The SLC superfamily of membrane transporters play critical roles in many aspects of human physiology and pharmacology. Several SLC transporters play roles in drug transport. Of note, nucleoside transporters are important contributors to nucleoside physiology, making them desirable targets to modulate nucleoside-mediated cell signaling. Further, nucleoside transporters control the cellular uptake of nucleoside-analog anticancer drugs and serve as predictive markers of patient response to such chemotherapies. To gain deeper understanding of the functional mechanisms exhibited by these membrane transporters, we propose to pursue cryo-EM studies to elucidate structures of these transporters in various conformational states as well as in complex with various drugs. Our studies will provide the platform to develop therapeutics against cancer or ischemia-reperfusion injury.