Irwin McLean | |
|---|---|
 | |
| Born | William Henry Irwin McLean 9 January 1963 [1] |
| Alma mater | Queen's University of Belfast (BSc, PhD, DSc) |
| Awards | |
| Scientific career | |
| Fields | |
| Institutions | University of Dundee |
| Thesis | Electrophoretic and immunological analysis of proteins in the muscular dystrophies (1988) |
| Website | lifesci |
(William Henry) Irwin McLean (born 1963) FRS [2] FRSE FMedSci [3] is Emeritus Professor of Genetic Medicine, at the School of Life Sciences, University of Dundee. [4] [5] [6] [7] [8] [9] [10]
McLean was educated at Queen's University of Belfast where he was awarded a Bachelor of Science degree with honours in microbiology in 1985 followed by a PhD in 1988 for electrophoretic and immunological analysis of proteins involved in muscular dystrophy. [11]
The McLean Lab investigates genetic disorders that affect the cells and tissues of the epithelium [12] [13] [14] [15] [16] [17] and is funded by the Medical Research Council (MRC) [18] and the Wellcome Trust. [19]
McLean was elected a fellow of the Royal Society in 2014. His nomination reads:
Irwin McLean is distinguished his major contributions to our understanding of the genetic basis of heritable skin diseases. Of particular note is his discovery that null mutations in filaggrin, which are carried by 10% of the population, not only cause the dry, flaky skin condition ichthyosis vulgaris but also strongly predispose individuals to the most common skin disorder, atopic eczema, and the associated phenotypes of atopic asthma, allergy and hay fever. This research has revolutionised the field by showing that a skin barrier defect, rather than an immunological defect, is the primary cause of eczema and focused attention on improving barrier function to treat these common diseases. He was also the first to map and identify the causative genes for a number of monogenic cell fragility disorders affecting the epidermis, its appendages and other epithelial tissues, including pachyonychia congenita, muscular dystrophy with epidermolysis bullosa simplex and Meesmann corneal dystrophy. His work has established that a primary function of the intermediate filament cytoskeleton, its attachment structures and modifying proteins is to provide epithelial tissues with mechanical strength. [2]
Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the difference between those terms is not standardized.
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
Ichthyosis vulgaris is a skin disorder causing dry, scaly skin. It is the most common form, and one of the mildest forms, of ichthyosis, affecting around 1 in 250 people. For this reason it is known as common ichthyosis. It is usually an autosomal dominant inherited disease, although a rare non-heritable version called acquired ichthyosis exists.
Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis under the trade name Elidel.
Keratin 2A also known as keratin 2E or keratin 2 is a protein that in humans is encoded by the KRT2A gene.
Atopy is the tendency to produce an exaggerated immunoglobulin E (IgE) immune response to otherwise harmless substances in the environment. Allergic diseases are clinical manifestations of such inappropriate, atopic responses.
Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which can thicken over time. AD may also simply be called eczema, a term that generally refers to a larger group of skin conditions.
Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during terminal differentiation of epidermal cells. In humans, profilaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21.
Desmoglein-1 is a protein that in humans is encoded by the DSG1 gene. Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis.
Milk allergy is an adverse immune reaction to one or more proteins in cow's milk. Symptoms may take hours to days to manifest, with symptoms including atopic dermatitis, inflammation of the esophagus, enteropathy involving the small intestine and proctocolitis involving the rectum and colon. However, rapid anaphylaxis is possible, a potentially life-threatening condition that requires treatment with epinephrine, among other measures.
Urocanic acid is an intermediate in the catabolism of L-histidine.
Tonofibrils are cytoplasmic protein structures in epithelial tissues that converge at desmosomes and hemidesmosomes. They consist of fine fibrils in epithelial cells that are anchored to the cytoskeleton. They were discovered by Rudolf Heidenhain, and first described in detail by Louis-Antoine Ranvier in 1897.
Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is named after Earl W. Netherton (1910–1985), an American dermatologist who discovered it in 1958.
The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins which binds neuropeptide S (NPS). It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Mutations in this gene have also been associated with this disease.
Trichorrhexis invaginata is a distinctive hair shaft abnormality that may occur sporadically, either in normal hair or with other hair shaft abnormalities, or regularly as a marker for Netherton syndrome. The primary defect appears to be abnormal keratinization of the hair shaft in the keratogenous zone, allowing for intussusception of the fully keratinized and hard distal shaft into the incompletely keratinized and soft proximal portion of the shaft.
Meesmann corneal dystrophy (MECD) is a rare hereditary autosomal dominant disease that is characterized as a type of corneal dystrophy and a keratin disease. MECD is characterized by the formation of microcysts in the outermost layer of the cornea, known as the anterior corneal epithelium. The anterior corneal epithelium also becomes fragile. This usually affects both eyes rather than a single eye and worsens over time. There are two phenotypes, Meesmann corneal dystrophy 1 (MECD1) and Meesmann corneal dystrophy 2 (MECD2), which affect the genes KRT3 and KRT12, respectively. A heterozygous mutation in either of these genes will lead to a single phenotype. Many with Meesmann corneal dystrophy are asymptomatic or experience mild symptoms.
The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family.
ORMDL sphingolipid biosynthesis regulator 3 is a protein that in humans is encoded by the ORMDL3 gene. This gene is associated with asthma in childhood. Transgenic mice which overexpress human ORMDL3 have increased levels of IgE. This correlated with increased numbers of macrophages, neutrophils, eosinophils, CD4+ and enhanced Th2 cytokine levels in the lung tissue.
The CARD-CC protein family is defined by an evolutionary conserved "caspase activation and recruitment domain" (CARD) and a coiled-coil (CC) domain. Coiled-coils (CC) act as oligomerization domains for many proteins such as structural and motor proteins, and transcription factors. This means that monomers are converted to macromolecular complexes by polymerization. In humans and other jawed vertebrates, the family consists of CARD9 and the three "CARD-containing MAGUK protein" (CARMA) proteins CARD11 (CARMA1), CARD14 (CARMA2) and CARD10 (CARMA3). Although the MAGUK protein DLG5 contains both a CARD domain and a CC domain, it does not belong to the same family as the CARD-CC proteins since the evolutionary origin of its CARD domain is very likely to be different.
Brian S. Kim is the Sol and Clara Kest Professor, Vice Chair of Research, and Site Chair of Mount Sinai West and Morningside in the Kimberly and Eric J. Waldman Department of Dermatology at Icahn School of Medicine at Mount Sinai. He is also Director of the Mark Lebwohl Center for Neuroinflammation and Sensation.
| Authority control databases: Academics |
|---|
