Current Research and Scholarly Interests
Severe malaria caused by Plasmodium falciparum is a leading cause of morbidity and mortality in the developing world, particularly among young children and pregnant women. Population genetic studies dating back to the mid-20th century first proposed that erythrocytes (red blood cells), the host cell for P. falciparum, have been under natural selection due to malaria. Hemoglobinopathies, thalassemias, ovalocytosis, and G6PD deficiency are all examples of red cell disorders that appear to provide protection against severe malaria.
Although the notion that malaria has helped shape the human genome is well- accepted, the lack of a nucleus in human erythrocytes has hindered our ability to study genetic interactions between these unusual host cells and P. falciparum parasites. Recently, we developed a hematopoietic stem cell-based approach to tackle this issue, in which we can genetically alter nucleated hematopoietic precursor cells and differentiate them ex-vivo to mature erythrocytes that can be infected by P. falciparum. Using this approach, we performed a forward genetic screen of human blood groups to identify critical host factors for P. falciparum, and discovered several candidates that appear to be required for efficient parasite invasion of red blood cells. We found that the Cromer blood group antigen CD55 (DAF) is essential for parasite invasion and is necessary for proper attachment of merozoites to the erythrocyte surface. Importantly the requirement for CD55 appears to be strain-transcendent, suggesting that it may act as a critical receptor during malaria infection.
We are currently pursuing fundamental questions related to host-pathogen interactions in malaria, with the host erythrocyte as a focal point. We employ a variety of approaches spanning molecular parasitology, stem cell biology, cell biology, biochemistry and genomics. We welcome self-motivated individuals interested in joining us as we seek to learn more about the fascinating biology underlying host-pathogen interactions in malaria.
