Athar Chishti

Our laboratory is conducting research on the assembly and regulation of the mammalian cytoskeleton with a focus on diseases that afflict red blood cells and platelets, such as malaria, babesiosis, sickle cell disease, and thrombosis. Malaria is one of the most common infectious diseases, and ~627,000 people, mostly African children, die each year due to complications of malaria (WHO Estimate for 2020). We are studying the molecular mechanisms of host-pathogen interactions in the malaria parasite infected red blood cells (iRBCs). The specific focus is on the surface protrusions called knobs in Plasmodium falciparum infected human iRBCs. Knobs are critical for the adhesion of iRBCs to host endothelial cells in the brain and placenta. Previously, we identified human erythrocyte Band 3 (anion exchanger-1 or SLC4A1) and the Glycophorin A complex as crucial co-receptors for malaria parasite surface proteins involved in the pathogen entry in host cells. Parasite proteins and their cognate host receptors are essential for the development of new therapeutics as well as an effective multi-subunit vaccine. We generated calpain-1 null mice with sickle cell disease (SCD) revealing a functional role of cysteine proteolysis in SCD and thrombosis. Additionally, our lab has generated several mutant mouse models of Dematin/Protein 4.9, P55/MPP1, Kinesins KIF13B/A, and Band 3. Some of these models are currently used for mechanistic studies in both erythroid and non-erythroid cells.