Research

Dermatology and Genetic Medicine

My research career was focused on the genes and proteins of the epidermis and in particular, genetic diseases that affect this outermost part of the skin. Consequently, I mainly worked at the interface between dermatology and genetic medicine.

Above: Fluorescence microscope image of a thin slice of human skin stained to reveal keratin K5 protein (red), filaggrin protein (green) and DNA (blue). K5 is involved in the inherited skin blistering disorder epidermolysis bullosa simplex (EBS). Filaggrin is important in atopic dermatitis (eczema), allergy and allergic asthma.

The black areas with blue spots at the bottom are parts of the dermis – the deeper part of the skin that bleeds if you cut it. The area including the red staining right up through to the green is the epidermis – the outermost part of the skin that doesn’t bleed but just weeps clear fluid when you graze it. The epidermis is extremely tough and is the barrier that protects your body from the outside world.

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Keratin disorders

(Panel a) Epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder caused by genetic mutations in either the keratin K5 or K14 genes, plus some other genes. I was involved discovering some of the genes that cause various forms of EBS, as well as progressing therapy development for this and related skin diseases.

(Panel b) Pachyonychia congenita (PC) is an inherited skin disease causing thickening and blistering of certain parts of the skin, particularly the palms and soles. I discovered the cause of this disorder and several other related conditions.

These diseases are painful, highly debilitating and remain incurable.

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Atopic dermatitis (eczema)

My career high, in 2005/6, was discovering the major gene (FLG; filaggrin) that is involved in predisposing people to develop eczema, allergy and asthma. My lab and our collaborators showed that an inherited deficiency of the filaggrin protein allows allergens and irritants into the skin, triggering these allergic conditions.

(Panel a) Atopic dermatitis (eczema) causes itchy inflammation of the skin, particularly in infants and young children. Many of these individuals go on to develop one or more allergies to various foods, dust mites, pet hair, pollen etc. Some develop an allergic form of asthma. Collectively, these conditions affect more than 20% of the human population.

 

Acknowledgements

I’d like to express my sincere gratitude to all the patients and their families around the world without whom my research would simply not have been possible.

Thanks also to my many mentors; my extensive network of clinical and scientific collaborators worldwide; the institutes in which I was privileged to work; and the funding agencies who generously supported my research.

Last but certainly not least, thanks to the many talented scientific, clinical and support staff who always had my back as we generated the enormous body of work summarised below. I wish them every success in their current and future science adventures, as well health and happiness outside the lab.

Short Biography

Irwin McLean BSc (Hons) PhD DSc FRS FRSE FMedSci MAE FRSB FRSA

Full name: William Henry Irwin McLean

Place of birth: Ballymoney, County Antrim, Northern Ireland

Current Honorary Positions

  • Emeritus Professor of Genetic Medicine, University of Dundee

  • Visiting Professor, Trinity College Dublin

  • Honorary Consultant Clinical Scientist, NHS Tayside

What my research group achieved over the years

  • Discovered dozens of faulty genes that cause a variety of inherited skin disorders

  • Developed genetic testing for a large number of hereditary skin diseases

  • Advanced understanding of the keratinocyte cells that make up the epidermis and other related tissues

  • Uncovered unknown functions of the structural proteins that give strength to the epidermis and related tissues (epithelia)

  • Identified the filaggrin gene as the major gene involved in atopic dermatitis (eczema), allergic asthma, and other allergies

  • Showed that defective skin barrier function is the key driver of eczema and allergy

  • Revealed that skin barrier function is an important target for eczema and allergy therapy

  • Developed a number of gene silencing therapy systems for genetic conditions

  • Designed and carried out drug discovery programmes aimed at inherited diseases

My academic qualifications

  • BSc (Hons) in Microbiology (1985), The Queen’s University of Belfast, Northern Ireland

  • PhD in Human Genetics (protein analysis in muscular dystrophy, 1988), The Queen’s University of Belfast, Northern Ireland

  • DSc in Human Genetics (molecular genetics of inherited skin disorders, 1999), The Queen’s University of Belfast, Northern Ireland

Elected Fellowships and Memberships

  • Fellow of The Royal Society of Edinburgh (FRSE); Elected 2004

  • Fellow of the Academy of Medical Sciences (FMedSci); Elected 2009

  • Fellow of The Royal Society (FRS); Elected 2014

  • Member of Academia Europea (MAE); Elected 2016

  • Fellow of the Royal Society of Biologists (FRSB); Elected 2020

  • Fellow of the Royal Society of Arts (FRSA); Elected 2020

Major Awards

  • Times Higher Education Supplement Research Project of the Year (2006)

  • CERIES Dermatology Research Prize (2006)

  • The Paul Gerson Unna Prize for Dermatology (2007)

  • The Royal Society Research Merit Award (2007)

  • American Skin Association Award (2009)

  • Buchanan Medal of The Royal Society (2015) for distinguished contributions to the medical sciences

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Buchanan Medal of the Royal Society (2015)

Awarded to Irwin McLean by the Royal Society “for his major contribution to our understanding of the genetic basis of heritable skin diseases.”

Royal Society profile page: click here.

Prize Lectures

  • René Touraine Lecture (European Society for Dermatological Research), Kyoto, 2008

  • Duhring Lecture (University of Pennsylvania), Philadelphia, 2009

  • Montagna Lecture (Society for Investigative Dermatology), Atlanta, 2010

  • Odland Lecture (University of Washington), Seattle, 2010

  • Tanioku Kihei Memorial Lecture (Japanese Society for Investigative Dermatology), Wakayama, 2010

  • The Rook Oration (British Association of Dermatologists) Birmingham, 2016

Publications and Metrics

  • 298 Peer-reviewed scientific journal articles

  • 9 Scientific book chapters

  • 11 Editorials

  • 6 Electronic publications

  • 10 Patents

  • >36,800 citations (as of July 2021)

  • h-Index = 100

  • i10-Index = 266

Most Highly Cited Research Papers

  • 3040 citations (July 2021):

    Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

    Palmer CNA, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJD, O’Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S and McLean WHI (2006)
    Nature Genetics 38: 441-446 (PubMed ID: 16550169)

  •  1147 citations (July 2021):

    Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris.

    Smith FJD, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, Liao H, EvansAT, Goudie DR, Lewis-Jones S, Arseculeratne G, Munro CS, Sergeant A, O'Regan G, Bale SJ, Compton JG, Digiovanna JJ, Presland RB, Fleckman P and McLean WHI (2006)
    Nature Genetics 38: 337-342 (PubMed ID: 16444271)

Research Grants

£26,873,841 to date, of which ~£1,700,000 is currently active (excludes almost £15m infrastructure grants)

Principal funding agencies: The Wellcome Trust, The Medical Research Council, DEBRA UK