During his research career, his group identified the causative genes for several human diseases, including a number of disorders 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 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). Irwin has authored more than 330 articles, including many in the top ranked genetics and dermatology journals, with more than 37,000 citations. His publication h-factor is currently 100.
In 2005/6, 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 (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. He has given the top research prize lectures of the European (ESDR), North American (SID), Asian (JSID) and British (BSID) societies for dermatology research and was awarded the Royal Society’s 2015 Buchannan Medal for distinguished contributions to the medical sciences in general.
Latterly, Irwin’s work focused on therapeutics with multimillion pound research programmes in RNA therapy and small molecule drug discovery aimed at disorders of the epidermis and cornea, as well as atopic eczema and asthma. This translational research has 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 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, he signed a collaboration with WaVe Life Sciences, Cambridge MA, to develop antisense therapy for skin disorders.
Irwin has had close links with the National Health Service since the 1990s and maintains 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), a Fellow of the Royal Society (2014), a Member of the Academia Europaea (2016) and a Fellow of the Royal Society of Biologists (2020). During his career, Irwin has had close ties 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.
Professor McLean retired in 2019 because of ill health, however, his research group will remain active for the next few years, funded by a £2m MRC Programme Grant. Irwin is currently pursuing his many arts projects, particularly creative writing, and was elected as a Fellow of the Royal Society of Arts in 2020.
He continues to support his genetics and dermatology charities and is especially keen to support the RSE and other learned societies of which he is a Fellow. Irwin works part-time as a volunteer for a local community charity in the Scottish Highlands.