Biography

Ian Clark is a molecular cell biologist with a research focus on cartilage biology and osteoarthritis. A Biochemistry graduate, he undertook a PhD in the Rheumatology Research Unit in Addenbrooke’s Hospital, Cambridge developing assays to measure arthritis-relevant proteolytic enzymes. He won a Arthritis Research Campaign Copeman Fellowship to the USA where he began a project which led to the discovery of a cancer-associated SNP in the MMP1 gene. He returned to the Cambridge, UK on an Arthritis Research Campaign Postdoctoral Fellowship to develop his own interests in cartilage biology. In 2001, he spent a year on study leave working within the OA disease area in AstraZeneca Pharmaceuticals gaining an insight into drug development.

Since moving to UEA in 1996, he has published a number of key papers: (i) examining chondrocyte senescence in osteoarthritis; (ii) profiling the expression of firstly extracellular matrix-degrading proteinases, and latterly, all cellular proteases in normal vs. osteoarthritic human cartilage; (iii) defining the function of recently discovered metalloproteases in cartilage chondrocytes; (iv) demonstrating that histone deacetylase inhibitors are chondroprotective via their effects on metalloproteinase gene expression.

His current interests centre around (i) the impact of bioactive molecules derived from the diet on cartilage metabolism and osteoarthritis (ii) the role of microRNAs in chondrogenesis and osteoarthritis (iii) the role of proteases in Dupuytren’s disease.

Career History

2006 – date: Professor of Musculoskeletal Biology, School of Biological Sciences, University of East Anglia, Norwich, UK
2001 - 2006: Reader, School of Biological Sciences, University of East Anglia, Norwich, UK
2001: Team Leader, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, UK (sabbatical)
1996 - 2000: Arthritis Research Campaign Postdoctoral Research Fellow, School of Biological Sciences, University of East Anglia, Norwich, UK.
1994 - 1996: Arthritis Research Campaign Postdoctoral Research Fellow, Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
1993: Arthritis and Rheumatism Council Copeman Fellow. Taken up in the laboratory of Professor C.E. Brinckerhoff, Dept. of Biochemistry and Medicine, Dartmouth Medical School, New Hampshire USA.
1990 - 1992: Postdoctoral Fellow (funded by SmithKline Beecham Pharmaceuticals), Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
 


ResearcherID

http://www.researcherid.com/rid/D-1920-2009

All Publications

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Davidson, R. K., Jupp, O., De Ferrars, R., Kay, C. D., Culley, K. L., Norton, R., Driscoll, C., Vincent, T. L., Donell, S. T., Bao, Y., Clark, I. M.

(2013)

Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo : Sulforaphane is Protective in the Articular Joint

in Arthritis and rheumatism

65.

pp. 3130-3140

Full Text UEA Repository

(Article)


Culley, K. L., Hui, W., Barter, M. J., Davidson, R. K., Swingler, T. E., Destrument, A. P. M., Scott, J. L., Donell, S. T., Fenwick, S., Rowan, A. D., Young, D. A., Clark, I. M.

(2013)

Class I Histone Deacetylase Inhibition Modulates Metalloproteinase Expression and Blocks Cytokine-Induced Cartilage Degradation : Class I HDAC Inhibition is Chondroprotective

in Arthritis & Rheumatism

65.

pp. 1822-1830

Full Text UEA Repository

(Article)


Radwan, M., Gavriilidis, C., Robinson, J. H., Davidson, R., Clark, I. M., Rowan, A. D., Young, D. A.

(2013)

Matrix Metalloproteinase 13 Expression in Response to Double-Stranded RNA in Human Chondrocytes

in Arthritis & Rheumatism

65.

pp. 1290-1301

Full Text UEA Repository

(Article)


Soond, S. M., Smith, P. G., Wahl, L., Swingler, T. E., Clark, I. M., Hemmings, A. M., Chantry, A.

(2013)

Novel WWP2 ubiquitin ligase isoforms as potential prognostic markers and molecular targets in cancer

in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

1832.

pp. 2127-2135

Full Text UEA Repository

(Article)


Le, L. T. T., Swingler, T. E., Clark, I. M.

