Dr. Richard Weller MD, FRCP (Ed)
Rm 4112, Dermatology, First Floor, Lauriston Building
Lauriston Place
Edinburgh EH3 9YW
+44 (0)131 536 3229
email: r.weller@ed.ac.uk
Senior Lecturer, Dermatology
I was appointed to the post of Senior Lecturer in Dermatology at the University of Edinburgh in January of 2002. I also hold an honorary contract as a Consultant Dermatologist in NHS Lothian. I trained in medicine at St Thomas ’ Hospital in London , and then in general (internal) medicine in the north of England , and in Australia . I trained in dermatology at the St John’s Institute of Dermatology in London , then Aberdeen and Edinburgh . In the three years leading up to my current appointment I was a visiting research fellow at the Heinrich Heine University, Düsseldorf, Germany, and the University of Pittsburgh, USA.
Research Interests
I have two main research interests. My most longstanding [1-14] area of study has been in the role of Nitric Oxide (NO) in human skin physiology, both in healthy homeostasis and in disease. More recently I have become interested in the role of the skin barrier function deficiencies in the development of atopic disease.
Nitric oxide.
For the three years before my appointment in Edinburgh , I worked in laboratories of Professor Victoria Kolb- Bachofen, in Düsseldorf , Germany , and Dr Tim Billiar , Pittsburgh , USA . Papers from this time describe the anti-apoptotic role of NO in skin, released from irradiated keratinocytes, and in particular by eNOS [15;16] .
The actions of NO often do not follow simple dose-response curves, as do conventionally understood protein and peptide mediators, binding to a specific receptor. The mechanisms by which a small and ubiquitous molecule, NO, can produce spatially and temporally localised and specific effects is one of the keys to understanding the role of NO and a major underlying theme of much NO research. Experiments relying purely on cell culture frequently produce data which are either misleading, or frankly incorrect when extrapolated to man. Animal data are more helpful, but there are wide species variations in NO biology, as for example the much higher production of NO from iNOS in rodent macrophages than human.
My research is thus focused on in vivo studies in man. With my group, I have been investigating NO and NO derived effects on normal skin at rest and following UV irradiation. We have been studying whether autologously released NO limits UV induced apoptosis in human skin as my previous tissue culture and murine work would suggest. Initial experiments produced ambiguous results, and further work showed that this is due to the presence of significant stores of UV lysable, rapidly available tissue-bound NO [17;18] . These stores are in dynamic equilibrium with circulating nitrosospecies. We are now studying whether these stores may mediate the beneficial effects of sunlight on cardiovascular disease and hypertension.
During the course of our work on NO, we have developed a number of NO donors to use as experimental tools [18-20] , and also looked at the use of NO as an anti-infectious agent [12;21] and an enhancer of wound healing [22] .
Particularly significant members of my NO group have been:
Dr Megan Mowbray. (funded by the British Skin Foundation and Medical Research Scotland)
Dr Sharnika Abeyakirthi (Commonwealth Scholarship Commission)
Dr Xuejing Tan ( Dalian University , China )
Dr Beata Imko (Polish School of Medicine Memorial Scholarship)
Dr Amedea Seabra (British Skin Foundation and Campinas University , Brazil )
Key Collaborators:
Professor Adriano Rossi, Centre for Inflammatory Research, University of Edinburgh
Professor Russell Morris, Department of Chemistry, University of St Andrews .
Professor Martin Feelisch, Professor of Experimental Medicine, University of Warwick .
Drs Lieve Declercq and Mary Matsui, Estée Lauder Laboratories, Oeval , Belgium .
Dr Mike Finnen.
Skin Barrier Function.
My second main research interest is in the role of skin barrier function in the development of eczema and other atopic disease. The most exciting genetic finding in dermatology for many years has been the recent description by Professor Irwin Mclean that null mutations in the gene for the skin barrier protein filaggrin associate strongly with eczema (Weller, McLean.JRCP 2008 ). We are undertaking detailed phenotyping of a large cohort of eczema patients and measuring filaggrin genotype. Dr Roland Chu is studying the interaction between filaggrin and keratins of the cytoskeleton under the joint supervision of Dr Perdita Barran. Dr Siao Pei Tan is studying the effects of proteases and protease inhibitors on skin barrier function, jointly supervised by Dr Simon Brown in the Centre for Inflammation Research. Dr Ann Sergeant is studying barrier function and allergen penetration in eczema patients and Dr Sharizan Ghaffar is studying genotype-phenotype correlations in eczema patients.
Filaggrin group.
Dr Roland Chu (MRC Clinical training fellow)
Dr Ann Sergeant (RCPS Glasgow scholar)
Dr Sharizan Ghaffar (SpR)
Dr Siao Pei Tan(M.Med.Sci student)
Key Collaborators
Dr Perdita Barran ( University of Edinburgh , Department of Chemistry)
Dr Julia Dorin (MRC Human Genetics unit)
Facilities
In Edinburgh we have some of the best equipped dermatological clinical research laboratories in the UK , and use an array of modern techniques in our studies, such as skin microdialysis , iontophoresis , Doppler measurement of blood flow , chemiluminescent detection of NO, graded UV administration and TEWL. Our clinical investigation rooms are temperature and humidity controlled.
Teaching
I am lead author on the 4th edition of Clinical Dermatology (Weller, Hunter, Savin, Dahl), published by Blackwells in 2008.
I organise the undergraduate dermatology teaching, and chair the exam sub-board for the GP-Neuro-Senses module of the medical school.
