Détails de la réservation
- Le : 1 March 2018
- De : 11 h 00
- à : 12 h 30
- Salle : Salle de conférence
Détails de l'évènement
David Kelsell
Professor of Human Molecular Genetics, Blizard Institute, Barts and the London Medical School,
Queen Mary University of London
" iRhom2 and the keratinocyte stress response"
Résumé
The ability of cells and tissues to withstand and respond to a variety of stressors is fundamental to life. In mammals, the skin plays a unique role in the defence against external damage, pathogens and allergens, and therefore displays many specialised adaptations to environmental stress. In particular, the epidermis of palmoplantar (palm and sole) regions is uniquely adapted to withstand remarkable physical stress. We have identified dominantly-inherited point mutations in the gene encoding iRhom2 (RHBDF2) associated with Tylosis with Oesophageal Cancer, a syndrome in which affected individuals develop focal palmoplantar keratoderma (PPK) and have a very high risk of oesophageal squamous cell carcinoma. We have shown these point mutations to result in gain-of-function of the iRhom2 protein, a catalytically inactive member of the rhomboid family. Based on multiple lines of evidence generated by our laboratory, this proposal hypothesises that iRhom2 functions as a major regulator of the response to cellular stress and disease in the epidermis. Our work has shown iRhom2 to be an important regulator of keratin dynamics, the epidermal barrier and growth factor / cytokine production via regulation of the sheddase ADAM17. This talk will discuss the role of iRhom2 in regulating epidermal keratin dynamics in response to stress and will describe signalling pathways both upstream and downstream of iRhom2.
Invitation Alain Taïeb – Inserm U 1035
Responsable
- Nom : Rocher Virginie