Research Projects

Malaria-causing Plasmodium parasites cause significant global disease burdens. They must infect erythrocytes, which must develop through the liver stage of infection. When transmitted by mosquito bites, parasites exit the dermis, enter blood vessels, and travel to the liver, where they invade hepatocytes. This invasion is highly selective, and Plasmodium sporozoites cannot infect and develop within any other cell. The molecular underpinnings of why the parasite invades, grows, and develops within one cell, ultimately causing death and disease, and rejecting infection of another cell remain unknown. Recent research has shown that the trafficking of lysosomes to the host cell surface and fusion of these lysosomes with the plasma membrane likely proceeds sporozoite entry. The Genome-wide CRISPR/Cas9 approach has identified previously known and novel host receptors that facilitate invasion. The proposed hypothesis is that hepatocyte lysosome exocytosis modulates protein-protein interactions on the hepatocyte surface, determining a cell's susceptibility to Plasmodium infection. The molecular details that facilitate entry could inform interventions that block parasite entry and shape our understanding of the origin of cellular tropism of intracellular pathogens.