In response to environmental injuries, adult lungs will reactivate a series of developmental important pathways, such as Hedgehog, TGF-beta, Wnt/beta-catenin and Notch pathways to fulfill the regeneration functions. We are interested to address how COPD GWAS genes regulate these developmental important pathways in postnatal stage thus modulate the lung repair/regeneration capacity upon chronic injuries in distal lungs. Functions of these GWAS genes, possibly triggering or balancing two or more these developmental pathways in lung progenitor cells will determine the fate of the diseases in response to different types of injuries that vary in type, duration and intensity.