Dr Diana Blaydon, BSc, PhD
Email: email@example.comTelephone: +44 20 7882 2340
After obtaining a BSc in Biochemistry from the University of Bath, I worked in the Molecular Genetics Unit at the Institute of Child Health, UCL, during which time I also completed a PhD on the molecular genetics of Usher syndrome (hearing loss in combination with retinitis pigmentosa). In 2004 I joined the Centre for Cell Biology and Cutaneous Research in the Blizard Institute as a postdoc in Professor David Kelsell’s lab, investigating the genetic basis of rare inherited skin diseases. In September 2013 I started working as a non-clinical lecturer in the Blizard Institute.
My research is centred around understanding epidermal barrier function, primarily through the identification of the underlying cause of rare inherited skin disorders, coupled with functional studies to aid understanding of both the underlying disease mechanism as well as the normal biology of the skin.
Problem Based Learning facilitator for School of Medicine and Dentistry MBBS programme.
The epidermis of the skin is a highly specialized stratified epithelium that forms an essential barrier between the body inside and the environment outside, preventing water loss, whilst excluding foreign substances and organisms.
In order to aid our understanding of the physiology of the epidermal barrier, we seek to identify the underlying cause of rare skin diseases that manifest as barrier defects.
Current research projects build upon recent novel causative genes identified and include:
- Understanding the role of the water-channel protein aquaporin-5 (AQP5) in normal and disease skin.
We recently identified mutations in AQP5 as the underlying cause of an autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma (NEPPK), a skin disease characterised by a diffuse, even thickening of the epidermis on the palms and soles along with an outside-in barrier defect as indicated by the white spongy appearance adopted by affected skin upon exposure to water for short periods of time. Prior to this finding, expression of AQP5 in the skin was believed to be restricted to cells of the eccrine sweat glands located in the dermis. The function of AQP5 in epidermal keratinocytes is currently unknown, but the diffuse NEPPK patient phenotype indicates that AQP5 has a role in the establishment and/or maintenance of the epidermal barrier, particularly in the highly specialized epidermis of the palms and soles (palmoplantar) which is exposed to increased levels of mechanical stress.
- The role of the iRHOM2-ADAM17 axis in repair and regeneration of the oesophageal barrier.
We recently identified mutations in iRHOM2 as the underlying cause of Tylosis, an inherited condition in which affected individuals exhibit thickened skin on palms and soles in combination with lesions of the mucosa in the mouth and oesophagus and an increased lifetime risk for oesophageal cancer. We have shown how iRHOM2, an inactivate member of the Rhomboid family of membrane serine proteases, contributes to repair and regeneration of barrier function in the skin via its regulation of ADAM17 maturation and activity. Tylosis patients exhibit a wound healing defect in both the skin and the oesophagus, another stratified epithelium, highlighting the importance of iRHOM2 in the integrity of both of these barriers. We aim to understand the role of the iRHOM2-ADAM17 axis in repair and regeneration of the normal oesophagus epithelial barrier and investigate if it is compromised in patients with gastro-oesophageal reflux disease (GORD), in which the persistence of a defective oesophageal barrier function appears to be a major underlying factor.
At the same time we continue to perform exome sequencing on DNA from patients with rare, inherited skin disorders in a bid to identify additional disease-causing variants in novel genes.
Blaydon DC, Lind LK, Plagnol V, Linton KJ, Smith FJ, Wilson NJ, McLean WH, Munro CS, South AP, Leigh IM, O'Toole EA, Lundström A, Kelsell DP (2013) Mutations in AQP5, Encoding a Water-Channel Protein, Cause Autosomal-Dominant Diffuse Nonepidermolytic Palmoplantar Keratoderma. Am J Hum Genet; 93(2):330-335.
Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, Bishop DT, Ellis A, Jankowski J, Field JK, Leigh IM, South AP, Kelsell DP (2012) RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet; 90(2):340-6.
Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, O'Toole EA, Martin JE, Lindley K, Vulliamy T, Abrams DJ, MacDonald TT, Harper JI, Kelsell DP (2011) Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med; 365(16):1502-8.
Blaydon DC, Nitoiu D, Eckl KM, Cabral RM, Bland P, Hausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP (2011) Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet; 89(4):564-71.
Blaydon DC, Ishii Y, O'Toole EA, Unsworth HC, Teh MT, Rüschendorf F, Sinclair C, Hopsu-Havu VK, Tidman N, Moss C, Watson R, de Berker D, Wajid M, Christiano AM, Kelsell DP (2006) R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signalling, is mutated in inherited anonychia. Nat Genet; 38(11):1245-7.
Lisa McGinty – PhD Student