Nexxus Scotland

Houslay, Miles

Gardiner Chair of Biochemistry, Institute of Biomedical and Life Sciences, University of Glasgow.

As the head of a highly talented and enthusiastic research team, Professor Miles Houslay enjoys a reputation as one of the most respected global authorities on the biological processes involved in inflammation at cellular level.

He came to Glasgow in 1984 intending to stay only a few years, but found the area to be so rich in research capability and scientific expertise that he has never left.

 Prior to coming to Glasgow, Prof Houslay carried out research on the behaviour of cells at the Universities of both Cambridge and Manchester.

His work was originally focused on the way lipids in cell membranes affect the functioning of the proteins embedded within them. Many of these proteins proved to be involved in signal transduction, which is where Prof Houslay's research efforts have subsequently developed.

When he relocated to Glasgow, funded by the Medical Research Council as well as various charities and industry bodies, Prof Houslay began looking at the signalling processes of cells with a view to switching off responses which can cause problematic inflammation in the body.

Prof Houslay is particularly interested in a signalling molecule known as cyclic AMP (cAMP), which is well known for mediating the action in heart and muscle of the ‘flight or fight' hormone, adrenaline.

His research group has been looking at novel ways to inhibit a family of enzymes called PDE4, which break down cAMP, to stop inappropriate inflammation in lungs and joints.

Prof Houslay says "In a number of major diseases, raising the level of cAMP in cells helps to fight off the molecules which cause inflammation. This can be achieved with new medicines being developed to treat asthma, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD) by inhibiting PDE4".

COPD is a disease common in smokers, whereby the tar and other toxins in cigarette smoke cause the lungs to become congested. This in turn affects  breathing.

At a cellular level, this is caused by the inflammatory response that can be stopped by raising the levels of cAMP in cells.

Prof Houslay explains "Smokers are putting so many toxins into their lungs that what is meant to be a defensive system effectively backfires. The cells helping to clear up the mess are so over-stimulated they become uncontrolled. That's why the lungs become clogged up."

A number of drugs are currently in Phase Three clinical trials which are aimed at inhibiting PDE4, thus switching off this reaction. These compounds target cells known as macrophages and T-cells involved in the immune response.

"If you raise cAMP in these cells it targets another enzyme called PKA," says Prof Houslay. "This switches off the receptors on the macrophages and T-cells which would otherwise trigger inflammation."

PDE4 inhibitors do two things: They cause the muscles in the lungs to relax which improves breathing, and they get rid of inflammation, which allows the lungs to heal and which again improves the patient's breathing.

The drugs currently in clinical trials take a few weeks to a month to take effect. However, Prof Houslay's team are looking at making inhibitors targeted at specific members of the family of about 20 PDE4 enzymes, and whether it may be possible to design inhibitors that are specific to a particular type of PDE4.

Prof Houslay has discovered that each of these 20 PDE4 enzymes has its own ‘postcode' which sends particular enzymes to the right part of the cell to regulate the immune response.  He says "We are designing molecules which block the postcode in the cell and  stop the individual PDE4 enzyme going to its normal place in the cell, therefore inhibiting the damaging part of the immune response.  This would create a much more effective drug which could revolutionise COPD therapy".

Prof Houslay is also working on a collaboration with Prof David Porteous at the University of Edinburgh and pharmaceutical giants Merck, based on the discovery of a link between a specific PDE4 called PDE4B1. A genetic link has been found between this enzyme and certain people with schizophrenia, which could feasibly lead to a therapy for the condition.

Prof Houslay insists the wealth of talent in the West of Scotland - as well as the availability of links to other academic and industry bodies - has been a pivotal part of his team's success.  He says "The science here really is terrific and I don't think it's any accident that a team in Glasgow has been responsible for one of the most ground-breaking developments in inflammatory disease for a long time. I have been able to attract a large research group throughout the years and we have created a lot of jobs.  The West of Scotland has been a great place to develop my research". 

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