egeorges_lab

Malaria Drug Resistance - Membrane transporters expressed at the digestive vacuole (DV) have been shown to confer resistance to several current antimalarials. Research over the past several decades have shown that mutations in P-gh1 and PfCRT are causative of drug resistance to structurally diverse drugs. Moreover, it has been shown that both P-gh1 and PfCRT have overlapping substrate specificities. However, while one transporter (P-gh1) transports drugs into the DV from the cytosol, the other transporter (PfCRT) transports drugs from the DV into the parasite cytosol. This latter point, together with overlap in substrate specificities of the two transporters, whereby toxic drugs (e.g., MK571, a quinoline-based drug) that are better substrates for P-gh1 but block PfCRT function can be used to target drug resistant parasites (see Figure 1).


In addition, give the essential physiologic roles of these membrane transporters (e.g., P-gh1 and PfCRT) for the parasite's survival and proliferation. The normal functions of P-gh1 or PfCRT, and their endogenous ligands, would expand potential of developing yet other novel antimalarials that target their normal functions.


Our research focuses on the molecular mechanisms of these transporters in antimalarials drug resistance and normal physiological functions. With regards to the latter we focusing on understanding the biochemistry and regulation of PfCRT.