Grant: CIHR Fellowship

Acute lung injury (ALI), and the more severe acute respiratory distress syndrome (ARDS), are life-threatening conditions of the lung for which there are currently no effective treatments. General supportive measures like mechanical ventilation are the mainstay of treatment; however, mortality remains unacceptably high at between 30-50%. The annual incidence of ALI/ARDS has been estimated at up to ~64 cases per 100,000 persons in the US, representing a significant healthcare burden that costs more than $5 billion (US) annually. The impact of ALI/ARDS has become even more pertinent, as this condition is the primary cause of severe illness and death in people suffering from the H1N1 "swine" flu and other viral pneumonias (e.g., SARS). Thus, there is an urgent need to develop more effective therapeutic options. ALI/ARDS occurs when the lung airspace becomes flooded with fluid and other debris that has leaked out of blood vessels. These fluid-filled lungs make it extremely difficult to breathe, which can lead to severe medical complications often with grave consequences for the patient. At the molecular level, there is evidence to suggest that these leaky blood vessels may be caused by abnormally high levels of a specific blood vessel growth factor, known as angiopoietin-2 (Angpt-2). The proposed research will probe the function of Angpt-2 by employing several strategies designed to block the activity of Angpt-2 or decrease its production. The potential therapeutic merits of these approaches will be evaluated in mouse models of ALI, which can provide valuable insight into the corresponding human conditions. It is anticipated that these strategies may not only form the basis for a novel therapeutic strategy, but will also enhance our understanding of the underlying causes of ALI/ARDS.