- Metabolomics and Mass Spectrometry Studies
- Microbial Metabolic Engineering and Bioproduction
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Diet and metabolism studies
- Mass Spectrometry Techniques and Applications
- Isotope Analysis in Ecology
- Enzyme Catalysis and Immobilization
- RNA and protein synthesis mechanisms
- Tryptophan and brain disorders
- Peroxisome Proliferator-Activated Receptors
- CRISPR and Genetic Engineering
- Analytical Chemistry and Chromatography
- Gene Regulatory Network Analysis
- Insect Resistance and Genetics
- Advanced Chemical Sensor Technologies
- Amino Acid Enzymes and Metabolism
- Glycogen Storage Diseases and Myoclonus
- Biofuel production and bioconversion
Leiden University
2019-2024
Netherlands Metabolomics Centre
2019-2023
Centre for Human Drug Research
2021
University Medical Center Groningen
2018-2020
University of Groningen
2018-2020
The importance of lipids seen in studies metabolism, cancer, the recent COVID-19 pandemic and other diseases has brought field lipidomics to forefront clinical research. Quantitative comprehensive analysis is required understand biological interactions among lipid species. However, lipidomic often challenging due various compositional structures, diverse physicochemical properties, wide dynamic range concentrations systems. To study lipidome, a hydrophilic interaction liquid...
Analyzing metabolites using mass spectrometry can offer valuable insight into an individual's health or disease status. However, various sources of experimental variation affect the data, making robust quality control essential. In this context, we introduce mzQuality, a user-friendly software tool designed to evaluate and correct technical variations in spectrometry-based metabolomics data. MzQuality offers key features, such as batch correction, outlier identification, analysis...
Recent advances in metabolomics have enabled larger proportions of the human metabolome to be analyzed quantitatively. However, this usually requires use several chromatographic methods coupled mass spectrometry cover wide range polarity, acidity/basicity and concentration metabolites. Chemical derivatization allows principle a coverage single method, as it affects both separation detection metabolites: increases retention, stabilizes analytes improves sensitivity analytes. The majority...
Accurate reconstruction of metabolic pathways is an important prerequisite for interpreting metabolomics changes and understanding the diverse biological processes in disease models. A tracer-based strategy utilizes stable isotope-labeled precursors to resolve complex by tracing labeled atom(s) downstream metabolites through enzymatic reactions. Isotope enrichment analysis informative achieved counting total atoms acquiring mass isotopologue distribution (MID) intact metabolite. However,...
Refsum disease (RD) is an inborn error of metabolism that characterised by a defect in peroxisomal α-oxidation the branched-chain fatty acid phytanic acid. The disorder presents with late-onset progressive retinitis pigmentosa and polyneuropathy can be diagnosed biochemically elevated levels phytanate plasma tissues patients. To date, no cure exists for RD, but patients reduced plasmapheresis strict diet. In this study, we reconstructed fibroblast-specific genome-scale model based on...
Flavin adenine dinucleotide (FAD) and its precursor flavin mononucleotide (FMN) are redox cofactors that required for the activity of more than hundred human enzymes. Mutations in genes encoding these proteins cause severe phenotypes, including a lack energy supply accumulation toxic intermediates. Ideally, patients should be diagnosed before they show symptoms so treatment and/or preventive care can start immediately. This achieved by standardized newborn screening tests. However, many...
Abstract Starting with a comprehensive generic reconstruction of human metabolism, we generated high-quality, constraint-based, genome-scale, cell-type and condition specific models metabolism in dopaminergic neurons, the cell type most vulnerable to degeneration Parkinson ’ s disease. They are synthesis extensive manual curation biochemical literature on neuronal together novel, quantitative, transcriptomic targeted exometabolomic data from stem cell-derived, midbrainspecific, neurons vitro...
Abstract Constraint-based modelling can mechanistically simulate the behaviour of a biochemical system, permitting hypotheses generation, experimental design and interpretation data, with numerous applications, including metabolism. Given generic model, several methods have been developed to extract context-specific, genome-scale metabolic model by incorporating information used identify processes gene activities in given context. However, existing extraction algorithms are unable ensure...
A bstract Objective Phenylketonuria (PKU) is caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase, which primarily converts into tyrosine. Despite phenylalanine-deprived diet, many adult PKU patients display deficits in executive functions. These are hypothesised to be high cerebral and shortage monoaminergic neurotransmitters. Method To better understand relationship between plasma brain amino acid levels neurotransmitter biochemistry, we constructed computational model....
Quantitative inference of intracellular reaction rates is essential for characterising metabolic phenotypes. The classical experimental method measuring fluxes makes use stable-isotope tracing metabolites through the network, followed by mass spectrometry analysis. most common 13C-based flux analysis requires multidisciplinary knowledge in analytical chemistry, cell biology, and mathematical modelling, as well multiple independent tools handling data. Besides, usually carried out within a...
ABSTRACT Flavin adenine dinucleotide (FAD) and its precursor flavin mononucleotide (FMN) are redox cofactors that required for the activity of more than hundred human enzymes. Mutations in genes encoding these proteins cause severe phenotypes, including a lack energy supply accumulation toxic intermediates. Ideally, patients should be diagnosed before they show symptoms so treatment and/or preventive care can start immediately. This achieved by standardized newborn screening tests. However,...
ABSTRACT Refsum disease is an inborn error of metabolism that characterised by a defect in peroxisomal α-oxidation the branched-chain fatty acid phytanic acid. The disorder presents with late-onset progressive retinitis pigmentosa and polyneuropathy can be diagnosed biochemically elevated levels plasma tissues patients. To date, no cure exists for disease, but patients reduced plasmapheresis strict diet. In this study, we reconstructed fibroblast-specific genome-scale model based on recently...