Circadian-coupled Cellular and Lung Function in COPD
Acute CS exposure reduces activity, but does not affect phase angle of entrainment or activity consolidation. Representative double-plotted actograms showing considerable reduction in locomotor activity of acute (10 days) CS-exposed mice (right panel) relative to air-exposed mice (left panel). Gray shading indicates the relative dark pahse (ZT12-24). During the periods of CS exposure (ZT3-ZT9), activity was not recorded (black stars).
The major goals of this translational T1 proposal is to elucidate the role of peripheral circadian periodicity genes/proteins-CLOCK, BMAL1 and Period2 in regulating lung cellular, molecular and physiological functions in pathogenesis of COPD, and deficiency or posttranslational modifications of circadian proteins lead to loss of efficacy of steroids and β2-agonists in patients with COPD and during its exacerbations, and strategic chronotherapeutic manipulation of circadian proteins.« back to all projects