Malaria remains a major public health issue, and resistance to most current treatments is widespread. Current efforts for the worldwide eradication of this ancient disease include the establishment of new strategies to block the transmission of malaria parasites to the mosquito. One of the key properties of malaria transmission stages is their enrichment in deep tissues, i.e., the brain, during development in humans. We are working toward a comprehensive analysis of transmission stage tissue enrichment, and of the underlying mechanisms of this enrichment in a laboratory setting. This work includes field collaborations in Blantyre, Malawi and Ibadan, Nigeria.

P. falciparum erythrocyte membrane protein 1 (PfEMP) is localized on the infected red blood cell (RBC) surface. PfEMP1 is encoded by the var multigene family and it represents a major parasite virulence factor due to its central role in parasite sequestration and immune evasion. There is increasing evidence that the differential binding properties of PfEMP1 variants to specific host receptors are directly linked to the cytoadherence of infected RBC (iRBC) to the microvascular endothelium. We are using transgenic parasite lines expressing PfEMP1 virulence domains to gain a better understanding of the link between the expression of PfEMP1 and pathology.

During the cycle in human red blood cells, the parasite induces drastic morphological changes of its host cell. This mechanism of host cell remodeling serves to induce cytoadherence of iRBCs to host vascular endothelium, to facilitate nutrient import and immune evasion. The recent identification of a conserved motif required for export of virulence and remodeling factors from the parasite to the host allowed a classification of the exportome in P.falciparum and other Plasmodium species. A comparative functional analysis of exported proteins in different Plasmodium species allows us to investigate the evolution of virulence in malaria parasites on a molecular and cellular level.