A5049802073- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Blood Coagulation and Thrombosis Mechanisms
- Galectins and Cancer Biology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- S100 Proteins and Annexins
- Nanoparticle-Based Drug Delivery
- Signaling Pathways in Disease
- Chemokine receptors and signaling
- COVID-19 Clinical Research Studies
- Osteoarthritis Treatment and Mechanisms
- Cystic Fibrosis Research Advances
- Enzyme Production and Characterization
- Pneumocystis jirovecii pneumonia detection and treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Protein Hydrolysis and Bioactive Peptides
- Transplantation: Methods and Outcomes
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Endodontics and Root Canal Treatments
- Wound Healing and Treatments
Rega Institute for Medical Research
2015-2024
KU Leuven
2015-2024
Laboratory of Molecular Genetics
2021
Heidelberg University
2015
Ludwig-Maximilians-Universität München
2015
Fund for Scientific Research
2015
European Union
2015
Neutrophils are recognized as important circulating effector cells in the pathophysiology of severe coronavirus disease 2019 (COVID-19). However, their role within inflamed lungs is incompletely understood. Here, we collected bronchoalveolar lavage (BAL) fluids and parallel blood samples critically ill COVID-19 patients requiring invasive mechanical ventilation compared BAL fluid parameters with those mechanically ventilated influenza, a non-COVID-19 viral pneumonia cohort. Compared...
Abstract Objectives Emerging evidence of dysregulation the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID‐19). We isolated neutrophils from blood COVID‐19 patients receiving general ward care and hospitalised at intensive units (ICUs) to explore kinetics circulating factors important for migration activation. Methods Multicolour flow cytometry was exploited analysis differentiation activation markers. Multiplex ELISA...
To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9.Fluorogenic Dye-quenched (DQ)™-gelatin was used as substrate biochemical parameters (substrate enzyme concentrations, DMSO solvent concentrations) were optimized system. Various small-sized libraries (ChemDiv, InterBioScreen ChemBridge) heterocyclic, drug-like substances tested compared with prototypic...
Abstract Background and objective Non‐cystic fibrosis bronchiectasis ( NCFB ) is characterized by a vicious cycle of airway infection, inflammation structural damage with inappropriate mucus clearance. Our aim was to relate the value proteolytic enzymes, enzyme activity inflammatory markers disease severity symptoms in patients . Methods Sputum induction healthy controls performed. analysed for total differential cell count, CXCL8 (also known as interleukin‐8) tumour necrosis factor‐α TNF...
Abstract Matrix metalloproteinase 9 (MMP-9/Gelatinase B) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and plays a central role tumor cell invasion metastasis. Here we complemented mechanistic insights the cancer biology of MMP-9 investigated effects specific long-term loss-of-function, by genetic ablation, on PDAC initiation progression well-established KPC mouse model spontaneous PDAC. Tumor growth were analyzed histopathology IHC. Invasive cells was both vitro...
Introduction Wound healing is a complex process to restore homeostasis after injury and insufficient skin wound considerable problem in medicine. Whereas many attempts of regenerative medicine have been made for with growth factors cell therapies, simple pharmacological immunological studies are lagging behind. We investigated how fibrin hydrogels modulate immune cells molecules mice. Methods Physiological (3.5 mg/mL fibrinogen) were generated, biophysically analyzed stiffness protein...
Significance The loss of myelin around axons is a main pathological hallmark various neurological diseases. In early disease stages, this sheath restored through process called remyelination. Later, remyelination fails and becomes the major driver progression. Despite clear demand for remyelination-enhancing therapies, need currently unmet. Here we present oncostatin M receptor signaling its downstream effector molecule tissue inhibitor metalloproteinases-1 as decisive mediators successful...
Gelatinase B/matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) cleaves many substrates and is produced by most cell types as a zymogen, proMMP-9, in complex with the tissue inhibitor of metalloproteinases-1 (TIMP-1). Natural proMMP-9 occurs monomers, homomultimers heterocomplexes, but our knowledge about overall structure monomers multimers limited. We investigated biochemical, biophysical functional characteristics zymogen activated forms MMP-9 multimers. In contrast conventional notion...
Matrix metalloproteinases (MMPs), tissue inhibitors of (TIMPs), a disintegrin and metalloprotease with thrombospondin motifs [ADAM(TS)s] growth factors are involved in inflammation damage repair, all occurring inflammatory bowel disease (IBD). We studied the impact anti-inflammatory therapy infliximab on mucosal expression these remodeling genes patients IBD.Mucosal gene 23 MMPs, 4 TIMPs, 50 ADAM(TS)s, 158 was investigated 61 IBD before after first 12 controls, microarrays quantitative...
Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, associated with disease progression. In part, this due to MMP-9-mediated degradation of extracellular matrix, facilitating influx leukocytes into inflamed tissues invasion metastasis cancer cells. MMP-9 produced as proMMP-9 its propeptide subsequently removed by other proteases generate proteolytically active MMP-9. The significance pathologies triggered the development...
Matrix metalloproteinases (MMPs) are enzymes with critical roles in biology and pathology. Glycosylation, nitrosylation proteolysis known posttranslational modifications (PTMs) regulating intrinsically the activities of MMPs. We discovered MMP citrullination by peptidyl arginine deiminases (PADs) as a new PTM. Upon hypercitrullination, MMP-9 acquired higher affinity for gelatin than control MMP-9. Furthermore, hypercitrullinated proMMP-9 was more efficiently activated MMP-3 compared to...