A5069972235- Metabolomics and Mass Spectrometry Studies
- Liver Disease Diagnosis and Treatment
- Drug-Induced Hepatotoxicity and Protection
- Health, Environment, Cognitive Aging
- Analytical Chemistry and Chromatography
- Birth, Development, and Health
- Diet and metabolism studies
- Nutritional Studies and Diet
- Liver Disease and Transplantation
- Spectroscopy and Chemometric Analyses
- NMR spectroscopy and applications
- Pharmacogenetics and Drug Metabolism
- Advanced Chemical Sensor Technologies
- Gut microbiota and health
- Spectroscopy Techniques in Biomedical and Chemical Research
- Traditional Chinese Medicine Studies
- Traditional Chinese Medicine Analysis
- Plant Toxicity and Pharmacological Properties
- Advanced MRI Techniques and Applications
- Pregnancy and preeclampsia studies
- Metabolism and Genetic Disorders
- Nutrition, Genetics, and Disease
- Gestational Diabetes Research and Management
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
Imperial College London
2015-2024
AstraZeneca (United Kingdom)
2014-2024
Hammersmith Hospital
2021-2022
AstraZeneca (Finland)
2021-2022
AstraZeneca (Canada)
2021-2022
University Hospital of Geneva
2018
Faculty (United Kingdom)
2016
Waters (United States)
2010
Bristol-Myers Squibb (United States)
2010
Pfizer (United States)
2007-2010
Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused single exposure–health effect relationships. The "exposome" concept encompasses the totality exposures from conception onward, complementing genome.Objectives: Early-Life Exposome (HELIX) project is a new collaborative that aims implement novel exposure assessment and biomarker methods characterize early-life multiple factors...
Essential to exposome research is the collection of data on many environmental exposures from different domains in same subjects. The aim Human Early Life Exposome (HELIX) study was measure and describe multiple during early life (pregnancy childhood) a prospective cohort associate these with molecular omics signatures child health outcomes. Here, we recruitment, measurements available baseline HELIX populations.The represents collaborative project across six established ongoing longitudinal...
Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution acute hepatic are largely unknown. Here, we aimed to investigate the impact Mer tyrosine kinase (MerTK) during ALF also examine how microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response.Flow cytometry, immunohistochemistry, confocal imaging gene expression...
Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver HE.
Abstract Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In Human Early Life Exposome (HELIX) project, multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting >100 chemical, outdoor, social and lifestyle assessed pregnancy childhood, with multi-omics profiles (methylome, transcriptome, proteins metabolites) childhood. We...
An integrated metabonomics study using high-resolution 1H NMR spectroscopy has been applied to investigate the biochemical composition of intact liver tissue (using magic angle spinning), extracts, and blood plasma samples obtained from control acetaminophen-treated mice. Principal components analysis was used visualize similarities differences in profiles. The time- dose-dependent effects acetaminophen were related drug toxicity, as determined histopathology. Metabolic lipid soluble...
The metabolic composition of fecal extracts provides a window for elucidating the complex interplay between mammals and their intestinal ecosystems, these metabolite profiles can yield information on range gut diseases. Here, metabolites present in aqueous humans, mice rats were characterized using high-resolution 1H NMR spectroscopy coupled with multivariate pattern recognition techniques. Additionally, effects sample storage preparation methods evaluated order to assess stability profiles,...
Harmonized data describing simultaneous exposure to a large number of environmental contaminants in-utero and during childhood is currently very limited.To characterize concentrations in pregnant women from Europe their children, based on chemical analysis biological samples mother-child pairs.We relied the Early-Life Exposome project, HELIX, collaborative project across six established population-based birth cohort studies Europe. In 1301 subjects, biomarkers 45 (i.e. organochlorine...
Hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC) permits the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP) chromatography. HILIC-UPLC-TOF-MS was investigated for global metabolic profiling rat urine samples generated in an experimental hepatotoxicity study galactosamine (galN) and concomitant investigation protective effect glycine. Within-run repeatability stability over a large sample batch (>200 samples, 60 h...
