A5035474970- Trypanosoma species research and implications
- Calcium signaling and nucleotide metabolism
- Research on Leishmaniasis Studies
- Biotin and Related Studies
- Helminth infection and control
- Toxoplasma gondii Research Studies
- Lysosomal Storage Disorders Research
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Malaria Research and Control
- Polyamine Metabolism and Applications
- Parasitic Infections and Diagnostics
Harvard University
2021-2023
University of Nebraska at Omaha
2020
We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 MMV084978) selects for mutations in PfAcAS. Metabolic profiling compound-treated parasites reveals changes acetyl-CoA levels both compounds. Genome editing confirms that PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate is essential asexual...
The flagellated kinetoplastid protozoan and causative agent of human Chagas disease, Trypanosoma cruzi, inhabits both invertebrate mammalian hosts over the course its complex life cycle. In these disparate environments, T. cruzi uses single flagellum to propel motile stages and, in some instances, establish intimate contact with host. Beyond role motility, functional capabilities have not been defined. Moreover, lack proteomic information for this organelle, any parasite stage, has limited...
Throughout its complex life cycle, the uniflagellate parasitic protist, Trypanosoma cruzi, adapts to different host environments by transitioning between elongated motile extracellular stages and a nonmotile intracellular amastigote stage that replicates in cytoplasm of mammalian cells. Intracellular T. cruzi amastigotes retain short flagellum extends beyond opening flagellar pocket with access milieu. Contrary long-held view is inert, we report this organelle displays quasiperiodic beating...
In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani, CYP51 essential, yet in major, cognate dispensable for growth; but not heat resistance. The essentiality specific role ergostane-type sterol...
Abstract The flagellated kinetoplastid protozoan and causative agent of human Chagas disease, Trypanosoma cruzi , inhabits both invertebrate mammalian hosts over the course its complex life cycle. In these disparate environments, T. uses single flagellum to propel motile stages in some instances, establish intimate contact with host. Beyond role motility, functional capabilities have not been defined. Moreover, lack proteomic information for this organelle, any parasite stage, has limited...
Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating need for enhanced therapies. KG8 benzoquinone acyl hydrazone chemotype identified from previous chemical screen which we previously showed vitro vivo efficacy against T. However, genetic target mechanism action remain unknown. To investigate potential targets,...
Abstract In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani , CYP51 essential, yet in major cognate dispensable for growth; but not heat resistance. The essentiality specific role...
Abstract Throughout its complex life cycle, the uniflagellate parasitic protist, Trypanosoma cruzi , adapts to different host environments by transitioning between elongated motile extracellular forms and non-motile intracellular amastigote that replicate in cytoplasm of mammalian cells. Despite their name, T. amastigotes retain a short flagellum extends beyond opening flagellar pocket with access milieu. Contrary long-held view is inert, we now report this organelle displays quasiperiodic...