- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Tissue Engineering and Regenerative Medicine
- HIV/AIDS drug development and treatment
- Galectins and Cancer Biology
- vaccines and immunoinformatics approaches
- Immune responses and vaccinations
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Proteoglycans and glycosaminoglycans research
- Neuropeptides and Animal Physiology
- Cytomegalovirus and herpesvirus research
- Chemokine receptors and signaling
- Hypothalamic control of reproductive hormones
- Cytokine Signaling Pathways and Interactions
- Dialysis and Renal Disease Management
- CAR-T cell therapy research
- Antimicrobial Peptides and Activities
- Muscle and Compartmental Disorders
St George's, University of London
2010-2022
AgriBio
2021
University of Pennsylvania
2018-2020
University of Cape Town
2013-2018
Innovative BioTherapies (United States)
2006-2016
Queen Mary University of London
2005
Howard Hughes Medical Institute
1994-2003
University of Michigan
1994-2003
May Institute
1995
University of Chicago
1995
Some cancer patients are immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, increasing evidence suggests chemotherapy drugs may stimulate beneficial changes in both the immune system tumour.We have assessed expression of human leucocyte antigen class 1 (HLA1) on tumour cells before after agents (cyclophosphamide, oxaliplatin or gemcitabine). In addition, we show chemotherapy-stressed release cytokines enhance...
Certain of the glycoprotein hormones, including bovine lutropin (bLH), bear asparagine-linked oligosaccharides terminating with sequence SO4-4GalNAc beta 1-4GlcNAc 1-2Man alpha. To establish biologic significance these sulfate-bearing we have compared properties native bLH, desulfated recombinant bLH produced in Chinese hamster ovary cells that bears sialic acid alpha 2- 3Gal rather than sulfated (bLH/CHO), and desialyzed bLH/CHO. Using cultured MA-10 cells, a Leydig cell tumor line...
Glycoprotein fucosylation enables fringe-dependent modulation of signal transduction by Notch transmembrane receptors, contributes to selectin-dependent leukocyte trafficking, and is faulty in adhesion deficiency (LAD) type II, also known as congenital disorder glycosylation (CDG)-IIc, a rare human characterized psychomotor defects, developmental abnormalities, defects. We report here that mice with an induced null mutation the FX locus, which encodes enzyme de novo pathway for GDP–fucose...
Costimulation mediated by the CD28 receptor has been shown to play an important role in development of a vigorous T cell immune response. Nevertheless, CD28-deficient mice can mount effective cell-dependent responses. These data suggest that other costimulatory molecules may activation. In search for receptors on cells, we have characterized monoclonal antibody (mAb) costimulate cells absence accessory cells. Similar antibodies, this mAb, R2/60, was found synergize with engagement inducing...
Lutropin (LH) bears asparagine-linked oligosaccharides terminating with the unique sequence SO4-4GalNAc beta 1-4GlcNAc 1-2Man alpha, whereas follitropin (FSH) predominantly Sia alpha-Gal where is sialic acid. We previously identified a glycoprotein-hormone-specific N-acetylgalactosamine-transferase (GalNAc-transferase) that recognizes peptide-recognition marker(s) present on common glycoprotein hormone alpha subunit and subunits of human chorionic gonadotropin LH but not FSH. have now an...
The glycoprotein hormones lutropin (LH) and follitropin (FSH), which have common α-subunits but hormone-specific β-subunits, are both synthesized in the gonadotroph. However, they bear Asn-linked oligosaccharides that differ structure. Those on LH terminate with sequence SO 4 -4GalNAcβ1→4GlcNAcβ1→2Manα, whereas those FSH sialic acidα-Galβ1→4GlcNAcβ1→2Manα. A GalNAc-transferase was identified bovine pituitary membranes recognizes features of α-subunit peptide adds GalNAc to its an apparent...
There is a strong epidemiological link between smoking and tuberculosis (TB), but the association confounded by socioeconomic other factors. A direct relationship cigarette smoke poor treatment-related outcomes in patients with TB therefore questionable. We investigated whether constituents of tobacco impair mycobacterial host immune responses vitro.
To determine how the α(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, selectin ligands they control may contribute to adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient either or both enzymes. We find a substantial CHS deficiency Fuc-TVII−/− mice, complete Fuc-TIV−/−/Fuc-TVII−/− mice. These defects are not accounted for by alterations number function of epidermal Langerhans cells required cutaneous antigen processing presentation. By contrast,...
