Parasites are microorganisms that live within hosts and rely upon them to provide a plethora of nutrients essential for the survival of the microbe. Hence, a core requirement of the parasitic mode of existence is the ability to efficiently acquire nutrients from both the vertebrate host and the invertebrate vector, usually an insect. Our laboratory focuses on parasite membrane transporters, which are polytopic integral membrane proteins that mediate the uptake of specific nutrients from the extracellular environment. We employ a broad array of approaches, including biochemistry, molecular biology, genetics, cell biology and microscopy, proteomics, chemical biology, computational biology, pharmacology, etc. to investigate these transport processes at the molecular and cellular levels. Indeed we address a wide range of scientific problems, ranging from detailed molecular studies probing the mechanism of transporter function to physiological investigations to discern the biological roles of transporters in the intact parasites. Such diverse and interdisciplinary studies require close collaborations with various other laboratories both at OHSU and at other locations around the world. Furthermore, our laboratory promotes close interactions and collaborative work between members of our group as well as with collaborators elsewhere.
The organisms we study most intensely include several species of Leishmania parasites, responsible for the widespread group of neglected infectious diseases called leishmaniases, which afflict an estimated 12 million people globally. We also work extensively on the related African trypanosomes, Trypanosoma brucei, that cause African sleeping sickness. Additional studies are focused upon transporters of the malaria parasite Plasmodium falciparum, which causes close to 1 million deaths per year and represents one of the most burdensome infectious diseases worldwide.
Traditionally, our research has focused upon the basic biology and biochemistry of these parasites, attempting to understand how they acquire nutrients from their hosts and why specific nutrient uptake systems are critical to their biology. More recently, we have also become involved in drug discovery against each of these parasites, either by targeting essential transporters for compounds that selectively inhibit their transport activity or by screening large chemical libraries for compounds that kill the parasite by any mode of action (phenotypic screens).