A5024251843- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Computational Drug Discovery Methods
- 14-3-3 protein interactions
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Pelvic floor disorders treatments
- Protein Kinase Regulation and GTPase Signaling
- Glycosylation and Glycoproteins Research
- Advanced Statistical Methods and Models
- Cell Image Analysis Techniques
- S100 Proteins and Annexins
- HIV Research and Treatment
- Protein Degradation and Inhibitors
- Galectins and Cancer Biology
- Urinary Tract Infections Management
- Urinary Bladder and Prostate Research
- Virology and Viral Diseases
AstraZeneca (United Kingdom)
2024
University of Oxford
2017-2018
Ludwig-Maximilians-Universität München
2012-2014
Proteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism regulating intercellular signalling. TACE a major shedding protease, responsible for liberation inflammatory cytokine TNFα epidermal growth factor receptor. iRhoms, catalytically inactive members rhomboid-like superfamily, have been shown to control ER-to-Golgi transport maturation TACE. Here, we reveal that iRhom2 remains associated with throughout secretory pathway, stabilised at...
Abstract An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 one major sheddases involved a variety physiological and pathophysiological processes including regeneration, differentiation, cancer progression. This central role implies that ADAM17 activity has to be tightly regulated, at level localisation. Most mature localised intracellularly, with only small amount cell surface. We found...
Many intercellular signals are synthesised as transmembrane precursors that released by proteolytic cleavage ('shedding') from the cell surface. ADAM17, a membrane-tethered metalloprotease, is primary shedding enzyme responsible for release of inflammatory cytokine TNFα and several EGF receptor ligands. ADAM17 exists in complex with rhomboid-like iRhom proteins, which act cofactors regulate substrate shedding. Here we report poorly characterised FERM domain-containing protein FRMD8 new...
Signal peptide peptidase (SPP), its homologs, the SPP-like proteases SPPL2a/b/c and SPPL3, as well presenilin, catalytic subunit of γ-secretase complex, are intramembrane-cleaving aspartyl GxGD type. In this study, we identified 18-kDa leader (LP18) foamy virus envelope protein (FVenv) a new substrate for intramembrane proteolysis by human SPPL3 SPPL2a/b. contrast to SPPL2a/b γ-secretase, which require substrates with an ectodomain shorter than 60 amino acids efficient proteolysis, cleaves...
Hit screening, which involves the identification of compounds or targets capable modulating disease-relevant processes, is an important step in drug discovery. Some assays, such as image-based high-content screenings, produce complex multivariate readouts. To fully exploit richness data, advanced analytical methods that go beyond conventional univariate approaches should be employed. In this work, we tackle problem hit assays. As with a from assay can defined candidate yields value...
Abstract Many intercellular signals are synthesised as transmembrane precursors that released by proteolytic cleavage (‘shedding’) from the cell surface. ADAM17, a membrane-tethered metalloprotease, is primary shedding enzyme responsible for release of inflammatory cytokine TNFα and several EGF receptor ligands. ADAM17 exists in complex with rhomboid-like iRhom proteins, which act cofactors regulate substrate shedding. Here we report poorly characterised FERM domain-containing protein FRMD8...