Â鶹AV

Research Focus

Patients with acute respiratory distress syndrome (ARDS) are placed on mechanical ventilators to improve oxygenation, but the ventilator may cause additional injury to the lungs due to either overdistention or airway collapse and reopening. Clinical trials have demonstrated a substantial reduction in mortality in ARDS patients when ventilation strategies are used that reduce overdistention (lower tidal volumes) and minimize airway collapse and reopening (positive end expiratory pressure). The lung is a mechanically dynamic organ, and cells in the lung are subjected to shear stress due to fluid flow, tensile and compressive forces due to respiratory motion, and normal forces due to vascular or airway pressure. High tidal volume mechanical ventilation in injured lungs induces mechanical stresses that increase injury to the lung epithelium, stimulate inflammatory responses, and decrease repair mechanisms.  In addition, pulmonary fibrosis results in changes in the mechanical properties of the lungs that profoundly impact gas exchange.  We are focusing on the mechanisms by which mechanical forces contribute to lung injury, inhibit wound healing of lung epithelial cells, and stimulate inflammation. We are examining signaling pathways related to injury and repair, pulmonary fibrosis, cell migration and wound healing, inflammasome activation, cytoskeletal remodeling, stimulation of reactive oxygen species, cytokine secretion, and regional variations in cellular tension. In addition, we are examining lung injury in vivo and the effects of exposure to high levels of oxygen (hyperoxia). My research seeks to elucidate the molecular mechanisms of lung injury, repair, and remodeling, and to develop approaches to reduce lung disease.