Irwin McLean is Professor of Human Genetics at The University of Dundee. His research group has identified the causative genes for more than 20 human diseases, including a number of diseases of keratins and associated epithelial structural proteins (e.g. Nature Genetics 9:273-278, 1995; Nature Genetics 11:450-452, 1995; Nature Genetics 13:450-457 1996; Nature Genetics 16:184-187 1997; New England J Med 351:2087-2100, 2004). In particular, he has 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 also 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 (Nature Genetics 38:337-34, 2006; Nature Genetics 38:441-446, 2006; Nature Genetics 39:650-654, 2007; Nature Genetics 41:602-608, 2009; New England J Med 365:1315-1327, 2011). 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. In recognition of this research, 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. Irwin was awarded the Royal Society’s Buchanan Medal for distinguished contributions to the medical sciences in 2015. He has given the top research prize lectures of the European (ESDR), North American (SID) and Asian (JSID) societies for dermatology research and he was awarded the Royal Society’s Buchannan Medal for distinguished contributions to the medical sciences in 2015.
In recent years the focus of Irwin’s work has shifted towards therapy development with multimillion pound research programmes in siRNA and small molecule therapy aimed at inherited disorders of the epidermis and cornea, as well as atopic eczema and asthma. This therapeutic translational research has already led to clinical trials. 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, College of Life Sciences, University of Dundee, due to his close interactions with the Drug Discovery Unit in developing therapy for skin disease. Also in 2015, he signed a collaboration with WaVe Life Sciences, Cambridge MA, to develop antisense therapy for inherited disorders. Irwin also has close links with the National Health Service and holds Honorary NHS Consultant Clinical Scientist positions in both Human Genetics and in Dermatology. He has been 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). Irwin works very closely with patient advocacy organisations DEBRA, PC Project and others to deliver patient support, molecular diagnosis and registries of genetically-defined subjects to enable clinical trials of new genetic medicines. Irwin is set to launch a new inherited skin disease patient advocacy organisation in 2016.
Major research themes:
• Biological functions and genetic diseases of keratinocyte structural proteins
• Small molecule drug discovery for genetic disorders
• Oligonucleotide therapy for inherited disorders
• Identification of genes causing inherited disorders of the epidermis and other epithelial tissues
• In vivo models of human disease