Matrix Biology and Tissue Repair

Our research aims to understand and manipulate the interface between extracellular matrix (ECM) and the diversity of cells in the craniofacial complex.

Goals

to elucidate and counteract pathological processes leading to tissue destruction in inflammation, cancer and ageing
to create functional tissue through application of life science principles.

Our research

It has become clear that the ECM and its interaction with various cells are critically important to regulate inflammation, repair/regenerative processes and invasive cancers.

Connective tissue cells control migration, survival and proliferation of endothelial and epithelial cells as well as recruitment and activation of antigen presenting cells that orchestrate the inflammatory response. Altered connective tissue cell responses are associated with many diseases, either because of direct involvement in the etiology or because of the fibrosis that accompanies the tissue damage.

Experimental models have been established within the group to decipher cellular interactions regulating distinct aspects of the repair and disease process. These relate to inflammation, angiogenesis, re-epithelialisation, cancer stromal cell interactions and ECM changes occurring with ageing.

The emphasis is to gain a molecular understanding of the role of post-translational modifications of proteins in organ system function, and how aberrant protein modifications or proteolysis contributes to pathogenesis.

Key areas

Osteoarthritis

The role of inflammation: metalloproteinases, transglutaminases, post-translational protein modification, biomarker development in association with the Arthritis Research UK Biomechanics and Bioengineering Centre.

Gluten sensitivity

Autoimmune response to transglutaminase: mechanism of extraintestinal disease manifestation, particularly CNS disease, development of new diagnostic modalities in association with the Sheffield Institute of Gluten-Related Diseases.

Cancer (prostate, breast and CNS) and inflammation

The role of metalloproteinases in cellular signalling, design of novel therapeutic approaches.

Impact

Gluten sensitivity-associated neurological dysfunction

Our research has directly contributed to the definition of a new disease entity (a gluten-mediated disorder presenting primarily as neurological dysfunction), linked it molecularly to an autoimmune process, developed a biomarker facilitating diagnosis and thereby enabling timely intervention and therefore prevention of debilitating damage to the central nervous system.

Spotlight on diagnostic assay Zedira 2015 - Transglutaminase antibodies in ataxia
Sheffield University press release - Centre for gluten-related diseases established
Cardiff/Sheffield University press release 2013 - Antibody links neurological disease to gluten sensitivity
Coeliac UK press release 2010 - Cardiff leading the way in coeliac disease research

A step-change in management of osteoarthritis

The Centre of Excellence established in Cardiff is a cross-School multidisciplinary network of researchers established to address the 'big' questions in the area of joint disease. N

ovel biochemical biomarkers for diagnosis and stratification of patients, as well as to assess prognosis and effect of therapy is the main focus of our research within this program. Detailed information can be found on the Arthritis Research UK Biomechanics and Bioengineering web site.

Arthritis Research UK Today magazine 2009 – Focus on Cardiff

Technology development

Selected publications

Wanger, T. M. et al. 2015. Differential regulation of TROP2 release by PKC isoforms through vesicles and ADAM17. Cellular Signalling 27 (7), pp.1325-1335. (10.1016/j.cellsig.2015.03.017)
Borko, L. et al., 2014. Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias. Acta Crystallographica Section D: Biological Crystallography 70 (11), pp.2897-2912. (10.1107/S1399004714020343)
Dewitt, S. , Francis, R. J. and Hallett, M. B. 2013. Ca2+ and calpain control membrane expansion during rapid cell spreading of neutrophils. Journal of Cell Science 126 (20), pp.4627-4635. (10.1242/jcs.124917)
Hadjivassiliou, M. et al., 2013. Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 80 (19), pp.1740- 1745. (10.1212/WNL.0b013e3182919070)
Thomas, H. et al., 2013. Transglutaminase 6: A protein associated with central nervous system development and motor function. Amino Acids 44 (1), pp.161-177. (10.1007/s00726-011-1091-z)
Carulli, S. et al., 2012. Cell surface proteoglycans syndecan-1 and -4 bind overlapping but distinct sites in laminin α3 LG45 protein domain.. The Journal of Biological Chemistry 287 (15), pp.12204-12216. (10.1074/jbc.M111.300061)
Hadjivassiliou, M. et al., 2010. Gluten sensitivity: from gut to brain. Lancet Neurology 9 (3), pp.318-330. (10.1016/S1474-4422(09)70290-X)

Our partners

Our research is aligned to major initiatives that aim to tackle the big questions in specific areas of biomedicine. This enables us to integrate our expertise in critical mass groupings to facilitate state-of-the-art discovery research to enhance the understanding of biological processes and to enable research translation for the benefit of patients:

Our funders

The following organizations have provided substantial support for our research programs and research infrastructure (last 5 years):

Age UK
Arthritis Research UK
Bardhan Research and Education Trust of Rotterdam
Cancer Research UK
Cancer Research Wales
Cardiff University President's Research Scholarships
Coeliac UK
EPSRC
Ryder Briggs
Sheffield Hospitals Charity
Tenovus

Our industry collaborators

We have joint programs with industry to enable research translation:

Zedira, Darmstadt, Germany

Our external academic collaborators

We have established a network of collaborations with key research groups in our research area nationally and internationally:

UK:
Dr Yvonne Alexander, University of Manchester
Professor Charles Archer, Swansea University
Dr Alison Gartland, University of Sheffield
Professor Marios Hadjivassiliou, Dr Nigel Hoggard, Professor David Sanders, & Professor Nicola Woodroofe, Royal Hallamshire Hospital/Sheffield Hallam University, Sheffield
Dr Joanna-Marie Howes & Professor Richard Farndale, University of Cambridge

International:
Dr Bela Anand-Apte, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, USA
Dr Anne Collins & Professor Norman J. Maitland, YCR Cancer Research Unit, University of York, UK
Professor Julio Bai, Carlos Bonorino Udaondo Gastroenterology Hospital Buenos Aires, Argentina
Dr Manuela Basso, University of Trento, Italy
Dr Sabrina Boscolo, Dr Tarcisio Not & Dr Enrico Tongiorgi, University of Trieste, Italy
Dr Vladena Bauerová-Hlinková, Professor Jozef Ševčík, Slovak Academy of Sciences, Bratislava, Slovakia
Dr Martin Hils & Dr Ralf Pasternack, Zedira, Darmstadt, Germany
Professor Kyotaka Hitomi, Nagoya University, Japan
Dr Alexandra Johnson & Dr John Lawson, Sydney Children's Hospital, Sydney, Australia
Professor Katri Kaukinen, Professor Markku Mäki & Professor Timo Reunala, University of Tampere, Finland
Professor Jeffrey Keillor, University of Ottawa, Canada
Dr Gunnar Kleinau & Dr Heike Biebermann, IEPE, Charité-Universitätsmedizin Berlin, Germany
Professor Mats Paulsson, Dr Miklos Sardy, & Dr Neil Smyth, University of Cologne, Germany
Professor Boris Pokusaev, Moscow State University of Environmental Engineering, Russia
Dr Patricia Rousselle, CNRS, IBCP Lyon, France
Professor Ludvig Sollid & Dr Jorunn Stamnaes, University of Oslo, Norway
Dr Reidun Stenberg, University of Örebro, Sweden
Professor Zsuzsa Szondy, University of Debrecen, Hungary