The Stuart Lab is focused on diseases that are caused by three related parasitic protozoa (Human African trypanosomiasis [sleeping sickness], Chagas disease and leishmaniasis) and on malaria, which is caused by another protozoan parasite. The lab investigates molecular and cellular processes of trypanosomes and Leishmania, because this can lead to the development of drugs for these parasitic diseases. The lab is also is studying immune responses in clinical trials of malaria vaccines.
RNA editing is essential to the survival of trypanosomes and Leishmania, but it does not occur in humans and it is thus being investigated as a target for the development of anti-parasitic drugs. Research in the lab on editing has stimulated discoveries on different types of RNA editing of medical importance by others in the field. The lab determined the molecular mechanism of editing, identified and characterized the molecular machinery, showed that it is essential in the disease stage and validated several of its components as therapeutic targets. Current studies are characterizing the structure and functions of multiple proteins of the editing machinery in detail and the regulation of processes for the purpose of drug development.
The lab is using a cell-wide systems biology approach to elucidate critical cellular processes in trypanosomatid parasites that can be exploited for the development of drugs against three related parasites: Trypanosoma brucei, T. cruzi and Leishmania species. The lab played a leading role in forming the consortium that sequenced and annotated the genomes of these parasitic pathogens; extended this work through high-throughput proteomic and functional genetic studies; identified and validated many drug targets; and created a consortium to develop drugs for these parasitic diseases. Ongoing studies include collaborations with medicinal chemists who test numerous compounds for their activity against the drug targets and their potential for development into drugs that may move onto clinical trials.
The lab pioneered research on the process of antigenic variation in trypanosomes, which these parasites use to evade elimination by the immune system, thus preventing the development of a vaccine. The lab recently discovered a molecular system that controls the expression of hundreds of surface protein genes in a stage where the parasites only produce one of these at a time. It showed that phosphoinositol metabolites control both the expression of the genes and antigenic switching. Ongoing studies are investigating the mechanisms by which these two processes are controlled; they indicate that complex epigenetic processes including intracellular signaling and molecular interactions within chromosomes are involved.
The lab leads a multi-institutional U19 research program on human immune responses to malaria infection and immunization, which is part of the NIH Human Immunology Project Consortium. Current studies are focused on immune profiling and systems biology approaches in immunology to study the human immune responses to Plasmodium falciparum infection and subunit and attenuated malaria vaccines. Insights gained from this research will have potential for impacting strategies for vaccine development and for treating immune-related diseases more broadly.
About Dr. Ken Stuart
Ken Stuart, PhD, is an affiliate professor of global health and chaired the Department of Pathobiology at the University of Washington from 1996 to 2004. He is also an affiliate investigator in the Vaccine and Infectious Disease Division at Fred Hutch. Stuart received a BA in biology from Northeastern University, Boston (1963), a MA in biology from Wesleyan University, Middletown, Connecticut (1965) and a PhD in zoology from the University of Iowa, Iowa City (1969). He received postdoctoral training in biochemistry at the National Institute for Medical Research, London (1969–70) and SUNY Stony Brook (1970–72) before becoming an assistant professor of biology at the University of South Florida (1972–76) prior to moving to Washington in 1976 to found the Center for Infectious Disease Research. He is an expert on the molecular and cell biology of parasitic pathogens and is known for his groundbreaking studies of RNA editing, a novel fundamental genetic process. He led a consortium for the discovery of drugs for parasitic diseases and was a leader in an international consortium that sequenced and interpreted the genomes of three related parasites.