Research Interests:
Research Interests:
Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium , affects over 112 million people worldwide. As with S. mansoni infections, the pathology in urogenital schistosomiasis is mainly related to the egg... more
Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium , affects over 112 million people worldwide. As with S. mansoni infections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoni organism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible role in immune modulation of host cell tissues. Whether IPSE homologs are expressed in other Schistosome species has not been investigated. Here, we describe the cloning of two paralog genes H03-IPSE and H06-IPSE which are the ortholog of M-IPSE, from the egg-cDNA of S. haematobium . Using PCR and...
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Research Interests: Brazil, Adolescent, Biological Sciences, Humans, Child, and 15 moreFemale, Animals, Male, Young Adult, Glycoproteins, Aged, Middle Aged, Adult, Feces, Schistosoma Mansoni, Sensitivity and Specificity, Enzyme Linked Immunosorbent Assay, Case Control Studies, Immunochromatography, and Medical and Health Sciences
Schistosoma mansoni parasites reside in the circulatory sys- tem of their human host where they can survive for up to 30 years. In this aerobic environment, worms must have effec- tive mechanisms to maintain cellular redox balance,... more
Schistosoma mansoni parasites reside in the circulatory sys- tem of their human host where they can survive for up to 30 years. In this aerobic environment, worms must have effec- tive mechanisms to maintain cellular redox balance, including immune-generated oxygen radicals as well as those generated in the parasite during respiration and the breakdown and con- sumption of host hemoglobin.
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ABSTRACT
Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a... more
Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory activity against the protozoan parasite Trypanosoma brucei (lobosamide A IC50 = 0.8 μM), the causative agent of human African trypanosomiasis (HAT). The biosynthetic gene cluster of the lobosamides was sequenced and suggests a conserved cluster organization among the 26-membered macrolactams. While determination of the relative and absolute configurations of many members of this family is lacking, the absolute configurations of the lobosamides were deduced using a combination of chemical modification, detailed spectroscopic analysis, and bioinformatics. We implemented a "molecules-to-genes-to-molecules" approach to determine the ...
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The pressing need for better drugs against Chagas disease, African sleeping sickness and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain and SmCB1, the major cysteine proteases from Trypanosoma cruzi, Trypanosoma... more
The pressing need for better drugs against Chagas disease, African sleeping sickness and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain and SmCB1, the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei and Schistosoma mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain and 5 SmCB1 inhibitors with IC50 ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside ( 4I: ) was discovered as a potent rhodesain inhibitor (IC50= 1.2 ± 1.0 μM). The impact of a range of modifications was determined: removal of thiosemicarbazone or its replacement by semicar...
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Research Interests: Mass Spectrometry, Gene expression, Biological Sciences, Copper, Animals, and 15 moreDrug Resistance, Heavy Metal, Glutathione, Alternative splicing, Iron, Cadmium, Enzyme activity, Alternative Splicing, Anthelmintics, Open Reading Frame, Drug Targeting, Gene Expression Regulation, Gene expression profiling, Cysteine Protease, and Medical and Health Sciences
... David L. Williamsa,∗ , Ahmed A. Sayeda, Debalina Raya, Andrew G. McArthurb ... Comput Appl Biosci 1992;8: 27582. [13] Fuhrmann M, Hausherr A, Ferbitz L, Schödl T, Heitzer M, Hegemann P. Monitoring dynamic expression of nuclear genes... more
... David L. Williamsa,∗ , Ahmed A. Sayeda, Debalina Raya, Andrew G. McArthurb ... Comput Appl Biosci 1992;8: 27582. [13] Fuhrmann M, Hausherr A, Ferbitz L, Schödl T, Heitzer M, Hegemann P. Monitoring dynamic expression of nuclear genes in Chlamydomonas ...
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A sequence database was created for theLeishmania N-acetylglucosamine-1-phosphate transferase (nagt) gene from 193 independent isolates. PCR products of this single-copy gene were analyzed for restriction fragment length polymorphism... more
A sequence database was created for theLeishmania N-acetylglucosamine-1-phosphate transferase (nagt) gene from 193 independent isolates. PCR products of this single-copy gene were analyzed for restriction fragment length polymorphism based on sevennagtsequences initially available. We subsequently sequenced 77 samples and found 19 new variants (genotypes). Alignment of all 26nagtsequences is gap free, except for a single codon addition or deletion. Phylogenetic analyses of the sequences allow grouping the isolates into three subgenera, each consisting of recognized species complexes, i.e., subgenusLeishmania(L. amazonensis-L. mexicana,L. donovani-L. infantum,L. tropica,L. major, andL. turanica-L. gerbilli), subgenusViannia(L. braziliensis,L. panamensis), and one unclassified (L. enriettii) species. This hierarchy of grouping is also supported by sequence analyses of selected samples for additional single-copy genes present on different chromosomes. Intraspecies divergence ofnagtvari...
Research Interests: Genetics, Membrane Proteins, Leishmania, Biological Sciences, Phylogeny, and 12 moreAnimals, Polymerase Chain Reaction, Endoplasmic Reticulum, Rare Event, Genome, Single Cell, Amino Acid Sequence, In Silico, Eukaryotic Cell, Molecular Sequence Data, Selective Sampling, and Medical and Health Sciences
Leishmania amazonensis, a causative agent of cutaneous leishmaniasis, is susceptible in vitro to light-mediated cytolysis in the presence of or after pretreatment with the photosensitizer aluminum phthalocyanine chloride. Cytolysis of... more
Leishmania amazonensis, a causative agent of cutaneous leishmaniasis, is susceptible in vitro to light-mediated cytolysis in the presence of or after pretreatment with the photosensitizer aluminum phthalocyanine chloride. Cytolysis of both promastigotes and axenic amastigotes required less photosensitizer (e.g., one μg · ml−1) and a lower light dose (e.g., 1.5 J · cm−2) than did the mammalian cells examined for comparison. Exposure of Leishmania cells to the photosensitizer alone had little effect on their viability, as judged from their motility, growth, and/or retention of green fluorescent proteins genetically engineered for episomal expression. Fluorimetric assays for cell-associated and released green fluorescence proteins proved to be even more sensitive for the evaluation of cell viability than microscopy for the evaluation of motility and/or integrity. Axenic amastigotes pretreated with the photosensitizer infected macrophages of the J774 line but were lysed intracellularly ...
Research Interests: Microbiology, Clinical Trial, Medical Microbiology, Photodynamic Therapy, Genetic Engineering, and 14 moreMice, Animals, Drug Resistance, Antimicrobial activity, Cell Viability, Green Fluorescent Protein, Photochemotherapy, Antimicrobial agents, Skin Disease, Cutaneous Leishmaniasis, Photolysis, Organometallic Compounds, Cell Membrane, and Pharmacology and pharmaceutical sciences
Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the... more
Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first- ...