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Profile: Ngee Han Lim

Profile: Ngee Han Lim

April 29, 2018


Funded by the Kennedy Trust

I was recruited in Nov 2014 as a career development fellow within the Arthritis Research UK centre of excellence for osteoarthritis pathogenesis at the Kennedy headed by Prof. Tonia Vincent. My association with both the Kennedy and the University of Oxford however, goes back further than this.

I was a biochemistry undergraduate at the University of Oxford from 1995 till 1999. From 1999 until the move of the Kennedy to Oxford in 2013, I was with the laboratory of Prof. Hideaki Nagase at the Kennedy in London, first as a research technician,
obtaining my PhD in 2008 and as a post-doc after. During this time, I have developed and utilized a vast array of techniques from different disciplines to answer questions regarding the roles of a clan of enzymes during arthritis.

This has included biochemical methods such as the assay development to quantify the activity of an enzyme family (the ADAMTSs) and protein engineering of an inhibitor to selectively inhibit the ADAMTSs to differentiate the roles of the ADAMTSs from another family (the MMPs) in tissues. I also worked with chemists within European Union consortia in the development of novel contrast agents and used them in preclinical imaging studies of arthritis models to follow the activities of two different MMPs in real time. This also allowed the selectivity and efficacies of drugs targeting those MMPs to be monitored.
I was recruited into the centre to specifically develop further contrast agents for osteoarthritis.

Osteoarthritis is diagnosed when a patient presents with joint pain and does not have other known joint diseases. There is currently no biomarker for patient stratification or for the evaluation of therapies. Clinical imaging is limited to X-rays that detect the very late reduction in joint space width due to the destruction of the cartilage within the joint. This is used to refer patients for joint replacement surgery. In the UK, 160,000 joint replacements are carried out annually and this is set to increase with the ageing population. An imaging biomarker would revolutionise the assessment of osteoarthritis and the evaluation of therapies.

Towards this end, the research group I am building is multidisciplinary, covering everything from the initial chemical
synthesis of the contrast agents through their testing in disease models and the subsequent computational analysis of the images obtained. We are currently a group of 3, consisting of a chemist, a biomedical engineer and myself.

Thus far, our major focus is on a technique we are calling DIPIC (Di-Iodotyrosinated Peptide Imaging of Cartilage), which uses an iodine containing peptide to image cartilage by the X-ray based CT (computed tomography) scan. A patent covering the technology has been filed through Oxford University Innovations and we are working to translate the method to the clinic. We are also developing ADAMTS-specific contrast agents to study ADAMTS
activity during osteoarthritis and to monitor the efficacy of ADAMTS inhibitors.