Dr. Sayner’s research project focuses on understanding why endothelial cells that line the blood vessels of the pulmonary circulation act abnormally during acute respiratory distress syndrome (ARDS), an important cause of respiratory failure.
“When blood bicarbonate becomes elevated – as it can in respiratory disorders – it not only alters pH, but it can also activate an enzyme called soluble adenylyl cyclase,” Dr. Sayner said. “When this enzyme is activated in microvascular endothelial cells, it makes the blood vessels leaky, allowing fluid to get into the airspaces and restrict gas exchange.”
This project examines the transporters that deliver bicarbonate from the blood into the endothelial cells and will determine how these transporters are regulated during sepsis, a common cause of ARDS. Dr. Sayner's research team is also investigating the cellular mechanisms that promote the bicarbonate-induced barrier disruption.
“While much has been learned about ARDS, there are no pharmacological therapies that improve patient outcomes and the current standard of care is supportive therapy,” Dr. Sayner said. “Understanding how bicarbonate signaling regulates the integrity of the pulmonary endothelial barrier will help guide clinicians in the therapeutic management of blood bicarbonate levels and could also provide novel pharmacological targets to better treat ARDS.”
