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Stuart Lab

Research in the Stuart Lab is focused on protozoan pathogens and the diseases that they cause. These include malaria which is caused by Plasmodium parasites and Human African Trypanosomiasis (sleeping sickness), Chagas disease and Leishmaniasis that are caused by three Trypanosomatid parasites. The lab investigates molecular and cellular processes of the parasites and immune responses to infection and vaccines to develop drugs, vaccines and diagnostics that are needed. 

Malaria Immunology

The Stuart Lab co-leads a multi-institutional U19 research program on human immune responses to malaria, HIV and Covid infection and vaccination and is part of the NIH Human Immunology Project Consortium. This project in the lab is focused on systems immunology approaches for the study of human immune responses to Plasmodium falciparum infection and to anti-malaria vaccination. A complementary U01 project is focused on specific immune cell and immune receptor responses to malaria infection and vaccination and the influence of prior malaria infection. Insights gained from this research program have the potential for impacting strategies for vaccine development and for treating immune-related diseases more broadly.

RNA Editing

RNA editing is essential to the survival of the three major Trypanosomatid pathogens and does not occur in humans and is thus a source of targets for the development of drugs that are needed to treat infections by these parasites. Elucidating the details of the RNA editing process in the lab has also stimulated discoveries on different types of RNA editing of medical importance, including in humans. The lab determined the many aspects of the editing mechanism and molecular machinery that performs editing while showing 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 the proteins and multiprotein complexes that perform editing and are exploring the mysterious mechanisms that result in differential editing in different life cycle stages of the parasite which results in generation of cellular energy by different processes in different stages. Structure/function studies of the proteins and complexes that perform editing will aid the understanding of many nucleic acid processing mechanisms.

Cell Systems

The lab is using a wide variety of cell-wide systems biology approaches 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. It 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. The 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.

Antigenic Variation

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 discovered that a particular molecular regulatory system controls the selective expression of one of hundreds of surface proteins stage and antigenic switching via epigenetic processes that involves intracellular signaling and chromatin reorganization. It also showed that this regulatory system coordinately controls numerous cellular processes during cell development. The lab showed that the components of the system are conserved from Protozoa through humans and have expanded and diverged in the higher, probably to control the more complex processes in multicellular organisms.

 

Contact

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