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Willingness to take Ph.D. students: Yes

Education/Academic qualification

Doctor of Medicine, University of London
Nitric oxide: its role in cutaneous health and disease

Biography

I am an academic dermatologist.  I studied medicine at St Thomas' Hospital, University of London. I then received my general medical training as an SHO in the north of England. After MRCP, I rouned this off with a year as a medical registrar in Cairns, Queensland. I returned to the UK for my dermatology training, initially at St John's Institute of Dermatology in London, followed by Registrar and Senior Registrar/Lecturer posts in Aberdeen and Edinburgh.  Having been bitten by the research bug under the mentorship of Ben Benjamin and Tony Ormerod in Aberdeen, I followed my clinical training with three years research training in Dusseldorf and Pittsburgh.  In 2002 I returned to Edinburgh, where I have been based since, as Senior Lecturer, and latterly Reader in dermatology.  

Current Research Interests

Nitric oxide and the skin

My most longstanding research interest has been on the role of NO in the skin and more recently the way in which this links the skin's response to ultraviolet (UV) radiation with systemic biology. Whilst still a trainee, I made the first description of NO production from the skin surface by sequential nitrate reduction (doi.org/10.1111/1523-1747.ep12363167), rather than by the NOS mediated cleavage from arginine for which Furchgott received his Nobel Prize. During my three years abroad, I expanded on this, trying to determine the function for skin generated NO, and whether this might reduce death of keratinocytes exposed to UV (doi.org/10.1152/ajpcell.00462.2002).  On my return to Edinburgh, working with my MD student Megan Mowbray, we showed that human skin contains huge stores of the NO precursor Nitrate (doi.org/10.1038/jid.2008.296).  With  my PhD student, Donald Liu, we were then able to demonstrate that these stores could be photoreduced to NO when skin is exposed to UV (such as sunlight), move to the systemic circulation, and thus lower BP (doi.org/10.1038/jid.2014.27).  This has been a hugely influential paper.  In addition to cardiovascular disease, a number of conditions appear to improve with increased sun exposure but not with vitamin D supplementation.  This UV-skin NO pathway may account for control of conditions as diverse as diabetes and metabolic syndrome (doi.org/10.2337/db13-1675), athletic performance (doi.org/10.1016/j.niox.2014.09.158), and pregnancy outcomes (doi.org/10.23889/ijpds.v1i1.262). This is leading to a re-consideration of public health advice on the risk-benefit ratio of sunlight exposure (doi:10.1001/jamadermatol.2017.4201). I am now running a clinical trial to find whether daily UVA phototherapy can be used as a treatment for high blood pressure.

 

Eczema

My second main research interest is in the aetiology of eczema. I have both a clinical and basic science interest in this and run a specialist eczema clinic together with my fellow consultant and former M Med Sci student, Dr Claire Leitch.  Eczema is very common, and appears to be due to defects in skin barrier function, as well as immune dysfunction.  Filaggrin gene expression is deficient in around half of eczema patients, with a resultant reduction in the filaggrin barrier protein. Working with a number of research fellows (including Claire), we were able to show that filaggrin also has an immunological role, as its breakdown product, urocanic acid reduces activation of antigen presenting cells in the skin (doi.org/10.1016/j.jaci.2015.11.040). UV is needed to create functional cis-urocanic acid, and also of course releases NO.  NO may also reduce skin inflammation by steering naïve T cells into the T regulatory cell lineage(doi.org/10.1016/j.jaci.2017.05.023). Barrier function is nonetheless important. The ‘antimicrobial peptide’ HBD2 is reduced in eczema and with the Donaldson group, we have been able to show that this has an additional function as an inhibitor of the ‘barrier busting’ proteases secreted by Staph aureus, which is carried almost universally by eczema patients(doi.org/10.1016/j.jid.2016.08.025).

Running a specialist eczema clinic allows me to undertake translational research studies such as those leading to the description by Dr Chengcan Yao and his group of a new PGE2-IL22 pathway(doi: 10.1126/science.aad9903) which may be involved in the development of allergic contact dermatitis (doi.org/10.1016/j.jaci.2017.04.045), and maybe a target for specific therapies.

Websites

https://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart

Qualifications

MB BS 1987

MRCP 1990

GMC Specialist Register (Dermatology) 1998

MD  2000

FRCP(Ed) 2006

Research activities & awards

  1. Scottish Dermatology Society

    Activity: Participating in or organising an eventParticipation in conference

  2. Tonight Programme

    Activity: OtherTypes of Public engagement and outreach - Media article or participation

  3. British Association of Dermatologists Annual Meeting

    Activity: Participating in or organising an eventParticipation in conference

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