Research in the Kyle lab focuses on the discovery, development, and mechanism(s) of resistance to anti-parasitic drugs. At present we focus on malaria, the most important parasitic disease of man, and the spectrum of diseases caused by pathogenic free-living amoebae, perhaps the most neglected of all tropical parasitic diseases. The overarching objectives of our research is to develop new tools to prevent disease, to train a new generation of parasitologists, to foster multidisciplinary research on tropical diseases, and to implement our findings to reduce the burden of parasitic diseases in endemic countries.

New drugs are urgently needed to combat malaria, primarily due to the emergence of drug resistance to one or more drugs - a phenomenon known as multidrug resistance. In addition, new drugs are needed that target the dormant hypnozoite stage of vivax malaria that can persist in the liver for weeks to months to years before activating to cause relapsing malaria. With funding from the Bill and Melinda Gates Foundation we have developed a novel system that permits long term maintenance of primary hepatocyte physiology in vitro and have used this technology to develop the first 384 well high content imaging assay to discover anti-hypnozoite drugs.

Elucidating mechanism(s) of resistance and discovering new drug treatment regimens, combinations, or strategies to overcome resistance is a second major research focus. Our studies have demonstrated novel phenotypes that allow P. falciparum to become resistant to artemisinin drugs. In addition, we’ve shown that cryptic mitochondrial heteroplasmy is the mechanism underlying resistance to atovaquone and other drugs that target the mitochondria of P. falciparum.