ROLE OF PI3K/AKT IN STRATIFIED EPITHELIA STEM CELL
- 5 Years 2006/2011
- 517.000€ Total Award
The cure of human inherited diseases will be possible when we will be able to genetically modify stem cells of patients, and to correct permanently their functional abnormalities. Only then, stem cells bearing the corrected genes will be able to regenerate healthy organs and tissues. To this end, it will be crucial to control and direct the long-term behavior of stem cells, and the cell progenies from them derived. Presently, very little is known about keratinocyte stem cell fate regulation, and their underlying biochemical signals. In stratified epithelia, these processes are especially obscure, thus delaying the development of gene therapy applications for the treatment of the genetic disorders of these tissues. This research project aims at elucidating the intracellular signals regulating keratinocyte stem cell biology, by investigating the role of an important group of enzymes, the PI3-kinase family, in the epidermis and the eye surface epithelia. By attempting to reveal the biochemical signals that regulate epithelial stem cells, this study aims to improve our ability to identify and manipulate stem cells, making possible their use for the gene therapy of severe genetic diseases affecting these tissues, such as Junctional Epidermolysis Bullosa, and Macular Corneal Dystrophy type II.
Scientific Publications
- 2015 NATURE COMMUNICATIONS
PI3K-C2 gamma is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling
- 2005 JOURNAL OF BIOLOGICAL CHEMISTRY
Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death
- 2015 EXPERIMENTAL DERMATOLOGY
Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints
- 2014 STEM CELLS
Nuclear Akt2 Opposes Limbal Keratinocyte Stem Cell Self-Renewal by Repressing a FOXO-mTORC1 Signaling Pathway
- 2007 DIFFERENTIATION
Foxn1 promotes keratinocyte differentiation by regulating the activity of protein kinase C