- Trypanosoma species research and implications
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Peptidase Inhibition and Analysis
- Research on Leishmaniasis Studies
- Complementary and Alternative Medicine Studies
- Polyamine Metabolism and Applications
- Lysosomal Storage Disorders Research
- Malaria Research and Control
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Heavy Metals in Plants
- Cannabis and Cannabinoid Research
- Medicinal Plant Extracts Effects
- Synthesis of Tetrazole Derivatives
- Neonatal Health and Biochemistry
- Neurogenetic and Muscular Disorders Research
The University of Texas Southwestern Medical Center
2015-2022
The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines growth. Thymidine kinase (TK) catalyzes formation dTMP dUMP is one several enzymes that appear redundant to pathway. Surprisingly, we show through analysis TK conditional null RNAi cells essential growth infectivity in a mouse model, catalytically active enzyme required its function. Unlike humans,...
The causative agent of human African trypanosomiasis, Trypanosoma brucei, lacks de novo purine biosynthesis and depends on salvage from the host. pathway is redundant contains two routes to guanosine-5'-monophosphate (GMP) formation: conversion xanthosine-5'-monophosphate (XMP) by GMP synthase (GMPS) or direct guanine hypoxanthine-guanine phosphoribosyltransferase (HGPRT). We show recombinant T. brucei GMPS efficiently catalyzes formation. Genetic knockout in bloodstream parasites led...
The few frontline antileishmanial drugs are poorly effective and toxic. To search for new this neglected tropical disease, we tested the activity of compounds in Medicines Malaria Venture (MMV) "Pathogen Box" against Leishmania amazonensis axenic amastigotes. Screening yielded six discovery with EC50 values from 50 to 480 nM. Concentration–response assays demonstrated that best hit, MMV676477, had mid-nanomolar cytocidal potency intracellular amastigotes, Trypanosoma brucei, Plasmodium...
Dietary supplements derived from botanicals are commonly consumed and investigated in biomedical studies for their potential health benefits. Accurate identification quantification of key chemical constituents botanical ingredients is necessary consistent product preparations reproducible research results. Manufacturers need quantitative reference materials the interest to verify content products. The rigor reproducibility enhanced through thorough characterization interventions used...
Polyamines are essential for cell growth of eukaryotes including the etiologic agent human African trypanosomiasis (HAT), Trypanosoma brucei. In trypanosomatids, a key enzyme in polyamine biosynthetic pathway, S-adenosylmethionine decarboxylase (TbAdoMetDC) heterodimerizes with unique catalytically-dead paralog called prozyme to form active complex. higher eukaryotes, metabolism is subject tight feedback regulation by spermidine-dependent mechanisms that absent trypanosomatids. Instead, T....