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.

PhD Positions

Click here for current PhD opportunities in Biological Sciences. But feel free to email me to discuss projects outside these areas and alternative sources of funding.


 

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