A5037896687- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Advanced Proteomics Techniques and Applications
- Spine and Intervertebral Disc Pathology
- Osteoarthritis Treatment and Mechanisms
- Psychoanalysis and Psychopathology Research
- Chemical Synthesis and Analysis
- Pulmonary Hypertension Research and Treatments
- Ubiquitin and proteasome pathways
- Breast Cancer Treatment Studies
- Musculoskeletal pain and rehabilitation
- Metabolomics and Mass Spectrometry Studies
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- NF-κB Signaling Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Multiculturalism, Politics, Migration, Gender
- Mass Spectrometry Techniques and Applications
- Middle East Politics and Society
- Diabetes Treatment and Management
- Bone health and treatments
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Cancer Treatment and Pharmacology
- Biochemical and Structural Characterization
Erasmus MC
2019-2022
University of British Columbia
2015-2021
Rotterdam University of Applied Sciences
2021
Erasmus University Rotterdam
2019
University of Groningen
2006-2016
Wolters Kluwer (Netherlands)
2011-2014
Boehringer Ingelheim (Germany)
2013
Helios Hospital Bad Saarow
2010
University Medical Center Groningen
2006
Leiden University
2006
Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling structural environment of cells tissues. For drug targeting proteases, selectivity for individual molecules is highly desired can be met by high yield active site specificity profiling. Using throughput Proteomic Identification protease Cleavage Sites (PICS) method to simultaneously profile both prime non-prime sides cleavage sites nine human MMPs, we...
Abstract Antigen receptor signalling activates the canonical NF-κB pathway via CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in activation B-cell lymphoma subtypes. To identify new human substrates, we compare B cells from only known living mut/mut patient with healthy +/ mut family members using 10-plex Tandem Mass Tag TAILS...
Modern biomarker and translational research as well personalized health care studies rely heavily on powerful omics' technologies, including metabolomics lipidomics. However, to translate lipidomics discoveries into a high-throughput clinical setting, standardization is of utmost importance. Here, we compared benchmarked quantitative platform. The employed Lipidyzer platform based lipid class separation by means differential mobility spectrometry with subsequent multiple reaction monitoring....
Matrix solid-phase dispersion (MSPD) is a new sample pretreatment for solid samples. This technique greatly simplifies but, nonetheless, the extracts often still require an extra cleanup step that both laborious and time-consuming. The potential of combining MSPD with molecularly imprinted extraction (MISPE) was investigated in this study. Liver samples were ground mortar C18 sorbent homogenized mixture packed into SPE cartridge placed on top MISPE cartridge. Subsequently, clenbuterol eluted...
Airway remodelling, characterised by increased airway smooth muscle (ASM) mass, subepithelial fibrosis, goblet cell hyperplasia and mucus gland hypertrophy, is a feature of chronic asthma. Increased arginase activity could contribute to these features via formation polyamines l -proline downstream the product -ornithine, reduced nitric oxide synthesis. Using specific inhitibor 2(S)-amino-6-boronohexanoic acid (ABH), we studied role in remodelling using guinea pig model Ovalbumin-sensitised...
ABSTRACT Enteroviruses encode proteinases that are essential for processing of the translated viral polyprotein. In addition, also target host proteins to manipulate cellular processes and evade innate antiviral responses promote replication infection. Although some protein substrates enterovirus have been identified, full repertoire targets remains unknown. We used a novel quantitative in vitro proteomics-based approach, termed t erminal mine i sotopic l abeling s ubstrates (TAILS),...
Airway inflammation and remodeling are major features of chronic obstructive pulmonary disease (COPD), whereas hypertension is a common comorbidity associated with poor prognosis. Recent studies in animal models have indicated that increased arginase activity contributes to asthma, including allergen-induced airway eosinophilia mucus hypersecretion. Although cigarette smoke lipopolysaccharide (LPS), risk factors for COPD, may increase expression, the role COPD unknown. This study aimed...
Abstract Controlled macrophage differentiation and activation in the initiation resolution of inflammation is crucial for averting progression to chronic inflammatory autoimmune diseases. Here we show a negative feedback mechanism proinflammatory IFN-γ macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12). Through C-terminal truncation at 135Glu↓Leu136 receptor-binding site was efficiently removed thereby reducing JAK-STAT1 signaling macrophages. In acute...
The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning lateral anteroposterior axes were derived high-resolution spatial proteomes intact young cadaveric lumbar IVDs. They revealed novel region-specific regulatory activities displayed potential paths...
