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

肺部疾病，特别是肺癌，是人类死亡的主要原因之一。肺内稳态的破坏是这些病理的基础。肺泡上皮是气体交换发生的区域。因此，维持适当的形态和细胞组成是肺功能的关键事件。肺上皮细胞的更新是一小群称为肺干/祖细胞的细胞的责任，这些细胞具有分化成肺泡上皮细胞的任何细胞类型的潜力。然而，对肺干细胞知之甚少，直到最近才被分离出来。我已经能够分离肺干/祖细胞并培养它们。利用这个系统，我计划研究参与调节肺干细胞稳态的机制。我也将寻找标记物，可用于检测和斑点这些细胞在体外和invivo. In调节肺干细胞的机制的深入表征将有可能控制他们的命运，自我更新或生产肺泡上皮细胞通过操纵一些特定的蛋白质。将这些发现转移到人类身上将为肺部疾病的研究和治疗开辟新的途径。

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.