A5057077914- Monoclonal and Polyclonal Antibodies Research
- TGF-β signaling in diseases
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Pediatric Hepatobiliary Diseases and Treatments
- Protein Tyrosine Phosphatases
- Genetics and Neurodevelopmental Disorders
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Developmental Biology and Gene Regulation
- CAR-T cell therapy research
- Neurotransmitter Receptor Influence on Behavior
- Systemic Sclerosis and Related Diseases
- Skin and Cellular Biology Research
- Protease and Inhibitor Mechanisms
- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Wnt/β-catenin signaling in development and cancer
- Neonatal Health and Biochemistry
- Connective tissue disorders research
- Force Microscopy Techniques and Applications
- Marine Sponges and Natural Products
- Signaling Pathways in Disease
Immunocore (United Kingdom)
2021-2023
Immunocore (United States)
2022
University of Oxford
2009-2019
John Radcliffe Hospital
2009-2010
Max Planck Institute of Biophysics
2007
Stiff skin syndrome, an autosomal dominant congenital form of scleroderma, is caused by mutations in the domain fibrillin-1 that mediates integrin binding.
Significance The Notch pathway is a crucial metazoan cell–cell signaling pathway. receptor regulated by O -glycosylation, sugar modification that involves series of enzyme-catalyzed additions to residues within EGF domains. Here, we demonstrate the Fringe enzyme enhances affinity fragment for its ligand. X-ray crystallographic analysis demonstrates backbone structure does not change as consequence modification, suggesting addition directly ligand binding, although indirect effects cannot be...
Neoantigens derived from somatic mutations are specific to cancer cells and ideal targets for immunotherapy. KRAS is the most frequently mutated oncogene drives pathogenesis of several cancers. Here we show identification development an affinity-enhanced T cell receptor (TCR) that recognizes a peptide common mutant,
The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles cell-fate determination, stem cell maintenance, immune activation, and angiogenesis. Signals are initiated by extracellular interactions of the receptor Delta/Serrate/Lag-2 (DSL) ligands, whose structure highly conserved throughout evolution. To date, no or activity has been associated extreme N termini even though numerous mutations this region Jagged-1 ligand lead to human disease. Here, we...
Abstract Recent data have expanded our understanding of Notch signalling by identifying a C2 domain at the N‐terminus ligands, which has both lipid‐ and receptor‐binding properties. We present novel structures human ligands Jagged2 Delta‐like4 Notch2, together with functional assays, suggest that ligand‐mediated coupling membrane recognition binding is likely to be critical in establishing optimal context for signalling. Comparisons between Jagged Delta family show huge diversity loops apex...
Abstract The role of Notch signaling and its ligand JAGGED1 (JAG1) in tumor biology has been firmly established, making them appealing therapeutic targets for cancer treatment. Here, we report the development characterization human/rat-specific JAG1-neutralizing mAbs. Epitope mapping identified their binding to receptor interaction site within JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective murine Jag1 ortholog. These antibodies were able specifically inhibit...
MINT‐7905703: Vn (uniprotkb:P04004) and bind (MI:0407) by molecular sieving (MI:0071)
Integrin α5β1 binds the human 9th–10th type III fibronectin domain pair (FIII9–10) to mediate cell attachment and spreading. FIII9–10 mutants with increased conformational stability (FIII9′10) or highly restricted interdomain mobility (FIII9′10-CC) support spreading greater lesser extents, respectively. We have used neutron reflectivity show that surface adsorbed layers of wild-type mutant proteins are remarkably different. At bulk concentrations protein equivalent those in assays, coverage...
We have investigated the existence of a precoupled form distal C‐terminal truncated cannabinoid receptor 1 (CB1‐417) and heterotrimeric G proteins in heterologous insect cell expression system. CB1‐417 showed higher production levels than full‐length receptor. The obtained our system were double values reported literature. also observed that at least C‐terminus was not involved dimerization, as predicted Using fluorescence resonance energy transfer, we found Gα i1 β γ 2 colocalized cells....