In healthy skin, epidermis and dermis are anchored together at the dermal-epidermal junction (DEJ), a specialized basement membrane pivotal for skin integrity function. However, increased inflammation in DEJ is associated with disruption separation of this sub-epidermal blistering. Granzyme B (GzmB) serine protease secreted by immune cells. Dysregulated may lead to GzmB accumulation proteolysis extracellular milieu. Although elevated observed level inflammatory blistering conditions, present...
Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes mortality and disability worldwide. The disease characterized by plaques, heterogeneous deposits lipids, necrotic debris in vascular wall, which grow gradually may remain asymptomatic decades. However, at some point plaque can evolve to high-risk phenotype, trigger cerebrovascular event. Lipids play key role development progression atherosclerosis, but nature their involvement not fully understood. Using...
Este estudio tuvo como objetivo identificar, en las materias de cursos del área formación docente Educación Básica, aspectos relacionados con la investigación científica para estudiantes pregrado. Se trata un cualitativo y documental. Los documentos analizados fueron matrices curriculares carreras Licenciatura Ciencias Naturales Universidad Federal Integración Latinoamericana - UNILA Brasil profesores Básica Trás-os-Montes Alto Douro UTAD Portugal. En se analizaron 44 disciplinas 45. ambas...
l-tryptophan induces IDO (indoleamine 2,3-dioxygenase) 1-dependent vasodilation. IDO1 is expressed in placental endothelial cells and downregulated preeclampsia. Hypothesizing that this may contribute to diminished perfusion, we studied l-tryptophan-induced vasodilation healthy early-onset preeclampsia arteries, focusing on kynurenine pathway alterations. Despite downregulation, metabolite concentrations (measured with ultra-performance liquid chromatography-tandem mass spectrometry) were...
Abstract Background While thyroxine (T4), 3,3’,5-triiodothyronine (T3), and 3,3’,5’-triiodothyronine (rT3) have routine methods available for evaluating patients with suspected thyroid disease, appropriate the measurement of other hormone metabolites (THMs) are lacking. The effects iodothyronines or iodothyroacetic acids therefore less explored. To better understand (patho)physiological role THMs, a robust method to measure in serum single analysis is needed, including associated reference...
The data described provide a comprehensive resource for the family-wide active site specificity portrayal of human matrix metalloproteinase family. We used high-throughput proteomic technique PICS (Proteomic Identification protease Cleavage Sites) to comprehensively assay 9 different MMPs. identified more than 4300 peptide cleavage sites, spanning both prime and non-prime sides scissile bond allowing detailed subsite cooperativity analysis. were expanded by kinetic analysis using set 6...
Dysregulated protease activity is thought to cause parenchymal and airway damage in chronic obstructive pulmonary disease (COPD). Multiple proteases have been implicated COPD, identifying their substrates may reveal new mechanisms treatments. However, as interact with many that be inhibitors or themselves, these webs of interactions make the wider consequences therapeutically targeting difficult predict. We therefore used a systems approach determine COPD airways. Protease were determined by...
A novel solid-phase synthesis strategy toward succinylhydroxamate peptides, using an appropriately protected hydroxamate building block, is described. Rapid and efficient access gained to amine-functionalized which can be decorated with, for instance, a fluorescent label. In addition, we demonstrate on-resin of biotinylated photoactivatable peptide, used as activity-based probe matrix metalloproteinases ADAMs.
Abstract Zinc‐dependent metalloproteinases such as matrix (MMPs) and A disintegrin (ADAMs) are potential therapeutic targets in many diseases. To better understand their complex role health disease, new methodology for activity determination is under development. This concept gives an overview of the available methods activity‐based proteomic research on these enzymes. magnified image Metzincins a family zinc(II)‐dependent with well known members (ADAMs). largely responsible modulation...
The human genome encodes ∼20 mitochondrial proteases, yet we know little of how they sculpt the proteome, particularly during important events such as initiation apoptosis. To characterize global proteolysis refined our technique, terminal amine isotopic labeling substrates, for SILAC (MS-TAILS) to identify across mitochondria and parent cells in parallel. Our MS-TAILS analyses identified 45% proteome protein amino (N)-termini from 26% proteins, highest reported coverage N-terminome....
Abstract Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting tumour-suppressive effects, such as those by MMP8 various cancers. We mapped the substrates of to elucidate its previously shown tumour-protective role oral tongue squamous cell carcinoma (OTSCC). overexpressing (+) HSC-3 cells, demonstrated have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing secretomes + control cells with...