Regulation of lung stem cells in homeostasis and tumorigenesis. Role of Stress-Activated Protein Kinases

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Lung diseases and specially lung cancer, are among the more prevalent and one of the first causes of mortality in humans. Dysruption of lung homeostasis is underlying these pathologies. The alveolar epithelium is the area where gas exchange takes place. Thus the maintenance of the proper morphology and cellular composition is a key event for lung function. The turnover of lung epithelia is responsibility of a small group of cells named lung stem/ progenitor cells that have the potentiality to differentiate into any of the cell types of the alveolar epithelia. However, very little is known about lung stem cells and only recently have been isolated. I have been able to isolate lung stem/progenitor cells and culture them. Using this system I plan to study the mechanisms involved in the regulation of lung stem cell homeostasis. I will also search for markers that may be used for the detection and spotting of these cells in vitro and in vivo.In-depth characterisation of the mechanisms regulating lung stem cells will make possible controlling their fate to self-renewal or production of alveolar epithelia by manipulation of some specific proteins. Transferring of these findings to humans will open new ways in the study and therapy of lung diseases.