanisms that regulate bone and cartilage turnover, to provide therapeutic and diagnostic targets for musculoskeletal diseases. This has led to the discovery of functional glutamatergic signalling in joint tissues, and revealed new pathways that mediate cytokine- and mechanically- induced cartilage degradation. My research focuses on translating glutamate receptor antagonists as a treatment for osteoarthritis, identifying mechanically-regulated biomarkers and developing a joint mimetic for drug screening.

I have led over 35 research projects (>£8M external funding, recently funded by Wellcome Trust, EPSRC, Versus Arthritis, NC3Rs, Life Sciences Bridging Fund, MRC Confidence in Concept, Arthritis Research UK), invented patents and collaborate with academics, NHS clinicians and industry. I am President of the British Orthopaedic Research Society and have recently served on the Orthopaedic Research Society Programme Committee and as a Topic Chair.

Roles

Cardiff

  • Module Leader BI3351 Contemporary Topics in Disease
  • Preclinical Research Director, Biomechnics and Bioengineering Research Centre Versus Arthritis

National

  • President, British Orthopaedic Research Society
  • Translational Theme Lead, Musculoskeletal Research Advisory Group, Versus Arthritis
  • Higher Level Evidence Theme Lead, OAtechplus

Interested in joining my lab as a self-funded post-graduate student or a postdoc/fellow? Please contact me by email.

Biography

Deborah Mason is a Professor in the School of Biosciences and is Co Principal Investigator and Preclinical Research Director in the Biomechanics and Bioengineering Research Centre Versus Arthritis at Cardiff University. Her research programme uses a range of cell, explant, animal and human models to determine how altered joint biomechanics influences biological signals. After her BSc in Zoology and Genetics and PhD in Evolutionary Genetics, her post-doctoral research implicated glutamatergic signalling in mechanically-induced bone formation. Since then, she has led >40 research projects encompassing biosciences, engineering and orthopaedics. Her research has identified new drug targets and biomarkers for osteoarthritis, and developed new in vitro models for drug screening and biomarker selection. This has led to granted patents and collaboration with pharmaceutical companies. Her overall ambition is to improve understanding of the biological mechanisms that link mechanical loading, pain, inflammation and joint destruction in arthritis, and exploit this knowledge for patient benefit. She is President of the British Orthopaedics Research Society and has served on Committees for the Orthopaedics Research Society, British Orthopaedic Research Society and Bone Research Society. She has organized and published outputs from international workshops on how to conduct clinical trials for post-traumatic osteoarthritis. She contributes extensively to teaching and public engagement activities.

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Publications

2021

2020

2019

2018

2016

2015

2014

2013

2012

2011

2010

2009

2008

2006

2004

2003

2002

2001

2000

1997

1996

1995

Teaching

I am an enthusiastic and effective lecturer contributing to a range of teaching activities (tutorials, lectures, workshops, practical, projects) across various levels and Degree Schemes (BSc: Biomolecular, Biomedical, Medical, Dental; MSc). I adapt my methods according to student feedback, peer assessment and student achievement. As Level 1 Co-ordinator for Biochemistry Degree Schemes, Molecular Biology Degree Scheme Co-ordinator and Final Year Tutor for all Biomolecular Schemes I have made major contributions to management, teaching, course design and administration. 

I currently Lead the final year Contemporary Topics in Disease Module, where cutting edge research in the School of Biosciences demonstrates how research can reveal pathological mechanisms and identify and test new treatments across a wide range of diseases.

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. As Preclinical Research Directorr in the Arthritis Research UK Biomechanics and Bioengineering Centre, I lead research investigating the links between pain, inflammation and pathology in human arthritis. We have developed a range of protocols and cell, explant, animal and human models to investigate how altered joint biomechanics influences biological signals.

Current research

  1. Lead Translation of glutamate receptors antagonists to veterinary osteoarthritis, RWIF Innovation for all, £9,880
  2. Applicant Mechano-transduction modelling of the bone niche driving prostate metastatic cancer. Cancer Research Wales (2019 -22) £147, 301
  3. Lead Could anti-inflammatory treatment at ACL reconstruction improve biological, functional and clinical outcomes? Knowledge, Economy Skills Scholarships 2 East Wales (2019-22) £80,385
  4. Lead We don’t care how much it hurts (we do care about your nociception), IUK (2019-20) £14,996.
  5. Lead Repurposing drugs to prevent posttraumatic osteoarthritis. Versus Arthritis (2019-20) £49,064
  6. Applicant. The role of size, shape and structure of bones and joints, in explaining common musculoskeletal diseases. Wellcome Trust Collaboration Award (2018-23) £1,711,356.00
  7. Applicant Glutamate receptor antagonists as a novel approach to treat cruciate ligament disease in dogs – an observational study, 2017-21, British Veterinary Orthopaedic Association, £4,582
  8. Co-lead Biomechanics and Bioengineering Research Centre. Versus Arthritis (2016-2022), £2M

I am a Professor in the School of Biosciences and Co Principal Investigator (PI) and Director of Preclinical Research at the Biomechanics and Bioengineering Centre Versus Arthritis, Cardiff University. I am a molecular and cell biologist in the field of musculoskeletal diseases. After my BSc in Zoology and Genetics and PhD in Evolutionary Genetics, my post-doctoral research revealed bone cell gene expression in vivo and implicated glutamatergic signaling in mechanically-induced bone formation. My research has revealed that glutamate release is regulated in arthritis, that glutamate transporters and receptors function in musculoskeletal tissues and that their inhibition protects against inflammatory and post-traumatic osteoarthritis in animal models. Investigating the role of glutamate in bone and joint disease has been the focus of my career and is leading to new therapeutic approaches for arthritis with industrial and clinical collaborators.

