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Study of epithelial stem cells, pathophysiology and therapy (Epi-Patho-Stem)
Date du début: 1 sept. 2013, Date de fin: 31 août 2017 PROJET  TERMINÉ 

The stratified epithelium of the skin (epidermis) and the cornea share common characteristics in term of structure, function and developmental origin. These tissues which line the external surface of the mammalian body and eye are multi-layered tightly packed tissues providing protection against infections, injuries and water loss. Although skin stem cell therapy have been firstly reported 3 decades ago, in 1984, ex vivo expansion of stem cell and the maintenance of their multi potency is poor. Consequently, grafts are totally deficient of hair follicles, sweat and sebaceous glands which are essential for functionality. Additionally, investigation of the embryonic events that accompany human congenital diseases is limited due to ethical issues and the lack of appropriate models. Therefore, a better understanding of the molecular circuitry that underlies these biological processes is essential for designing innovative therapeutic approaches.My lab will be devoted to exploring the mechanisms of regulation of stem cell homeostasis, and pathophysiology of the skin and the cornea. In my previous studies, we have generated a new induced pluripotent stem cell (iPSC) model for skin and corneal pathophysiology, and identified microRNAs that are required for epithelial stem cell regulation and lineage commitment. In addition, we unraveled a subset of genes that are regulated by p63 during embryonic development. Here we aim to (i) investigate the role of microRNA and p63-pathways in epithelial development and stem cell maintenance, (ii) generate and explore patient-specific iPSC as a new model for the research of genetic diseases, and (iii) develop innovative therapeutic approaches based on iPSC, gene therapy and pharmacology. Altogether, our study will provide insightful mechanistic details on epithelial lineage commitment and stem cell regulation in physiological conditions and pathology, and will pave the way for therapy.