Two monoclonal antibodies termed CT1 and CT2 define a cell surface oligosaccharide molecule expressed on restricted populations of murine lymphocytes. This structure is largely associated with the extracellular domain CD45 family tyrosine phosphatases, molecules required for lymphocytes to proliferate in response antigen stimulation. Previous work has shown that recognized by CT identical, at least part, human Sda blood group, formed through enzymatic addition N-acetylgalactosamine beta...
The Asn-linked oligosaccharides from bovine lutropin (bLH(Pit] are predominantly dibranched complex-type structures with the terminal sequence SO4-4GalNAc beta 1,4GlcNAc 1,2Man alpha. Recombinant bLH expressed in Chinese hamster ovary cells (bLH(CHO] bears di- (60%) and tribranched (30%) oligosaccharides; however, these terminate Sia alpha 2,3Gal In contrast to limited spectrum of oligosaccharide present on recombinant bLH(CHO), endogenous glycoproteins synthesized by CHO bear a...
Subsets of mammalian cell surface oligosaccharides contain specific fucosylated moieties expressed in lineage- and/or temporal-specific patterns. The functional significance these structures is incompletely defined, although there evidence that subsets them, represented by the sialyl Lex determinant, are important participants leukocyte adhesion and trafficking processes. Genetic deletion mouse has been a powerful tool to address questions about glycans. However, successful use such...
Abstract T lymphocytes up-regulate the synthesis of ligands for E- and P-selectin during proliferative responses in vivo vitro. Previous studies from our laboratories indicated that α(1,3)-fucosyltransferase FucT-VII regulates E-selectin sialylated Lewisx-related epitopes (sLex-related epitopes) human lymphoblasts. The current report shows production both P- is dependent, but peak each occurs at different levels fucosyltransferase activity intact cells. In brief, mRNA were higher cultured...
Summary Dendritic cells produce cytokines that regulate the class of adaptive immune response. Microbial recognition is mediated, at least in part, by pattern receptors such as Toll‐like receptors, which influence dendritic cell maturation. In humans it not yet clear how intact pathogens modulate developing To address effects on maturation and effector functions human cells, we investigated their responses to a number microbial pathogens. We studied range micro‐organisms including...
Cell therapy for the treatment of renal failure in acute setting has proved successful, with therapeutic impact, yet development a sustainable, portable bioartificial kidney chronic to be realized. Challenges maintaining an anticoagulated blood circuit, typical platform solute clearance and support biological components, have posed major hurdle advancement this technology. This group developed Bioartificial Renal Epithelial System (BRECS) capable differentiated cell function while sustained...
Some members of the glycoprotein hormone family [luteinizing (LH), thyroid-stimulating (TSH), and free alpha subunit] bear unique asparagine-linked oligosaccharides with terminal sequence SO4-Gal-NAc beta 1,4GlcNAc 1,2Man alpha, whereas other [human chorionic gonadotropin (hCG) follicle-stimulating (FSH)] predominantly terminating in sialic acid alpha-Gal alpha. We previously identified an N-acetylgalactosaminetransferase (GalNAc-transferase) bovine pituitary membranes that specifically...
The Sda blood group carbohydrate structure, GaINAcβl-4[NeuAcα2–3]Galβl-4GlcNAc-R, is expressed on glycolipid and glycoprotein in human gastrointestinal mucosa. expression of the determinant dramatically decreases cancer tissue. activity βl,4N-acetylgalactosaminyltransferase (Sda-GaINAcT), which transfers GaINAc to NeuAcα2–3Galβl-4Glc(NAc)-R, correlates with immuno-epitope. From total RNA fraction gastric mucosa, we have amplified a cDNA segment by reverse-transcription-polymerase-chain...
Abstract The cell adhesion molecules (CAMs) required for T lymphocyte recruitment during pulmonary immune responses have not been defined. Our laboratories recently reported that intratracheal (IT) challenge of sensitized mice with SRBC induced prolonged expression vascular P-selectin, E-selectin, and VCAM-1, particularly in areas mononuclear leukocyte infiltration. A surge the number circulating lymphocytes expressing selectin ligands preceded peak accumulation cells lung. In addition, a...
Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through amelioration cardiac and vascular dysfunction. Safety ability RAD to improve clinical outcomes was demonstrated a Phase II trial, which patients had high prevalence sepsis. Even with these promising results, delivery is hampered by manufacturing hurdles, including sourcing, large-scale manufacture, storage delivery. To address limitations,...