1997-1998. ARC Post-doctoral Research Assistant, Wellcome Trust Centre for Matrix Research, University of Manchester.
1998-2003. ARC Senior Post-doctoral Research Assistant, School of Biological Sciences, University of East Anglia.
2003-2004. Dunhill Medical Trust Post-doctoral Research Assistant, School of Biological Sciences, University of East Anglia.
My research interests include the expression and regulation of metalloproteinases (MPs) and their inhibitors the TIMPs, particularly in the context of osteoarthritis (OA). My laboratory focus is how these genes are epigenetically regulated; by microRNAs, DNA methylation and chromatin modifications.
We have are also investigating the role of mitochondria and ubiquitination in OA.
Main techniques: Gene expression analysis/profiling (Real-time PCR, Taqman Low density arrays, microarray, RNA-seq). Cell signalling analysis. RNAi (siRNA, shRNA). miRNA analysis. Cas9/CRISPR. ChIP-seq. Transcription factor analysis (EMSA, mutagenesis, reporter assays). Epigenetic analysis. Models of osteoarthritis.
My laboratory will research the mechanisms by which HDACi block MP expression, determine the signalling pathways/mechanisms and identify the HDACs involved. We are specifically focussing on HDAC3.
Age is the major risk factor for Osteoarthritis. We are investigating the molecular mechanisms of how ageing impacts on cartilage.
Manipulating gene expression in cartilage is currently not possible therefore we have developed an interest in tissue engineering, to generate cartilage from the differentiation of stem cells. Using this model we have generated a series of -omics scale data to help understand what controls a chondrocyte phenotype.
We are developing CRISPR technology in the group both in terms of their ability to edit genes and also to regulate transcription. With collaborators we are using CRISPR to generate novel transgenics.
British Society for Matrix Biology (BSMB) Honorary Treasurer
Current funding is mainly from the Dunhill Medical Trust, the JGW Patterson Foundation, Arthritis Research UK, EU FP7 - Sybil, EU Horizon2020 - MSCA Global Fellowship (to Marta Radwan) and CIMA (MRC/Arthritis Research UK).
More than 7 million adults in the UK (15% of the population) have long-term health problems due to arthritis and related conditions. In 2001 incapacity benefit alone cost the nation £2.4 billion.
Metalloproteinases are the enzymes ultimately responsible for the collagen loss to cartilage seen in arthritic diseases. The design of small molecule inhibitors of the metalloproteinases remains a major focus of the pharmaceutical industry, yet has been largely unsuccessful, probably due to a lack of specificity of the compunds and side effects. Since arthritis is a debilitating, but not fatal disease, such side effects need to be minimised. We suggest that HDACi will be chondroprotective in all destructive arthritides, including both rheumatoid arthritis and osteoarthritis (other examples include: reactive arthritis, gout/pseudogout, psoriatic arthritis). They may also show utility in cartilage engineering/transplantation to protect cartilage explants or engineered/cultured cartilage from degradation. Many pharmaceutical companies are currently testing HDACi in cancer therapy trials, therefore these molecules potentially represent the next wave of drugs to fight the arthiitis.
I regularly supervise MRes/BMS students for laboratory projects and lecture on the MRes Biology or Ageing and Current trends in musculoskeletal disease modules..
I oversee MRes projects .