Environment and diet in early life can affect development health throughout the course. Metabolic phenotyping of urine serum represents a complementary systems-wide approach to elucidate environment-health interactions. However, large-scale metabolome studies children combining analyses these biological fluids are lacking. Here, we sought characterise major determinants child define metabolite associations with age, sex, BMI dietary habits European children, by exploiting unique biobank...
A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization target amines required minimal sample preparation resulted analytes excellent chromatographic mass spectrometric detection properties. The resulting method, which requires only 10 μL sample, provides...
As large scale metabolic phenotyping is increasingly employed in preclinical studies and the investigation of human health disease current LC-MS/MS profiling methodologies adopted for sample sets can result lengthy analysis times, putting strain on available resources. a these pressures rapid methods untargeted may have value where numbers samples require screening.To develop, characterise evaluate UHP-HILIC-MS-based method polar metabolites rat urine then extend capabilities this approach...
ABSTRACT Parkinson's disease (PD), an age-dependent neurodegenerative disease, is characterised by the selective loss of dopaminergic neurons in substantia nigra (SN). Mitochondrial dysfunction a hallmark PD, and mutations PINK1, gene necessary for mitochondrial fitness, cause PD. Drosophila melanogaster flies with pink1 exhibit defects cell are used as PD model. To gain integrated view cellular changes caused PINK1 pathway quality control, we combined metabolomics transcriptomics analysis...
Western populations use prescription and nonprescription drugs extensively, but large-scale population usage is rarely assessed objectively in epidemiological studies. Here we apply statistical methods to characterize structural pathway connectivities of metabolites commonly used detected routinely 1H NMR spectra urine a human study. were measured for two groups samples obtained from U.S. participants known The novel application total correlation spectroscopy (STOCSY) approach enabled rapid...
Spectroscopic profiling of biological samples is an integral part metabolically driven top-down systems biology and can be used for identifying biomarkers toxicity disease. However, optimal biomarker information recovery resonance assignment still pose significant challenges in NMR-based complex mixture analysis. The reduced signal overlap as achieved when projecting two-dimensional (2D) J-resolved (JRES) NMR spectra exploited to mitigate this problem and, here, full-resolution 1H JRES...
Preterm birth (PB) and fetal growth restriction (FGR) convey the highest risk of perinatal mortality morbidity, as well increasing chance developing chronic disease in later life. Identifying early pregnancy unfavourable maternal conditions that can predict poor outcomes could help their prevention management. Here we used an exploratory metabolic profiling approach (metabolomics) to investigate association between metabolites urine collected part prospective mother–child cohort Rhea study....
Predicting survival in decompensated cirrhosis (DC) is important decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a phenotype associated with 90-day survival.Two hundred forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC:...
Methotrexate (MTX) is a chemotherapeutic agent that can cause range of toxic side effects including gastrointestinal damage, hepatotoxicity, myelosuppression, and nephrotoxicity has potentially complex interactions with the gut microbiome. Following untargeted UPLC-qtof-MS analysis urine fecal samples from male Sprague-Dawley rats administered at either 0, 10, 40, or 100 mg/kg MTX, dose-dependent changes in endogenous metabolite profiles were detected. Semiquantitative targeted UPLC-MS...
Acute liver failure (ALF) is a life-threatening disease characterised by high-grade inflammation and immunoparesis, which associated with high incidence of death from sepsis. Herein, we aimed to describe the metabolic dysregulation in ALF determine whether systemic immune responses are modulated via lysophosphatidylcholine (LPC)-autotaxin (ATX)-lysophosphatidylcholinic acid (LPA) pathway.
Reduction of mortality associated with bacterial meningitis and postsurgical cerebral ventriculitis is dependent on early diagnosis institution appropriate therapy. Metabonomics rapidly defines metabolic profiles biological fluids through the use high-throughput analytical techniques combined statistical pattern recognition tools.Proton nuclear magnetic resonance (1H NMR)-based metabonomics was applied to (1) lumbar cerebrospinal fluid samples collected prospectively from a cohort patients...