A5055148836- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Regulation of Appetite and Obesity
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Virus-based gene therapy research
- Biotin and Related Studies
- Biochemical Analysis and Sensing Techniques
- Receptor Mechanisms and Signaling
- Cholesterol and Lipid Metabolism
- Bioinformatics and Genomic Networks
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Multiple Myeloma Research and Treatments
- Asthma and respiratory diseases
VIB-UGent Center for Medical Biotechnology
2008-2025
Ghent University
2008-2024
Vlaams Instituut voor Biotechnologie
1998-2014
Roche (Belgium)
1992-1995
Roche (Switzerland)
1993
The leptin system provides a link between adipose mass and the central nervous system. appetite suppressing effects of are impaired in most obese patients some mutant mice strains. Herein we describe how suppressor cytokine signalling 3 (SOCS3), potential mediator this resistance is recruited into activated murine receptor complex. Using functional assay based on inhibition mediated reporter induction, using phosphopeptide affinity chromatography show binding SOCS3 to highly conserved...
By use of a 3' extension PCR strategy, cDNA clones were isolated spanning the transmembrane region and complete cytoplasmic domain human interleukin 5 receptor alpha subunit (hIL5R alpha). These cDNAs differ from previously encoding soluble hIL5R form by sequence switch at position 1243. When expressed in COS-1 cells, only low-affinity binding 125I-labeled was observed. Coexpression beta chain led to 2-fold increase affinity. In addition, this same cloning strategy allowed us identify...
The leptin/leptin receptor system shows strong similarities to the long-chain cytokine interleukin-6 (IL-6) and granulocyte colony-stimulating factor cytokine/receptor systems. IL-6 family cytokines interact with their receptors through three different binding sites I-III. leptin structure was superposed on crystal structures of several cytokines, a series mutants generated focusing effect mutations (LR) signaling membrane proximal homology domain (CRH2) LR determined. Mutations in site I at...
An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy and remain active in case of recurrence. Furthermore, it preferably not rely on tumor-specific surface markers, as these are only available a limited set malignancies. Despite approval for treatment various cancers, clinical application cytokines is still impeded by their multiple toxic side effects. Type I IFN has long history cancer, but its multifaceted activity pattern...
A detailed structure-function analysis of human interleukin 5 (hIL5) has been performed. The hIL5 receptor is composed two different polypeptide chains, the alpha and beta subunits. subunit alone sufficient for ligand binding, but association with leads to a 2- 3-fold increase in binding affinity. chain shared receptors IL3 granulocyte/macrophage-colony-stimulating factor--hence descriptor C (C common). All mutants were analyzed solid-phase assay hIL5R interaction proliferation using...
Recombinant soluble human interleukin-5 receptor alpha (shIL-5R alpha) has been expressed in COS-1 cells and baculovirus-infected cells. The protein was purified from the supernatant by chromatography on concanavalin A-Sepharose, MonoQ, a final gel filtration step. A chimeric fusion (hIL-5R alpha-h gamma 3) constructed of cDNA corresponding to shIL-5R Fc part IgG C 3 chain, insect secreted as disulfide-linked homodimer, G affinity chromatography. In solid-phase binding assay bivalent hIL-5R...
Despite approval for the treatment of various malignancies, clinical application cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal activity upon cell-specific impact. We here show that IFN-derived AcTaferon targeted to tumor displays strong antitumor without any associated toxicity, contrast with wild IFN. Treatment CD20-targeted CD20+...
Abstract Cell lysis is an inevitable step in classical mass spectrometry–based strategies to analyse protein complexes. Complementary conditions, situ cross-linking and proximal labelling techniques are currently used reduce effects on the complex. We have developed Virotrap, a viral particle sorting approach that obviates need for cell homogenization preserves complexes during purification. By fusing bait HIV-1 GAG protein, we show interaction partners become trapped within virus-like...
Abstract The enzyme cholesterol lecithin acyl transferase (LCAT) shares the Ser/Asp‐Glu/His triad with lipases, esterases and proteases, but low level of sequence homology between LCAT these enzymes did not allow for fold to be identified yet. We, therefore, relied upon structural calculations using threading methods based on alignment against a library solved three‐dimensional protein structures, prediction fold. We propose that LCAT, like belongs α/β hydrolase family, central domain...