My research has expanded into investigating other mechanically-induced molecular signals in cell, animal and human models that we have created in our Centre. In 2009, we set up the first longitudinal study relating biomechanical effects of surgical realignment of knee joints by high tibial osteotomy in patients with osteoarthritis to biological signals. The 3D bone models we have created are being developed as potential drug screening tools and to reveal functional genomics underlying genome wide associations with osteoarthritis and bone mineral density.

My work encompasses biosciences, engineering and orthopaedics. My determination to bridge the translational gap between basic science discoveries and clinical medicine has extended my research to report expert opinions on trial design for post-traumatic osteoarthritis. To assess evidence and impact across disciplines I have conducted research to standardize reporting interdisciplinary research and molecular measurement.

My major contribution has been to reveal a role for glutamatergic signaling in musculoskeletal pathology. I have shown that glutamate transporters are mechanically regulated in bone cells and modulate bone formation, revealed a pathological role for glutamate receptors in arthritis, and linked this to new pathways of cytokine- and mechanically- induced bone and cartilage degradation. These signaling mechanisms provide new therapeutic/diagnostic opportunities for osteoporosis and arthritis leading to patents granted in US, Europe and China, and clinical and industrial partnerships. To progress this work, I have organised international expert groups and workshops to consider trial design for prevention of post-traumatic osteoarthritis and demonstrated efficacy of these drugs in preclinical models.

  1. Mason DJ, Suva LJ, Genever PG, Patton AJ, Steuckle S, Hillam RA, and Skerry TM (1997). Mechanically-regulated expression of a neural glutamate transporter in bone. A role for excitatory amino acids as osteotropic agents? Bone 20 (3):199-20.
  2. Flood S, Parri R, Williams A, Duance V and Mason DJ (2007) Modulation of interleukin-6 and matrix metalloproteinase 2 expression in human fibroblast-like synoviocytes by functional ionotropic glutamate receptors. Arthritis and Rheumatism 56(8): 2523-2534.
  3. Bonnet CS, Williams AS, Gilbert SJ, Harvey AK, Evans BA, and Mason DJ (2015). AMPA and kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis. Ann Rheum Dis 2015 Jan;74(1):242-51.
  4. Watt F, Corp N, Kingsbury S, Frobell R, Englund M, Felson D, Levesque M, Majumdar S, Wilson C, Beard D, Lohmander S, Kraus V, Roemer F, Expert Working Group Author Block and Conaghan P, Mason DJ (senior author) (2019) Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury. Osteoarthritis and Cartilage. 2019 Jan;27(1):23-33.
  5. Bonnet CS, Gilbert SJ, Blain EJ, Williams AS, Mason DJ (2020) AMPA and Kainate glutamate receptor antagonists prevent post-traumatic osteoarthritis. JCI Insight. 2020;5(13):e134055.

I have developed a series of cell, explant, and animal models and used them to investigate mechanically-induced signaling that drives osteoarthritis pathology. These include the first 3D osteocyte loading model and a mouse model of post-traumatic osteoarthritis for drug screening.

  1. Blain EJ, Gilbert SJ, Wardale RJ, Capper SJ, Mason DJ, Duance VC (2001) Up-regulation of matrix metalloproteinase expression and activation following cyclical compressive loading of articular cartilage in vitro. Arch Biochem Biophys 396:49-55.
  2. Blain EJ, Mason DJ, Duance VC (2002) The effect of cyclic compressive loading on gene expression in articular cartilage. Biorheology 40(1,2,3):111-117.
  3. Vazquez M, Evans BAJ, Riccardi D, Evans SL, Ralphs JR, Dillingham CM, Mason DJ (2014) A new method to investigate how mechanical loading of osteocytes controls osteoblasts Front. Endocrinol (Bone Research) Front. Endocrinol. doi: 10.3389/fendo.2014.00208
  4. Gilbert, S, Bonnet, C, Stadnik, P, Duance, V, Mason, DJ, and Blain, E. (2018) Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis. J Orth Res. 36, 8, 2118-2127 (Journal of Orthopaedic Research, Excellence in Basic Science Award 2019)

I have revealed new pathological mechanisms that govern cartilage responses to inflammatory signals involving the protein kinase R pathway.