(2013)

Review: The Role of MicroRNAs in Osteoarthritis and Chondrogenesis : MicroRNAS in OA

in Arthritis & Rheumatism

65.

pp. 1963-1974

Full Text UEA Repository

(Article)


Davidson, R. K., Jupp, O., de Ferrars, R., Kay, C. D., Culley, K. L., Norton, R., Driscoll, C., Vincent, T. L., Donell, S. T., Bao, Y., Clark, I. M., Arthritis, Experimental, Cartilage, Articular

(2013)

Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo

in Arthritis and rheumatism

65.

pp. 3130-3140

Full Text UEA Repository

(Article)


Ollivere, B., Wimhurst, J., Clark, I., Donell, S.

(2012)

Current concepts in osteolysis

in Journal of Bone and Joint Surgery - British Volume

94-B.

pp. 10-15

Full Text UEA Repository

(Article)


Swingler, T., Wheeler, G., Carmont, V., Elliott, H., Barter, M., Abu-Elmagd, M., Donell, S., Boot-Handford, R., Hajihosseini, M., Munsterberg, A., Dalmay, T., Young, D., Clark, I.

(2012)

The expression and function of microRNAs in chondrogenesis and osteoarthritis

in Arthritis & Rheumatism

64.

pp. 1909-1919

Full Text UEA Repository

(Article)


Wilkinson, J., Davidson, R., Swingler, T., Jones, E., Corps, A., Johnston, P., Riley, G., Chojnowski, A., Clark, I.

(2012)

MMP-14 and MMP-2 are key metalloproteases in Dupuytren's disease fibroblast-mediated contraction

in BBA - Biochimica et Biophysica Acta

1822.

pp. 897-905

Full Text UEA Repository

(Article)


Wilkinson, J., Jones, E., Riley, G., Chojnowski, A., Clark, I.

(2012)

The Expression of Collagen-Degrading Proteases Involved in Dupuytren’s Disease Fibroblast-Mediated Contraction

In: Dupuytren’s Disease and Related Hyperproliferative Disorders.

pp. 143-149

Full Text UEA Repository

(Chapter)


Fields, J., Gardner-Mercer, J., Borgmann, K., Clark, I., Ghorpade, A.

(2011)

CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1

in Journal of Neurochemistry

118.

pp. 93-104

Full Text UEA Repository

(Article)


Norton, R., Sexton, D., Clark, I., Wilson, A., Hughes, D., O'Connell, M.

(2011)

Response of lung epithelial cells to inflammatory stimuli following exposure to the active form of vitamin D

in Proceedings of the Nutrition Society

70.

UEA Repository

(Article)


Norton, R., Sexton, D., Clark, I., Wilson, A., Hughes, D., O'Connell, M.

(2011)

IMMUNOMODULATORY EFFECTS OF 1, 25 (OH)(2) D-3 IN NORMAL AND TRANSFORMED HUMAN LUNG EPITHELIUM

In: ANTICANCER RESEARCH.

pp. 1499-1499

(Conference contribution)


Milner, J., Patel, A., Davidson, R., Swingler, T., Desilets, A., Young, D., Kelso, E., Donell, S., Cawston, T., Clark, I., Ferrell, W., Plevin, R., Lockhart, J., Leduc, R., Rowan, A.

(2010)

Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis

in Arthritis & Rheumatism

62.

pp. 1955-1966

Full Text UEA Repository

(Article)


Scott, J., Gabrielides, C., Davidson, R., Swingler, T., Clark, I., Wallis, G., Boot-Handford, R., Kirkwood, T., Talyor, R., Young, D.

(2010)

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

in Annals of the Rheumatic Diseases

69.

pp. 1502-1510

Full Text UEA Repository

(Article)


Pais, H., Nicolas, F., Soond, S., Swingler, T., Clark, I., Chantry, A., Moulton, V., Dalmay, T.

(2010)

Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

in RNA

16.

pp. 489-494

Full Text UEA Repository

(Article)


Barter, M., Pybus, L., Litherland, G., Rowan, A., Clark, I., Edwards, D., Cawston, T., Young, D.

(2010)

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

in Matrix Biology

29.

pp. 602-612

Full Text UEA Repository

(Article)


Clark, I., Rowan, A., Young, D., Clark, I. (ed.), Rowan, A. (ed.), Young, D. (ed.)

