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Identification and functional analysis of the genes involved in junctional epidermolysis bullosa: disorders affecting adhesion of epithelial cells

Objective

- To characterise the structural organisation and analyse the functional role and regulation of the genes involved in junctional epidermolysis bullosa (JEB).
- To sample and diagnose JEB patients.
- To identify the candidate genes and the genetic mutations involved in JEB.
- To establish a correlation between the genetic abnormalities and the defined clinical JEB phenotypes.
- To extend the prenatal diagnosis of pregnancies at risk for JEB to new candidate genes.
- To perform the structural and functional analysis of the proteins affected in JEB.
- To establish model systems useful in the analysis of the adhesion and wound healing processes in epithelia.
- To develop strategies for somatic gene therapy of keratinocytes with genetic defects in multifunctional and structural adhesion proteins.

The study of the pathophysiological processes which underlie the extensive epithelial-mesenchymal dysadhesion observed in patients affected by junctional epidermolysis bullosa (JEB) has set the stage for the comprehension of the mechanisms of adhesion and migration of epithelial cells. JEB keratinocytes constitute an invaluable tool to dissect the mechanisms of cell adhesion, since the different clinical manifestations of the disease appear to be linked to mutations affecting cellular receptors and their extracellular ligands.

The cooperation among the five laboratories with complementary experience and expertise will permit a comprehensive analysis of the pathophysiology of junctional bullous diseases by all the possible approaches of molecular genetics, cell biology and biochemistry. Results of this research will provide a better comprehension of the mechanisms of adhesion and migration of epithelial cells and will allow : 1) The development of new diagnostic tools, and new knowledge of epithelial cell adhesion and migration in wound healing and invasive pathologies; 2) New and effective forms of treatment by the development of somatic gene therapy that will reverse the clinical consequences of these devastating skin diseases; 3) The development of therapies for common autoimmune blistering skin diseases in which the same structural proteins are target autoantigens; 4) A benefit of research focused on more effective treatment of patients with burn injuries and chronic ulcers requiring epithelial grafting.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Avenue De Valombrose 28
06107 Nice
France

Participants (4)

Istituto Dermopatico dell'Immacolata
Italy
Address
104,Via Monte Di Creta
00167 Roma
Laboratorio di Ingegneria dei Tessuti
Italy
Address
83-85,Via Dei Castelli Romani 83-85
00040 Ardea
THE NETHERLANDS CANCER INSTITUTE / ANTONI VAN LEEUWENHOEK HOSPITAL
Netherlands
Address
121,Plesmanlaan 121A, Van Leeuwenhoek Ziekenhuis
1066 CX Amsterdam
Westfälische Wilhelms - Universität Münster
Germany
Address
56,Von-esmarsch-straße
48149 Münster