Masters in Medical Science
I am programme director for the Masters in Medical Science degree. This is a one year research degree for medical graduates, designed to give them a solid groundwork in modern biomedical research. In comparison to science degrees, most undergraduate medical courses give little practical research exposure. The M Med Sci programme remedies this, giving the skills that a basic science degree would offer, but tailored to the needs of a potential clinical researcher. The degree comprises a 20% taught core, with the remainder of the time being spent carrying out a research project in an area relevant to the medical speciality of the student. Around 1/3 of students go on to a PhD from the Masters programme.
Reference List
1. Weller,R., Pattullo,S., Smith,L., Golden,M., Ormerod,A., and Benjamin,N. (1996) Nitric oxide is generated on the skin surface by reduction of sweat nitrate. J.Invest Dermatol., 107, 327-331.
2. Benjamin,N., Pattullo,S., Weller,R., Smith,L., and Ormerod,A. (1997) Wound licking and nitric oxide. Lancet, 349, 1776.
3. Ormerod,A.D., Dwyer,C.M., Weller,R., Cox,D.H., and Price,R. (1997) A comparison of subjective and objective measures of reduction of psoriasis with the use of ultrasound, reflectance colorimetry, computerized video image analysis, and nitric oxide production [see comments]. J.Am.Acad.Dermatol., 37, 51-57.
4. Weller,R. (1997) Nitric oxide--a newly discovered chemical transmitter in human skin. Br.J.Dermatol., 137, 665-672.
5. Weller,R., Dykhuizen,R., Leifert,C., and Ormerod,A. (1997) Nitric oxide release accounts for the reduced incidence of cutaneous infections in psoriasis [letter; comment]. J.Am.Acad.Dermatol., 36, 281-282.
6. Weller,R. and Ormerod,A. (1997) Increased expression of inducible nitric oxide (NO) synthase [letter; comment]. Br.J.Dermatol., 136, 136-137.
7. Jackson,M., Frame,F., Weller,R., and McKenzie,R.C. (1998) Expression of nitric oxide synthase III (eNOS) mRNA by human skin cells: melanocytes but not keratinocytes express eNOS mRNA. Arch.Dermatol.Res., 290, 350-352.
8. McKenzie,R.C. and Weller,R. (1998) Langerhans cells, keratinocytes, nitric oxide and psoriasis [letter; comment]. Immunol.Today, 19, 427-428.
9. Ormerod,A.D., Weller,R., Copeland,P., Benjamin,N., Ralston,S.H., Grabowksi,P., and Herriot,R. (1998) Detection of nitric oxide and nitric oxide synthases in psoriasis. Arch.Dermatol.Res., 290, 3-8.
10. Weller,R., Ormerod,A.D., Hobson,R.P., and Benjamin,N.J. (1998) A randomized trial of acidified nitrite cream in the treatment of tinea pedis. J.Am.Acad.Dermatol., 38, 559-563.
11. Weller,R. (1999) Nitric oxide, skin growth and differentiation: more questions than answers? Clin.Exp.Dermatol., 24, 388-391.
12. Weller,R., Price,R.J., Ormerod,A.D., Benjamin,N., and Leifert,C. (2001) Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J.Appl.Microbiol., 90, 648-652.
13. Sherratt,J.A., Weller,R., and Savill,N.J. (2002) Modelling blood flow regulation by nitric oxide in psoriatic plaques. Bull.Math.Biol., 64, 623-641.
14. Savill,N.J., Weller,R., and Sherratt,J.A. (2002) Mathematical modelling of nitric oxide regulation of rete peg formation in psoriasis. J Theor.Biol., 214, 1-16.
15. Weller,R., Billiar,T., and Vodovotz,Y. (2002) Pro- and anti-apoptotic effects of nitric oxide in irradiated keratinocytes: the role of superoxide. Skin Pharmacol.Appl Skin Physiol, 15, 348-352.
16. Weller,R., Schwentker,A., Billiar,T.R., and Vodovotz,Y. (2003) Autologous nitric oxide protects mouse and human keratinocytes from ultraviolet B radiation-induced apoptosis. Am.J.Physiol Cell Physiol, 284, C1140-C1148.
17. Mckay,D.A., Fitzpatrick,A., Turnbull,A., and Weller,R. (2004) Ultraviolet radiation and bradykinin induce erythema in man independently through a nitric oxide-dependent pathway. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 123, 432.
18. Mowbray,M., Tan,X., Wheatley,P.S., Morris,R.E., and Weller,R.B. (2008) Topically applied nitric oxide induces T-lymphocyte infiltration in human skin, but minimal inflammation. J Invest Dermatol, 128, 352-360.
19. Weller,R. (2003) Nitric oxide donors and the skin; useful therapeutic agents? Clin Sci.(Lond).
20. Seabra,A.B., Fitzpatrick,A., Paul,J., de Oliveira,M.G., and Weller,R. (2004) Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin. Br J Dermatol, 151, 977-983.
21. Finnen,M.J., Hennessy,A., McLean,S., Bisset,Y., Mitchell,R., Megson,I.L., and Weller,R. (2007) Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plate. Br J Dermatol, 157, 494-500.
22. Weller,R. and Finnen,M.J. (2006) The effects of topical treatment with acidified nitrite on wound healing in normal and diabetic mice. Nitric Oxide, 15, 395-399.
23. Mowbray,M., McLintock,S., Weerakoon,R., Lomatschinsky,N.,Jones,S.,
Rossi,A.G. and Weller,R. (2009) Enzyme-Independent NO Stores in Human Skin:
Quantification and Influence of UV Radiation