The global COVID19 pandemic has highlighted the lethality and morbidity associated with infectious respiratory diseases. These diseases can lead to devastating syndrome known as the acute respiratory distress syndrome (ARDS) where bacterial/viral infections cause excessive lung inflammation, pulmonary edema, and severe hypoxemia (shortness of breath). Although ARDS patients require artificial mechanical ventilation, the complex biofluid and biomechanical forces generated by the ventilator exacerbates lung injury leading to high mortality. My group has used mathematical and computational modeling to both characterize the complex mechanics of lung injury during ventilation and to identify novel ways to prevent injury at the cellular level. We have used in-vitro and in-vivo studies to validate our mathematical predictions and have used engineering tools to understand the biological consequences of the mechanical forces generated during ventilation. In this talk I will specifically describe how our mathematical/computational approach has led to novel cytoskeletal based therapies and how coupling mathematics and molecular biology has led to the discovery of a gene regulatory mechanisms that can minimize ventilation induced lung injury. I will also describe how we are currently using nanotechnology and gene/drug delivery systems to enhance the lung’s native regulatory responses and thereby prevent lung injury during ARDS.