Main scientific projects:
The team’s interests concern the molecular mechanisms that control epithelial physiopathology, mainly (1) to identify the genes and signalling pathways involved in the normal and pathological embryonic ectodermal commitment and epithelial differentiation, (2) to evaluate the potential of human embryonic stem cells and iPS for cell therapy and cellular models for pathologies. Methodologies includes transcriptome and microRNA profiling coupled to functional genomic approaches (siRNA in vitro and in vivo), cell biology and organotypic reconstitution.
Project 1. Development, stem cells and p63 (D. Aberdam/M. Rouleau/Shoham Arad/Zohar Wolchinsky):
We designed a protocol that induces ES cells to recapitulate in vitro the main steps of embryonic epithelial development. It allows the identification of otherwise inaccessible molecular events that normally occur in utero. This cellular model is used to characterize, in a frame of an European network project (Epistem), the functions of each p63 gene isoform and their related pathways in normal ectodermal commitment, epidermal fate and in rare ectodermal dysplasia syndromes. We recently discovered a new function of TAp63 in early cardiogenesis through an endodermal paracrine effect. The general circuitry controlled by p63 in the embryonic endoderm is currently studied by global molecular approaches (Chip-seq,...) and functional studies in Xenopus.
(main recent publications)
Project 2. Potential of human ES and iPS cells for cell therapy:
(D. Aberdam/I. Petit//Ruby Shalom-Feuerstein/E. Aberdam/Nava Salmon):
We aim to evaluate the potential of human ES and iPS cells as an alternative therapy for epithelial cell deficiencies. Optimal culture conditions to differentiate huES into ectodermal precursors (for corneal, epidermal but also endodermal pancreatic cells) will be defined, and implicated genes and signaling pathways will be characterized. In parallel, we will evaluate the differentiated cells for both graft take and potential immune response of the host.
Reprogamming (iPS) of somatic cells from patients affected by Ectodermal Dysplasia syndromes and Schizophrenia is currently under process to design, through epidermal and neural differentiation, unique cellular models for basic reseach and drug design applications. (recent publications)
