Dr Richard Weller
My research has two focuses: the effect of ultraviolet on systemic health; and on eczema.
- Fiona Cunningham - PhD student (co-supervised with Dr Chengcan Yao)
- Jenny Shelley - PhD student (co-supervised with Prof Donald Davidson)
Ultraviolet radiation from sunlight is the major environmental risk factor for skin cancer, and this has dominated dermatologists' view of sunlight for the century since this was confirmed. UV-induced skin cancer is, however, almost exclusively a disease of white skinned people. Work performed by my group and a small number of others internationally is identifying various health benefits of sun exposure. Vitamin D only accounts for a few of these health benefits, and identification of further mechanisms of UV-induced benefits is an important area of future research. The earliest people migrating to NW Europe after the last glacial maximum 8,500 years before the present day had brown skin. The transition to white skin occurred relatively rapidly as Neolithic agriculturalists replaced the original Mesolithic hunter-gatherers around 5,000 years before present. The reasons for this rapid change are unclear, but presumably are related to the need to maximise evolutionary fitness in a low light, high latitude environment.
Ultraviolet radiation and the skin
In 1996 I made the first description of nitric oxide (NO) production on the skin surface. NO at the time was known to dilate blood vessels and thus help regulate blood pressure - work for which the discoverers received the Nobel Prize for Medicine or Physiology in 1998 - but it was also involved in control of a number of other functions. Initially working in Aberdeen and Edinburgh and then at Heinrich-Heine University, Dusseldorf and the University of Pittsburgh I set out to uncover the role of this naturally produced NO in the skin. Following the standard dermatological dogma of the time I spent my time in Germany and America looking at the effects of NO on keratinocyte (skin cell) survival after sun exposure. Although I was able to show effects of NOS derived NO in inhibiting apoptosis in cell culture and murine models, I was unable to replicate this in man. Developing my work in Edinburgh on healthy volunteers, I was able to show that human skin contains large stores of nitrogen oxides (NOx) and that these are photo-reduced by UV radiation releasing NO to the circulation, with systemic effects, in particular lowering of BP. This work is summarised in a TED talk.
Work from my group and with a number of international collaborators is now finding a growing number of physiological and homeostatic processes that are dependent on this UV-skin NO mobilisation pathway. Partly spurred on by the discovery of this mechanism, the risk-benefit ratio for population sunlight exposure is being reconsidered in Europe, Australia and the USA. It is becoming clear that Vitamin D synthesis is not the only sun-dependent homeostatic mechanism, and may in fact only account for a small part of health benefits attributed to sun exposure. We have recently shown that UVA independently of vitamin D correlates inversely with deaths from COVID, which has important public health implications.
My main clinical research interest is in Eczema, and I also run the specialist adult eczema clinic for NHS Lothian in conjunction with Dr Claire Leitch. With Claire and others we have previously identified immunological functions of the filaggrin protein, which is usually deficient in eczema patients. I am currently co-supervising two PhD students looking at different aspects of eczema pathophysiology.
Current research activity
- My collaborator, Dr Chengcan Yao, has identified a new PGE2-IL22 pathway which we then showed to be involved in subtypes of eczema. PhD student, Fiona Cunningham, is working on this.
- Collaborator, Professor Donald Davidson, has identified an antiprotease function of human beta defensin which limits barrier function damage created by Staph aureus exotoxins. PhD student, Jenny Shelley, is continuing this work.
- I am principal investigator in Edinburgh for the EUROSTAD, DUPISTAD and A*STAR eczema studies.
I graduated in medicine at St Thomas' Hospital, University of London (now part of King's College, London) and undertook my general/internal medicine training in the north of England and in Australia. Having gained my MRCP, I trained in dermatology at the Institute of Dermatology (St John's) in London and in Aberdeen and Edinburgh. I spent some time out of my clinical training to complete a research MD degree. Having completed my dermatology training, I gained a scholarship from the University of Edinburgh, and spent three years in postdoctoral research training in the laboratories of Professor Victoria Kolb-Bachofen, Heinrich-Heine Universität, Dusseldorf, and of Dr Tim Billiar, University of Pittsburgh, USA. I was recruited from America to the post of Senior Lecturer and, latterly, Reader in Dermatology and Principal Investigator at the Centre for Inflammation Research, University of Edinburgh. My time is divided between clinical duties, where I am an honorary NHS Consultant Dermatologist with a particular interest in medical dermatology and eczema, and the University where I am active in research, and also a significant teaching commitment as Programme Director of the M.Med.Sci degree.
I have performed extensive media and public engament activities, most notably a TED talk on my UV research, which has now been viewed more than 1 million times.
I am programme director of the M Med Sci degree. I am dermatology lead for NHS Research Scotland.
British Skin Foundation
Chief Scientists Office