A5009969152- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Diet and metabolism studies
- Epigenetics and DNA Methylation
- Organ Transplantation Techniques and Outcomes
- Immune responses and vaccinations
- Mass Spectrometry Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Fermentation and Sensory Analysis
- Immune Cell Function and Interaction
- Clostridium difficile and Clostridium perfringens research
- Renal Transplantation Outcomes and Treatments
- Cancer, Lipids, and Metabolism
- 14-3-3 protein interactions
- Dialysis and Renal Disease Management
- Cardiovascular and exercise physiology
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Horticultural and Viticultural Research
- Phytochemicals and Antioxidant Activities
- Liver Disease Diagnosis and Treatment
- COVID-19 Impact on Reproduction
Netherlands Metabolomics Centre
2016-2024
Leiden University Medical Center
2015-2024
Leiden University
2017-2024
Proteogenomics Research Institute for Systems Medicine
2023
National and Kapodistrian University of Athens
2009-2018
University of Crete
2011
Aristotle University of Thessaloniki
2010
University of Ioannina
2003-2005
Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and endothelial also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs MTs with CFs sarcomeric structures T-tubules, enhanced contractility, mitochondrial...
Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on outcome. However, mechanisms underlying gut–brain interaction implications for long-term recovery are largely elusive. Here, we tested hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, missing link along axis might be able to modulate experimental stroke. SCFA...
Abstract A common drawback of metabolic analyses complex biological samples is the inability to consider cell-to-cell heterogeneity in context an organ or tissue. To overcome this limitation, we present advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) combined with isotope tracing. This method allows mapping cell-type-specific dynamic changes central carbon metabolism a heterogeneous tissue...
Endothelial cells exposed to laminar shear stress express a thick glycocalyx on their surface that plays an important role in reducing vascular permeability and endothelial anti-inflammatory, antithrombotic, antiangiogenic properties. Production maintenance of this layer is dependent cellular carbohydrate synthesis, but its regulation still unknown. Approach Results: Here, we show biosynthesis the major structural component glycocalyx, hyaluronan, regulated by shear. Both vitro as well vivo,...
The facultative anaerobic polymorphic fungus Candida albicans and the strictly Gram-positive bacterium Clostridium difficile are two opportunistic pathogens residing in human gut. While a few studies have focused on prevalence of C. difficile-infected patients, nature interactions between these microbes has not been studied thus far. In current study, both chemical physical were investigated. presence albicans, was able to grow under aerobic, normally toxic, conditions. This phenomenon...
Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess at spatial resolution that acknowledges both heterogeneity and cellular dynamics its tissue microenvironment. Using multi-omics platform study cell-type-specific complex tissues, we describe the metabolic trajectories during nephrogenesis developing human kidney. Exploiting situ analysis of isotopic labeling, shift from glycolysis toward fatty acid β-oxidation...
Bacterial microbiota play a critical role in mediating local and systemic immunity, shifts these microbial communities have been linked to impaired outcomes illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, protozoa, are closely interlinked with the bacterial their host, yet collective during antibiotic perturbation illness remains be elucidated. We employed multi-omics factor analysis (MOFA) systematically integrate (16S...
Physical exercise modifies animal metabolism profoundly. Until recently, biochemical investigations related to focused on a small number of biomolecules. In the present study, we used holistic analytical approach investigate changes in human urine metabolome elicited by two sessions differing duration rest interval between repeated efforts. Twelve men performed three sets 80 m maximal runs separated either 10 s or 1 min rest. Analysis pre- and postexercise samples (1)H NMR spectroscopy...
Abstract Multinuclear ( 1 H, 13 C, 31 P) and multidimensional NMR spectroscopy was employed for the analysis of diacylglycerol (DAG) oil quantification its acylglycerols acyl chains composition. A number gradient selected two dimensional techniques (TOCSY, HSQC‐DEPT, HSQC‐TOCSY, HMBC) facilitated assignment complex one H‐ C‐NMR spectra. In several cases, aforementioned 2D‐NMR offered solid proof earlier assignments based on chemical shift changes induced by presence relative positions double...
Metabonomics is an established strategy in the exploration of effects various stimuli on metabolic fingerprint biofluids. Here, we present application 1H NMR-based metabonomics field exercise biochemistry. Fourteen men were assigned to either two training programs, which lasted 8 weeks and involved sets 80-m maximal runs separated by 10 s or 1 min rest. Analysis pre- postexercise serum samples, both at beginning end training, NMR spectroscopy subsequent multivariate statistical techniques...
Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions triggers antioxidant anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression inflammation widely employed as alternative the endogenous metabolite, can induce long-term transcriptional, epigenomic, metabolic changes, characteristic trained immunity. Dimethyl alters glycolytic mitochondrial...
Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not with syndrome, the underlying mechanisms still being unclear. We aimed to investigate role of gut microbiota induction dietary butyrate. performed antibiotic-induced depletion and fecal transplantation (FMT) APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like revealed that butyrate reduced appetite ameliorated high-fat diet-induced...
Abstract The growing disparity between the demand for transplants and available donor supply, coupled with an aging population increasing prevalence of chronic diseases, highlights urgent need development platforms enabling reconditioning, repair, regeneration deceased organs. This necessitates ability to preserve metabolically active kidneys ex vivo days. However, current kidney normothermic machine perfusion (NMP) approaches allow metabolic preservation only hours. Here we show that human...
Abstract The pathogenic success of Mycobacterium tuberculosis ( Mtb ) is tightly linked to its ability recalibrate host metabolic processes in infected macrophages. Since changes cellular intermediates or pathways also affect macrophage function response pathogens, we sought analyse specific alterations induced by infection. Stimulation macrophages with lysate lipopolysaccharide (LPS) a relative increase glycolysis versus oxidative phosphorylation. Cellular metabolomics revealed that...
Significance Nonresolving inflammation, a hallmark of sepsis and/or multi-organ failure, still poses challenge in medicine. The mortality rate is enormous, and so far no adequate curative therapy available. Here we identify previously unrecognized role the neuronal guidance protein semaphorin 7A transition to resolution processes severe systematic inflammation such as sepsis.
The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of cells. As reactive oxygen species (ROS) production has been associated with the phenotype, we hypothesized that increased ROS levels main intracellular redox molecule glutathione play role in induction immunity. Here show pharmacological inhibition an vitro model...
Delayed graft function is the manifestation of ischemia reperfusion injury in context kidney transplantation. While hundreds interventions successfully reduce experimental models, all clinical have failed. This explorative evaluation examined possible metabolic origins combining data from 18 pre- and post-reperfusion tissue biopsies with 36 sequential arteriovenous blood samplings over three study groups. These groups included living deceased donor grafts without delayed function. Group...
Abstract Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an immunological memory termed trained immunity . Here, we show that monocytes with a phenotype, due to exposure the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological genetic approaches PUFA synthesis lipoxygenase-derived LM essential for...
The key pathological signature of ALS/ FTLD is the mis-localization endogenous TDP-43 from nucleus to cytoplasm. However, gain function in cytoplasm still poorly understood since animal models recapitulating are missing.