Nexxus Scotland

John Lockhart and Bill Ferrell

Professor John Lockhart
Professor of Physiology, University of the West of Scotland; Visiting Professor, University of Glasgow

Professor Bill Ferrell
Professor of Clinical Physiology, University of Glasgow; Visiting Professor, University of the West of Scotland 

Professors John Lockhart and Bill Ferrell can truly lay claim to being ground-breakers of research into both the mechanisms and potential treatments of chronic rheumatoid arthritis.

Prof Lockhart began his career in the late 1980s as an Honour student of Prof Ferrell, studying the role of neuropeptides in joint inflammation. His PhD in bioengineering centred on blood flow in diabetics, and how the aggregation of diabetic blood cells affected blood flow in microvessels.

Upon graduating with his PhD in 1988 from the University of Strathclyde, Prof Lockhart continued his work on blood flow at the University of Southern California in Los Angeles. He then worked in Heidelberg, Germany, until early 1990, looking at blood cell deformability in premature children, before moving to the internationally-renowned Mayo Clinic in Minnesota, to study the impact of nitric oxide on the regulation of the kidney microcirculation.

He met Prof Ferrell again while visiting Glasgow at a conference of the International Union of Physiological Sciences, and discussed his wish to return to Scotland. An opportunity existed in Prof Ferrell's laboratory, and the two have worked together extremely successfully ever since.

Prof Ferrell has long been a respected figure in this area; not least because of his pioneering work in developing the laser Doppler imager for the visualisation and measurement of joint blood flow.  A medical graduate of the University of Glasgow in 1973, Prof Ferrell harboured an early interest in the neurophysiology of joints, completing a PhD on the subject in 1977. His research interests turned to blood flow in inflamed joints as well as mechanisms of arthritis, and he returned to clinical work in addition to lecturing and research in 1997.

The combined expertise of Professors Lockhart and Ferrell is at the cutting edge of research in chronic rheumatoid arthritis and has yielded significant progress.

They jointly head up the Neurovascular Inflammation Group, a collaborative venture between the School of Engineering & Science at the University of the West of Scotland and the Centre for Rheumatic Diseases (CRD) at the University of Glasgow. The group's primary focus is on neurovascular regulatory mechanisms, and their disturbance during disease processes such as rheumatoid arthritis.  To this end they directly link with consultant rheumatologists at Glasgow Royal Infirmary including Professor Roger Sturrock, who heads the CRD, and Professor Iain McInnes. 

Lockhart and Ferrell had initially looked into the role of neuropeptides, prostaglandins and nitric oxide both in the regulation of synovial blood flow, and as pro-inflammatory mediators. More recently, however, they have discovered that a recently identified receptor type known as proteinase-activated receptor-2 - referred to as PAR-2 - could have a key role in the progression of rheumatoid arthritis. This work involved an international multi-institutional collaboration, including Professor Robin Plevin from the University of Strathclyde.

Prof Lockhart said "We were the first worldwide to demonstrate that PAR-2 was involved in chronic joint inflammation, and our group are currently funded by the Arthritis Research Campaign to investigate the therapeutic potential of inhibiting PAR-2 activation.  We've looked at the joints of patients with rheumatoid arthritis and found they have a high level of PAR-2 expression compared to patients suffering from osteoarthritis (non-inflammatory joint disease).  Consequently, inhibition of the receptor may present a novel anti-inflammatory therapy in the treatment of rheumatoid arthritis."  Further research is currently underway, and if this confirms that PAR-2 is significantly involved in the development of rheumatoid arthritis, the challenge will be to develop an antibody which will inhibit PAR-2.

Another promising area of research which they are currently looking at is the role of a receptor known as AT₁ receptor (ATR) in joint inflammation. Drugs to block this receptor were already well-used for treating cardiovascular diseases, but they have found that by administering a blocker to prevent angiotensin from binding to ATR,  joint swelling was reduced by up to 80 per cent.

This result, admitted Prof Ferrell, came as something of a surprise to both of them.  "If you had asked either of us about the significance of ATR in joint swelling, we would probably have suggested that it played only a minor role," he said. "Our experiments however show it has a very profound role in models of arthritis, and in cell cultures of tissue derived from patients with inflammatory arthritis.  The drug was already used for controlling blood pressure or treating heart failure, but it's now possible that it will also have beneficial potential in reducing inflammation in rheumatoid arthritis patients."

As double acts in the biosciences community go, there is no question that Lockhart and Ferrell are leading the way on the role of PAR-2 in arthritis; certainly in the West of Scotland if not the world.  With a level of experience and expertise unrivalled elsewhere - as shown by their work on the inflammatory effects of the PAR-2 and ATR- Prof Ferrell said it was natural the two scientists should work together in the West of Scotland.

He added: "Both of us recognise the value of the relationship which has achieved notable success.  I've remained in Glasgow throughout my career and I was really glad to have someone of John's experience and calibre rejoin me back in the lab."

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