We are part of a team with Keith Burridge and Carla Cerami that have recently been funded by NIH to explore how malaria-infected red blood cells are taken up by the endothelial cells that line brain blood vessels. Understanding how this uptake may damage the endothelial barrier would significantly contribute to our understanding of cerebral malaria as well as identify potential therapeutic targets.
Malaria is caused through infection with the parasite Plasmodium falciparum and remains one of the largest global infectious disease burdens, infecting over 200 million and killing nearly 700,000 people annually. Of several possible disease manifestations, cerebral malaria has the worst survival outcomes. Cerebral malaria, characterized by coma and neurological deficits, is caused when parasitized red blood cells collect in the blood vessels feeding the brain. Collection in the blood vessels can lead to obstruction, limiting oxygen delivery to tissue, as well as inducing significant inflammation. While this process is linked to a breakdown in the blood-brain barrier, the molecular mechanisms that lead to vascular damage in cerebral malaria are not known. The long term goal for this work is to understand how parasitized red blood cells induce endothelial activation and blood-brain barrier breakdown in order to improve therapeutic development.