- Trypanosoma species research and implications
- Carbohydrate Chemistry and Synthesis
- Research on Leishmaniasis Studies
- Glycosylation and Glycoproteins Research
- Lysosomal Storage Disorders Research
- Biochemical and Molecular Research
- Viral Infections and Immunology Research
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Studies on Chitinases and Chitosanases
- Viral gastroenteritis research and epidemiology
- Insect symbiosis and bacterial influences
- Enzyme Production and Characterization
- Galectins and Cancer Biology
- Cellular transport and secretion
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Parasites and Host Interactions
- Parasitic Infections and Diagnostics
- Viral Infectious Diseases and Gene Expression in Insects
- Hepatitis B Virus Studies
- Heat shock proteins research
- Complement system in diseases
- Virology and Viral Diseases
Harvard University
2023-2025
University of Dundee
2016-2025
Boston Children's Hospital
2020-2025
Wellcome Centre for Anti-Infectives Research
2017-2024
Boston Children's Museum
2020-2024
Brigham and Women's Hospital
2023-2024
Carilion Clinic
2019-2024
Virginia Tech
2019-2024
Circuit Therapeutics (United States)
2024
McGovern Institute for Brain Research
2022
Two forms of protein-membrane anchor have been described for the externally disposed glycoproteins eukaryotic plasma membranes; namely, hydrophobic transmembrane polypeptide and complex glycosylphosphatidylinositol (G-PI) moiety. The chemical structures major species G-PI anchors found on a single variant surface glycoprotein (VSG) parasitic protozoan Trypanosoma brucei were determined by combination nuclear magnetic resonance spectroscopy, mass spectrometry, modification, exoglycosidase...
The abbreviations used are: VSG, variant surface glycoprotein; mfVSG, membrane form of sVSG, soluble VSG sCtgp, sVSG COOH-terminal Pronase glycopeptide
Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and infantum, is one of major parasitic diseases worldwide. There an urgent need for new drugs to treat VL, because current therapies are unfit purpose in a resource-poor setting. Here, we describe development preclinical drug candidate, GSK3494245/DDD01305143/compound 8, with potential this neglected tropical disease. The compound series was discovered repurposing hits from screen against related parasite...
Summary The antigenic sites recognized by monoclonal antibodies with neutralizing activity for the Sabin vaccine strains of poliovirus serotypes 1, 2 and 3 have been studied isolation characterization mutants resistant to neutralization antibody. Three distinct identified which are designated site 3. Site 1 includes a region 12 amino acids VP1, from residues 89 100, corresponding VP1 has as an 2. This was strongly immunodominant in type but not detected 1. is complex including 220 222 (site...
The CD52 antigen was extracted from human spleens with organic solvents and purified by immunoaffinity reverse-phase chromatography. latter step resolved two species, called CD52-I CD52-II. Both species were found to contain similar N-linked oligosaccharides glycosylphosphatidylinositol (GPI) anchor glycans. characterized methylation linkage analysis and, following exhaustive neuraminidase endo-β-galactosidase digestion, the reagent array method+. results showed that single N-glycosylation...
The membrane form of Trypanosoma brucei variant surface glycoprotein (mfVSG) is acylated with ester-linked tetradecanoic (myristic) acid (Ferguson, M. A. J., and Cross, G. (1984) J. Biol. Chem. 259, 3011-3015). Comparative analysis Pronase peptides from mfVSG soluble VSG localizes the site acylation to a COOH-terminal oligosaccharide structure. Chemical enzymatic treatment fragment revealed that myristic present as diglyceride (sn-1,2-dimyristin) probably linked via phosphodiester bond...
The variant surface glycoproteins (VSGs) of Trypanosoma brucei are synthesized with a hydrophobic COOH-terminal peptide that is cleaved and replaced by glycophospholipid, which anchors VSG to the membrane.The kinetics processing were studied metabolic labeling [36S]methionine r3H]myristic acid.The oligosaccharide-containing structure remaining after phospholipase removal dimyristyl glycerol from membrane-form could be detected serologically within 1 min polypeptide synthesis in two T. brueei...
The outer layer of the Candida albicans cell wall is enriched in highly glycosylated mannoproteins that are immediate point contact with host and strongly influence host-fungal interaction. N-Glycans major form mannoprotein modification consist a core structure, common to all eukaryotes, further elaborated Golgi branched chain characteristic fungi. In yeasts, branching initiated by action alpha1,6-mannosyltransferase Och1p; therefore, we disrupted C. OCH1 homolog determine importance...
Sera of patients with chronic Chagas' disease (American trypanosomiasis) contain elevated levels anti-alpha-galactosyl antibodies that are lytic to Trypanosoma cruzi. The T. cruzi trypomastigote F2/3 antigen complex recognized by these runs as a broad smear on SDS/PAGE [Almeida, Krautz, Krettli and Travassos (1993) J. Clin. Lab. Anal. 7, 307-316]. Treatment cells bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) abolished most their reactivity Chagas'-disease ((Chagasic, Ch)...
The major cell surface glycoconjugate of the parasitic protozoan Leishmania is a heterogeneous lipophosphoglycan. It has tripartite structure, consisting phosphoglycan (Mr 5,000-40,000), variably phosphorylated hexasaccharide glycan core, and lysoalkylphosphatidylinositol (lysoalkyl-PI) lipid anchor. structures core were determined by monosaccharide analysis, methylation fast atom bombardment-mass spectrometry, one- two-dimensional 500-MHz (correlated spectroscopy (COSY), homonuclear...
CAMPATH-1 antibodies recognize a unique molecule on human lymphocytes and are unusually efficient at causing cell lysis with homologous complement. They have been successfully used for lymphocyte depletion in vivo variety of diseases. We find that the antigen is very small glycosylphosphatidylinositol (GPI)-anchored glycoprotein mature peptide comprising only 12 amino acids. It can be separated into two distinct antigenic fractions which differ their susceptibility to...
A 4 month old child was immunized with a vaccine containing the Sabin live attenuated strains of all three serotypes poliovirus. The antigenic and molecular evolution strain poliovirus type 3 then followed throughout entire period virus excretion. Novel appeared at 8, 42 52 days post-vaccination were products both intertypic recombination between 2 in regions genome coding for non-structural proteins point mutations region structural proteins. Excretion continued 73 days. All examined...
Abstract Components of Trypanosoma cruzi able to induce the production IL-12 and other proinflammatory cytokines by macrophages were identified. Murine inflammatory cultured with live parasites or cellular components from different developmental forms T. (i.e., trypomastigotes, amastigotes, metacyclic epimastigotes), cytokine levels measured after 24 48 h. Our results indicate that trypomastigotes amastigotes (but not epimastigotes trypomastigotes) as well trypomastigote extracts derived...