My laboratory has focused on the cell biology and physiology of the malaria parasite, Plasmodium falciparum. We are particularly interested in how malaria parasites acquire nutrients and other essential solutes from the human bloodstream. While growth inside human erythrocytes facilitates evasion of immune responses, it complicates acquisition of nutrients from serum. Many essential nutrients are not present in erythrocyte cytosol and have inadequate host cell permeability to sustain parasite demand. This problem had been recognized for decades, but the molecular mechanisms used to overcome it were unknown. My group identified two unusual ion channels that appear to resolve this dilemma. One of these channels, the plasmodial surface anion channel (PSAC), is present on the infected erythrocyte membrane but absent from uninfected cells. Its unique functional properties along with mutants we generated through in vitro selection strongly suggest PSAC is encoded by the parasite and trafficked out to the host membrane. Its strict conservation in all plasmodia suggests it may be a target for antimalarial development. Major ongoing areas of investigation in the laboratory include 1) identification of the genes responsible for PSAC and other parasite transport mechanisms with molecular, genetic, and biochemical approaches, 2) functional characterization of these transport proteins with the goal of understanding the permeation process, channel structure, and physiological roles, and 3) antimalarial drug discovery and development using novel, high-affinity PSAC antagonists.
Sanjay A. Desai, MD, PhD