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.
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.
Key Research Interests
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 (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.
My teaching interests are around molecular biology and gene expression, cartilage biology, proteinases and osteoarthritis.
- 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
- Course Director of Biological Sciences with a Year in Industry (C104)