(2010)

Matrix metalloproteinase protocols 2nd Edition

Springer (Humana Press)

ISBN 978-1-60327-298-8

UEA Repository

(Book)


Rodgers, U., Clark, I.

(2010)

Expression of Recombinant MMP-28 in Mammalian Cells

In: Matrix Metalloproteinase Protocols.

pp. 55-65

Full Text UEA Repository

(Chapter)


Swingler, T., Kevorkian, L., Culley, K., Illman, S., Young, D., Parker, A., Lohi, J., Clark, I.

(2010)

MMP28gene expression is regulated by Sp1 transcription factor acetylation

in Biochemical Journal

427.

pp. 391-400

Full Text UEA Repository

(Article)


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Key Research Interests

Osteoarthritis
Osteoarthritis is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Approximately 8.5 million people in the UK have moderate to severe osteoarthritis and a recent survey shows that around 70% of them are in constant pain. Increasing age and obesity are both major risk factors for osteoarthritis and the health and economic burden of this disease will increase in the future. The Clark laboratory is investigating (i) the role of microRNAs in cartilage homeostasis and (ii) the impact of dietary bioactives on joint health.

(i) MicroRNAs (miRNAs) are small non-coding RNAs that have recently been recognised as important regulators of gene expression in human cells. A number of miRNAs are regulated across chondrocyte differentiation and their function is beginning to be delineated. Similarly miRNAs are differentially expressed in osteoarthritic cartilage compared to normal tissue. MicroRNA-140, highly and selectively expressed in cartilage, has been the focus of much work to date, though the full gamut of its actions is still to be defined. We are investigating miR-455 and miR-29, as well as a number of novel microRNAs that we have found in osteoarthritic chondrocytes.

(ii) A number of plant-derived phytochemicals have been proposed to have positive benefit on joint health and osteoarthritis though predominantly, these have not been studied in man to date. There are some published population-based study data to suggest that dietary constituents are associated with a reduction in the progression of OA in man. However, to date, dietary intervention trials have been small and of varying design, resulting in difficulty in interpreting the available data. We are investigating the role of sulforaphane, an isothiocyanate derived from eating broccoli and related vegetables, in osteoarthritis. So far, this compound has shown efficacy in three laboratory models of disease. We are currently undertaking a proof-of-principle human trial to ascertain if it will be similarly effective in man. We are also screening a number of diet-derived compounds for similar activity in chondrocytes with a view to investigating synergy between them.

Dupuytren’s disease
Dupuytren’s disease (DD) is a common disabling condition leading to contracture of the fingers, affecting over 2 million people in the UK. The only current treatment for established DD is surgery with high recurrence rates. Further surgery becomes more invasive with higher complication rates and incomplete contracture correction. There are no known drug treatments for the condition at present.

In the late 1980s and early 1990s, inhibitors of the matrix metalloproteinase family were developed for the treatment of cancers. Some of these compounds gave the side effect of a Dupuytren’s-like contracture. We have been trying to understand the role of metalloproteinases in Dupuytren’s disease. We measured the expression of two main families of metalloproteinases (the MMPs and the ADAMTSs) in tissue taken from Dupuytren’s patients at surgery. Furthermore, we were able to show a correlation between the levels of specific proteinases and recurrence of contracture post-surgery. We have gone on to show roles for specific proteases in models of cell-mediated contraction.
 

Teaching Interests

My teaching interests are around molecular biology and gene expression, cartilage biology, proteinases and osteoarthritis.

Professional Activities

  • Editorial Board of Arthritis Research & Therapy -1999 to date
  • Editorial Board of Current Rheumatology Reviews -2005 to date
  • Editorial Board of The Open Rheumatology Journal -2007 to date
  • Arthritis Research UK Research and Academic Capacity Committee - 2013 to date
  • Arthritis Research UK Research Fellowships Implementation Committee -2011 to date
  • Arthritis Research UK Scientific Adviser to USER Committee - 2011 to date
  • British Society for Rheumatology Heberden Committee - 2011 to date
  • British Society for Rheumatology Council - 2012 to date
  • External examiner - MRes in Musculoskeletal Ageing (MRC/ARUK CIMA) Institute of Ageing and Chronic Disease, University of Liverpool - 2013 to date

Administrative Posts

  • Course Director of Biological Sciences with a Year in Industry (C104)