  1. Gilbert SJ, Meakin L, Bonnet CS, Nowell M, Ladiges W, Morton J, Duance VC and Mason DJ (2014) Deletion of P58IPK, the Cellular Inhibitor of the Protein Kinases PKR and PERK, causes bone changes and Joint Degeneration in Mice Front. Endocrinol. (Bone Research) doi: 10.3389/fendo.2014.00174
  2. Gilbert SJ, Blain EJ, Vaughan-Thomas A, Duance VC and Mason DJ (2012) Protein kinase R plays a pivotal role in the oncostatin M and interleukin-1 signalling in bovine articular cartilage chondrocytes. European Cells and Materials 23: 41-57
  3. Gilbert SJ, Blain EJ, Duance VC and Mason DJ (2008) Sphingomyelinase decreases type II collagen expression in bovine articular chondrocytes via the ERK signaling pathway. Arthritis and Rheumatism 58:209-220.
  4. Gilbert SJ, Duance VC, Mason DJ (2004) Does PKR mediate TNF alpha and ceramide induced increases in expression and activation of MMPs in articular cartilage by a novel mechanism? Arthritis Res Ther 6:46-55.

I have also contributed to standards testing the strengths and limitations of molecular measurement by PCR.

  1. Sanders R, Bustin S, Huggett J and Mason DJ (2018) Improving the standardization of mRNA measurement by RT-qPCR. Biomolecular Detection and Quantification 15 (May): 13-17.
  2. Sanders R, Mason DJ, Foy CA, Huggett JF. (2014) Considerations for accurate gene expression measurement by reverse transcription quantitative PCR when analysing clinical samples. Anal Bioanal Chem. 2014 Oct;406(26):6471-83.
  3. Sanders R, Mason DJ, Foy CA and Huggett JF (2013) Evaluation of Digital PCR for Absolute RNA Quantification PLOS one 8(9): e75296.

Collaborators

COLLABORATIONS: Industrial Hospital Innovations, AvantiCell Sciences, LGC, Novartis, Boehringher-Ingelheim, Seda Pharmaceutical Services, Kirkstall, Biogelx. Academic Dr Genever (York), Prof Tobias (Bristol), Prof McGregor (Imperial), Prof Little (Sydney, Australia), Mr Wilson (Cardiff and Vale NHS Trust), Prof Fiona Watt (Oxford). Cardiff Prof Cathy Holt (Engineering), Prof James Birchall and Dr Charles Heard (Pharmacy).Prof Anwen Williams and Dr Bronwen Evans (Medicine), Dr Emma Blain,  Prof Val Sparkes (Healthcare).

Current research group members

Post Doctoral research associates

PhD students

  • Joel Alves
  • Ryan Jones

Supervision

I am interested in supervising students in the areas of:

  • developing new preventative treatments for osteoarthritis
  • early diagnosis of osteoarthritis
  • cell models for drug screening

Past projects

Current

  • Ryan Jones (2020-2023) Could anti-inflammatory treatment at ACL reconstruction improve biological, functional and clinical outcomes? Supervisors: Mason DJ and Holt CA
  • Joel Alves (2016-2023, part time PhD) Glutamate receptor antagonists as a novel approach to treat cranial cruciate ligament disease/rupture in dogs” Supervisors: Mason DJ
  • Alison Kinghorn (2018-2021) (part-time MD) Relating clinical, biological and biomechanical factors to improve patient outcomes after knee injury. Supervisors: Mason DJ and Holt CA

Awarded

  • Ben Egan (2016-2020) Developing and testing a novel percutaneous delivery system for the glutamate receptor antagonist NBQX to treat joint pain and disease.  Supervisors: Mason DJ, Charles Heard and James Birchall.
  • Nidal Khatib (2014-2017) Functional and biological assessment of a new implant material to treat focal cartilage defects. Supervisors: Holt CA and Mason DJ.
  • Rebecca Sanders (2010-2015) Development and evaluation of new standardisation methods for RNA measurement in connective tissue diseases. Supervisors: Mason DJ and Huggett JF (LGC)
  • Nicole Scully (2010-2014) Investigating the response to load of human osteocytes from different anatomical sites in health and disease, Supervisors: Evans BAE and Mason DJ
  • Marisol Vazquez (2009-2013) Development of a novel in vitro 3D osteocyte-osteoblast co-culture model to investigate mechanically-induced signaling Supervisors: Mason DJ, Evans BAE and Riccardi D
  • Karen Brakspear (2007-2010) Glutamate regulation for bone repair Supervisors: Mason DJ and Parsons PE (Smith and Nephew)
  • Sophie Flood (2001-2005) The role of glutamate in the inflammatory response of the knee Supervisors: Mason DJ and Duance VC
  • Emma Blain (1998-2002) The identification of mechanically regulated genes from articular cartilage that affects extracellular matrix turnover Supervisors: Duance VC and Mason DJ
  • Philippa Callender (1996-2000) Interactions of type IX collagen and their role in the development of osteoarthritis Supervisors: Duance VC and Mason DJ
  • Jim Francis Huggett (1997-2001) Characterisation of the Na+-dependent glutamate transporter (GLAST-1) in bone Supervisor: Mason DJ