Abstract: Recent data have expanded our understanding of Notch signaling by identifying a C2 domain at the N-terminus ligands which has both lipid- and receptor-binding properties. We present novel structures human Jagged2 DLL4 Notch-2, together with functional assays, suggest that ligand-mediated coupling membrane recognition binding is likely to be critical in establishing optimal context for signaling. Comparisons between Jagged Delta family show huge diversity loops apex implicated...
<h3>Background</h3> KRAS is the most frequently mutated oncogene, yet mutant has historically been a challenging target for conventional small molecule drug development. Tumour specific neoantigen peptides derived from are presented by cell surface human leucocyte antigens (HLA) and form class of shared, tumour-specific that attractive targets immunotherapy. <h3>Methods</h3> A T clone specifically recognizes common G12D as peptide in context HLA-A*11:01 was isolated healthy donor PBMCs. The...
<p>1: JAG1 antibody characterization. 2: inhibition of mediated Notch signalling in tumor cell lines. 3: vascular cells. 4: HUVEC-HUVSMC co-culture. 5: effect anti-Notch pathway treatment on MDA-MB231 2D growth and J1-65D titration 3D gene expression. 6: established OVCAR3 xenograft. 7: antibodies cross-reactivity with rat Jag1. 8: anti-JAG1 a brain metastasis model.</p>
<p>Supplementary material and methods. Supplementary table 1: cell lines growth conditions. 2: Notch ligands control protein for plate coating. 3: qPCR primers. 4: flow cytometry antibodies. 5: ICC/IHC 6: titration of Notch1-JAG1 binding inhibition by JAG1 7: amino acid sequence 8: blood analysis on antibody-treated tumor-bearing rats.</p>
<p>Supplementary material and methods. Supplementary table 1: cell lines growth conditions. 2: Notch ligands control protein for plate coating. 3: qPCR primers. 4: flow cytometry antibodies. 5: ICC/IHC 6: titration of Notch1-JAG1 binding inhibition by JAG1 7: amino acid sequence 8: blood analysis on antibody-treated tumor-bearing rats.</p>
<p>1: JAG1 antibody characterization. 2: inhibition of mediated Notch signalling in tumor cell lines. 3: vascular cells. 4: HUVEC-HUVSMC co-culture. 5: effect anti-Notch pathway treatment on MDA-MB231 2D growth and J1-65D titration 3D gene expression. 6: established OVCAR3 xenograft. 7: antibodies cross-reactivity with rat Jag1. 8: anti-JAG1 a brain metastasis model.</p>
<div>Abstract<p>The role of Notch signaling and its ligand JAGGED1 (JAG1) in tumor biology has been firmly established, making them appealing therapeutic targets for cancer treatment. Here, we report the development characterization human/rat-specific JAG1-neutralizing mAbs. Epitope mapping identified their binding to receptor interaction site within JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective murine Jag1 ortholog. These antibodies were able...
<div>Abstract<p>The role of Notch signaling and its ligand JAGGED1 (JAG1) in tumor biology has been firmly established, making them appealing therapeutic targets for cancer treatment. Here, we report the development characterization human/rat-specific JAG1-neutralizing mAbs. Epitope mapping identified their binding to receptor interaction site within JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective murine Jag1 ortholog. These antibodies were able...
Abstract KRAS is the most frequently mutated oncogene. Tumour specific neoantigen peptides derived from are presented by cell surface human leucocyte antigens (HLA) and form a class of shared, public tumour-specific for T receptors (TCR) that attractive targets immunotherapy. We have previously reported engineering soluble engaging ImmTAC (Immune mobilising monoclonal TCR Against Cancer) molecule, IMC-KRASG12D KRASG12D peptide HLA-A*11:01. was extensively characterised demonstrated potent...