Malaria is caused by protozoan parasites of the genus Plasmodium, among which Plasmodium falciparum is the most virulent species in humans. Malaria is still one of the most devastating infectious diseases, killing close to 1 million people each year, most of whom are infants and young children in Africa. The capacity of the parasite to develop drug resistance against existing drugs calls urgently for new strategies in drug development. P. falciparum invades and extensively remodels red blood cells. Our lab investigates kinase signalling pathways in the parasite and its host erythrocyte, with the ultimate aim to discover anti-malarial drug targets.
We have used an antibody array approach to compare the phosphorylation status of uninfected versus P. falciparum-infected host erythrocyte signalling molecules. We showed that a variant signalling pathway involving artythrocytic p21-activated protein kinase (PAK) and MAPK/ERK kinase (MEK) is strongly activated following infection, and we were able to show that proteins potentially involved in the regulation of eryptosis are differentially phosphorylated in infected and uninfected red blood cells and are potential affectors of this pathway.
Targeting host cell kinases would circumvent the potential development of drug resistance by the parasites. Additionally we would be able to capitalize on drug development within cancer research, as human kinases are being explored as important cancer drug targets.