Alan Ardito

Plasmodium falciparum malaria is a global challenge, responsible for approximately 619,000 deaths in 2022, with most fatalities being children under five. Cerebral malaria (CM) is a severe form of the disease characterized by fevers, comas, seizures, and a high fatality rate. Survivors are often left with cognitive and behavioral disabilities. CM pathogenesis involves infected red blood cells adhering to brain microvasculature and blood-brain barrier dysfunction (BBB). We propose that the parasite protein PfPIESP2 induces BBB breakdown by interacting with human EphA2, a receptor crucial for BBB integrity. Preliminary data show that PfPIESP2 permeabilizes brain endothelial cells and binds to EphA2. We hypothesize that infected red blood cells sequester in the brain, where PfPIESP2-EphA2 interaction leads to BBB breakdown. To test this hypothesis, we will study PfPIESP2’s effects on endothelial cells and validate its human binding partners.