Genetically inherited skin disease

David Kelsell PhD

Research field

The main research focus of David Kelsell's research group is the identification of the genetic and molecular mechanisms underlying epidermal disease. These studies have identified the important role of proteins involved in the regulation and formation of epidermal cell junctions specifically gap junctions, adherens junctions and desmosomal junctions. These junctions are responsible for cell-cell adhesion, cell signalling and communication, key properties to maintain the normal cellular phenotype and tissue architecture. For example, we were the first to identify Connexin 26 mutations associated with non-syndromic hearing loss, the major cause of genetic hearing loss worldwide. Connexins are the major proteins of gap junctions. In addition, we were the first to describe mutations in Desmoplakin, the major protein of the desmosome, with inherited skin disease and cardiomyopathy. Current grant support is from the BBSRC, National Eczema Society, BDF Newlife, Association of International Cancer Research, the Wellcome Trust and Cancer Research UK .

Current research programmes are:

1 The genetic and molecular events occurring in Basal Cell Carcinoma

2 The role of connexins in skin disease and deafness: functional consequences of mutations

3 The genetic and epidemiological investigation of atopic eczema in the Bangladeshi population of east London .

4 The role of ABCA12 in the skin disease Harlequin ichthyosis and epidermal biology.

Key research papers

1 Muy-Teck T, Blaydon D, Chaplin T, N J, S Skoulakis S, Harwood CA, Proby CM, Philpott MP, Young BD and Kelsell DP. Genome-wide SNP Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic Event. Cancer Research 2005 (in press).

2 Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA, Dopping-Hepenstal PJ, Dale BA, Tadini G, Fleckman P, Stephens KG, Sybert VP, Mallory SB, North BV, Witt DR, Sprecher E, Taylor AE, Ilchyshyn A, Kennedy CT, Goodyear H, Moss C, Paige D, Harper JI, Young BD, Leigh IM, Eady RA, O'Toole EA.Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.Am J Hum Genet. 2005 May;76(5):794-80

3 Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM. Connexin 26 mutations in hereditary non syndromic sensorineural deafness. Nature 1997 387:80-3