Professor Irwin McLean FRS FRSE FMedSci
Irwin McLean was Professor of Human Genetics at The University of Dundee until his retirement in March 2019. His research group had identified the causative genes for more than 30 human diseases, including a number of diseases of keratins and associated epithelial structural proteins. In particular, he had a long-standing interest in the genetics of skin fragility disorders such as epidermolysis bullosa simplex (EBS) and development of therapy for this and closely related keratin disorders, such as pachyonychia congenita (PC) and Meesmann epithelial corneal dystrophy (MECD). In recent years, the McLean group identified the filaggrin gene as the cause of the common dry skin condition ichthyosis vulgaris and also showed that these same mutations, carried by more than 10% of people across various populations, are the major genetic predisposing factor for atopic dermatitis and associated allergic conditions, including atopic asthma. This work demonstrated the importance of skin barrier function in preventing atopic eczema and paved the way for development of new therapeutic angles for this and related allergic diseases.
During 2011, Irwin established one of the first Discovery Partnerships with Academia (DPAc) with GlaxoSmithKline to develop small molecule drugs aimed at treating genetic disease. In 2014, he and colleagues established a £2m partnership with the Pfizer Rare Disease Consortium to further develop these compounds. In 2012, funded by a £5.9m Strategic Award from the Wellcome Trust, Irwin established the Centre for Dermatology and Genetic Medicine (DGEM) – a cross-College multidisciplinary research initiative aimed at translating basic science discoveries in the inherited skin diseases into new medicines. In 2015, Irwin’s laboratory relocated to the Division of Biological Chemistry and Drug Discovery within Life Sciences, due to his close interactions with the Drug Discovery Unit in developing therapy for skin disease.
In later years, Irwin’s focus shifted towards therapy development with multi-million-pound research programmes in RNA therapy and small molecule drug discovery aimed at inherited disorders of the epidermis and cornea, as well as atopic eczema and asthma. This work will now continue under the direction of Dr Robyn Hickerson.
Throughout his distinguished career, Irwin had over 300 publications submitted and accepted in some of the top leading scientific journals, collaborated with influential and key clinicians and scientists worldwide and was a respected editor, advisor and reviewer.
In recognition of his research work, Irwin won the Times Higher Education Research Project of the year 2006; The CERIES Dermatology Research Prize 2006; The Paul Gerson Unna Dermatology Research Prize 2007; Royal Society Research Merit Award 2007; and the American Skin Association Achievement Award 2009.
He was elected as a Fellow of the Royal Society of Edinburgh (2005), a Fellow of the Academy of Medical Sciences (2009) and a Fellow of the Royal Society (2014). He was given the top research prize lectures for the European (ESDR), North American (SID) and Asian (JSID) societies for dermatology research and was awarded the Royal Society’s 2015 Buchannan Medal for distinguished contributions to the medical sciences in general.
Smith FJD et al., Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nature Genetics 38:337-342 (2006).
Palmer CNA et al., Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics 38:441-446 (2006).
Sandilands A et al., Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nature Genetics 39:650-654 (2007).
Fallon PG et al., A homozygous frameshift mutation in the murine filaggrin gene facilitates enhanced percutaneous allergen priming. Nature Genetics 41:602-608 (2009).
Leachman SA et al., First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder. Molecular Therapy 8:442-446 (2010).
Irvine AD, McLean WHI, Leung DY (2011) Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 365: 1315-1327 (PubMed ID: 21991953)
Brown SJ et al., Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 127:661-667 (2011).
Zhao Y et al., Statins downregulate K6a promoter activity: a possible therapeutic avenue for pachyonychia congenita. J Invest Dermatol 131:1045-1052 (2011).
Pohler E et al., (2012) Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma. Nature Genetics 44: 1272-1276