Article8 January 2020Open Access Source DataTransparent process Safe eradication of large established tumors using neovasculature-targeted tumor necrosis factor-based therapies Leander Huyghe Cytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department Biomolecular Medicine, Ghent University, Ghent, Belgium Search more papers by this author Alexander Van Parys BelgiumShared authorship Anje Cauwels Sandra Lint Stijn De Munter Clinical Chemistry, Microbiology and Immunology,...
Exogenous glucocorticoids are frequently used to treat inflammatory disorders and as adjuncts for the treatment of solid cancers. However, their use is associated with severe side effects therapy resistance. Novel glucocorticoid receptor (GR) ligands a patient-validated reduced effect profile have not yet reached clinic. GR member nuclear family transcription factors heavily relies on interactions coregulator proteins its transcriptional activity. To elucidate role interactome in...
Protein-protein interactions play an important biological role in every aspect of cellular homeostasis and functioning. Proximity labeling mass spectrometry-based proteomics overcomes challenges typically associated with other methods has quickly become the current state art field. Nevertheless, tight control proximity-labeling enzymatic activity expression levels is crucial to accurately identify protein interactors. Here, we leverage a T2A self-cleaving peptide non-cleaving mutant...
In a previous characterization of the ABCA subfamily ATP-binding cassette (ABC) transporters, we identified potential protein kinase 2 (CK2) phosphorylation sites, which are conserved in eukaryotic and prokaryotic members transporters (Peelman, F., Labeur, C., Vanloo, B., Roosbeek, S., Devaud, Duverger, N., Denefle, P., Rosier, M., Vandekerckhove, J., Rosseneu, M. (2003) J. Mol. Biol. 325, 259-274). These residues located cytoplamic R1 R2 domains, downstream nucleotide binding domains NBD1...
The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such reproduction and immune responses. Accumulating evidence suggests that plays role in human pathologies, autoimmune diseases cancer, thus providing rationale for development of antagonists. In present study, we generated evaluated panel neutralizing nanobodies targeting LR (leptin receptor). A nanobody comprises variable domain naturally occurring...
Recent approval of chimeric antigen receptor (CAR) T cell therapy by the European Medicines Agency (EMA)/Federal and Drug Administration (FDA) remarkable results CAR clinical trials illustrate curative potential this therapy. While CARs against a multitude different antigens are being developed tested (pre)clinically, there is still need for optimization. The use single-chain variable fragments (scFvs) as targeting moieties hampers quick generation functional could potentially limit...
Glucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit bone marrow microenvironment to obtain growth and survival signals, resistance glucocorticoid-induced apoptosis emerges, yet underlying mechanisms remain poorly characterized. Here, we identify that chemokine receptor CCR1, together with its main ligand CCL3, plays a pivotal role reducing glucocorticoid sensitivity cells. We show blocking CCR1 signaling antagonist BX471 enhances...
Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation the leptin receptor. On basis kinetic studies, two distinct gene sets could be discerned: signal transducer and activator transciption-3 (STAT-3), suppressor cytokine signalling-3 (SOCS-3), MT-II (metallothionein-II), serine/threonine kinase fibroblast-growth-factor-inducible (Fnk) modulator recognition factor (MRF-1), which are immediate early response genes,...
Binding of GH to its receptor induces rapid phosphorylation conserved tyrosine motifs that function as recruitment sites for downstream signaling molecules. Using mammalian protein-protein interaction trap (MAPPIT), a two-hybrid method, we mapped the binding in signal transducer and activator transcription 5 (STAT5) b negative regulators cytokine cytokine-inducible Src-homology 2 (SH2)-containing protein (CIS) suppressor (SOCS2). Y534, Y566, Y627 are major STAT5. A non-overlapping pattern is...
The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such reproduction and immune responses. We here provide genetic biochemical evidence that functions of can be uncoupled at receptor level. First, homozygous mutant fatt/fatt mice carry spontaneous splice mutation causing deletion (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These are hyperphagic morbidly obese, but display only minimal changes...