School of Biosciences

Research

My research interests encompass the cellular and molecular events that are involved in maintaining articular cartilage tissue homeostasis, and the mechanism/s that propagate degeneration of the tissue as observed in the pathology of osteoarthritis. Osteoarthritis is a multi-factorial disease and one of the major risk factors is excessive mechanical load i.e. through sports injury, obesity. As an Academic Fellow within the Arthritis Research UK Biomechanics and Bioengineering Centre, and based in the School of Biosciences I manage the mechanical loading laboratory, where my research area is the identification of signalling pathways that mediate either anabolic or catabolic responses in connective tissues, in particular articular cartilage, intervertebral disc and meniscus. More specifically, my research interests are:-

• the role of the chondrocyte cytoskeleton (Figure 1), in particular the vimentin intermediate filaments, in sensing the application of a load on to the articular cartilage surface, and how these intracellular networks transduce these mechanical signals into a biochemical response.

Figure 1: The cytoskeleton of primary bovine chondrocytes depicting vimentin intermediate filaments,tubulin microtubules and F-actin microfilaments cultured in high density monolayer for 7 days, as visualised using scanning confocal microscopy.

• Understanding the mechanisms involved in cytoskeletal element dysregulation, as observed in osteoarthritic human cartilage and its relevance to tissue degeneration.
• Investigating the involvement of the cytoskeletal elements in intervertebral disc cell mechanotransduction.
• Delineating the role of the β-catenin canonical and non-canonical pathways in transducing mechanical signals in articular cartilage.
• Investigating why ankle osteoarthritis only develops as a result of previous mechanical trauma.
• Characterising the biochemical composition, biomechanical properties and mechanisms of mechanotransduction in the meniscus.

Collectively, the aims of my research and the projects that I am involved in are to (1) determine how important the cytoskeletal elements are in transducing mechanical signals that influence cartilage chondrocyte homeostasis and (2) understand the underlying mechanisms of cartilage destruction propagated by abnormal mechanical load.

Current Funding

Dr EJ Blain, Dr AY Ali & Professor VC Duance: Testing the efficacy of Boswellia frereana (Frankincence) as a nutraceutical for Osteoarthritis. MRC Development Pathway Funding Scheme (SARTRE), £29,834

Dr EJ Blain, Professor VC Duance: Involvement of the canonical and/or non-canonical Wnt signalling pathways in load induced cartilage degradation? Kuwait Embassy PhD studentship, £112,000

Dr EJ Blain: Investigating the interplay of mechanical load and Wnt3A on cartilage chondrocyte matrix homeostasis.Departmental Seedcorn, £4,400

Professor VC Duance & Dr EJ Blain: Understanding the role of vimentin in cartilage homeostasis and disease. Arthritis Research UK, £166,823

Previous Funding

Prof VC Duance, Dr EJ Blain & Dr RJ Wardale (Astra Zeneca): The role of the chondrocyte cytoskeleton in osteoarthritis. BBSRC Case PhD Studentship, £70,000 October 2005 – September 2008

Prof VC Duance & Dr EJ Blain: The role of the chondrocyte cytoskeleton in intervertebral disc degeneration. Dorothy Hodgkin PhD studentship, £70,000 October 2005 – September 2008

Prof VC Duance, Dr EJ Blain & Dr DJ Mason: Role of Thymosin b₄ in mechanotransduction in chondrocytes. Arthritis Research Campaign, £130,530 September 2003 – August 2006

Prof VC Duance, Dr EJ Blain & Prof AR Clarke: Is abnormal β-catenin signalling a key mediator of osteoarthritis? Arthritis Research Campaign, £73,140 April 2005 – October 2006

Prof V Duance & Dr E Blain: Can immotile chondrocytes be made to migrate and aid cartilage repair? Cardiff University Partnership Fund, £9,500 (pump-priming money)

Awards

2008 British Society for Matrix Biology Young Investigator Award

Affiliated Staff

Dr Yadan Zhang (Arthritis Research UK Research Associate)

Daisy Moore (MRC SARTRE technician)

Ayesha Al-Sabah (PhD student - Kuwait Embassy)

Previous PhD Students (co-supervisor)

2010 Rebecca Harrison

2009 Siyuan Li

Teaching Profile

MSc Tissue Engineering: Mechanotransduction (School of Biosciences)

EN3060 - Biomaterials and Tissue Engineering: (School of Engineering)

Laboratory supervision of Biomedical Sciences and Intercalated Medicine undergraduates, MRes in Biosciences and MSc Tissue Engineering students.

Collaborations

External

Dr Martin Knight, Dr Tina Chowdhury (School of Engineering, Queen Mary University of London).

Dr John Wardale (Addenbrookes Hospital, Cambridge).

Professor Drew Rowan (Institute of Cellular Medicine, Newcastle University).

Internal

Professor Vic Duance, Dr Sophie Gilbert, Professor Kevin Fox, Dr Neil Hardingham, Dr Ahmed Ali (School of Biosciences).

Professor Sam Evans (School of Engineering).

Mr Rhys Thomas, Mr Andy Metcalfe (Cardiff and Vale NHS Trust, University Hospital of Wales).

Committees

Committee member of the British Society for Matrix Biology

Membership of Societies

British Society for Matrix Biology

Biochemical Society

Cardiff Institute of Tissue Engineering and Repair

Funded by the Arthritis Research UK (website: http://www.arthritisresearchuk.org)