Research
Toxicogenomics can be described as the field of science that deals with the collection, interpretation, and storage of information about genome-wide molecular profiles within particular cells or tissue of an organism in response to toxic substances. Toxicogenomics combines toxicology with high content molecular profiling technologies for (epi)genomics, transcriptomics, proteomics and metabolomics. Toxicogenomics research aims to elucidate molecular mechanisms involved in the expression of toxicity, and to derive molecular patterns (i.e. molecular biomarkers) that predict toxicity or the individual susceptibility to it.
Research within the Department of Toxicogenomics is focused on the application of existing and emerging omics-technologies, evaluating cellular responses at the level of gene expression (transcriptomics), gene expression regulations (epigenetics and microRNA analysis), the protein level (proteomics) or the level of the metabolome (metabolomics). In doing so, different platforms and technologies are being applied and compared, including microarray technologies and next generation sequencing. A significant part of ongoing projects aims to optimise and integrate their application to human cellular models, for developing in vitro assays for toxicity prediction. The ultimate aim of projects like CarcinoGENOMICS, DETECTIVE, DiXa or research activities in the context of the Netherlands Toxicogenomics Centre (NTC) is the development of alternatives to animal testing for the toxicological evaluation of substances. More detailed descriptions of these projects can be found below.
A second line of research activities within the Department is focussing on the development of omics based biomarkers (e.g. protein-, metabolic- and gene expression profiles) to be applied in translational studies, specifically focusing on toxicological risk evaluation of dietary and environmental exposures and risk-benefit analysis. The nature and complexity of the data (in volume and variability) demands highly developed processes of automated handling, storage and data analysis. Therefore, a data storage and analysis infrastructure has been built which will be used by a growing team of bioinformaticians. The Department specifically aims to develop and implement relevant bioinformatics and biostatistical approaches, in order to retrieve the maximal amount of toxicological information generated through the omics-based studies.
Main research projects
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NewGeneris
NewGeneris: Newborns and Genotoxic exposure risks NewGeneris is an Integrated Project conducted within the European Union's 6th Framework Programme, priority area Food Quality and Safety. Its objective is to investigate the role of prenatal and early-life exposure to genotoxic chemicals present in food and the environment in the development of childhood cancer and immune disorders.
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NewGeneris WP8
Biomarkers of carcinogenic and immunotoxic risks - genomic effects Development of novel genomics-based biomarkers for genotoxic and immunotoxic risks in newborns. Modulation of gene expression will be investigated in PBMC, following exposure to a range of food-borne genotoxic and/or immunotoxic chemicals using DNA microarrays. Following this phase, differential gene expression will be investigated in selected mother-child sub-cohorts with known low and high exposures to specific compounds as determined by food-frequency-questionnaires. High-throughput analysis methods will be developed and subsequently applied biomonitoring cohorts. -
CARCINOGENOMICS
Development of a high throughput genomics-based test for assessing genotoxic and carcinogenic properties of chemical compounds in vitro -
Carcinogenic
A view on individual susceptibility This study aims at gaining more insight in inter individual variation in humans caused by exposure to carcinogenic substances. -
STW
Development of gene expression profiles from HepG2 cells for the correct prediction of true Genotoxic Carcinogens. By incubating HepG2 cells with model compounds of different classes, this project aims to identify the genes, whose expression is affected specifically by different classes of genotoxic compounds, in order to be used for the prediction of true genotoxic compounds. -
TUL Project
Analysis of exhaled air as indicator of oxidative stress in COPD patients Analysis of exhaled air as indicator of oxidative stress in COPD patients -
InVitroChem
Transcriptome profiling to predict the carcinogenic properties of chemicals The development of in vitro screens to predict the carcinogenic properties of chemicals. -
NTC
An applied system biology approach to predict chemical safety The primary goal of this project is to apply a system toxicology approach in order to predict a chemical safety of several compounds. This approach includes the use of highly sensitive methodologies that can reliably predict human carcinogen risk of new chemicals before they reach the market. -
Tul Blueberry 31964258T
Phytochemicals involved in the chemopreventive capacity of blueberry juice As blueberries are known to contain high levels of flavonoids and other antioxidant molecules, we recently performed a human dietary intervention study to establish their potential health promoting effect. The aim of the project is to reveal the molecular pathways involved in blueberry juice induced chemopreventive effects, by studying gene expression modulation in relation to the markers of antioxidant action that were previously established in a human intervention study. -
DNA damage
The role of DNA damage tolerance pathways in repair and mutagenicity of DNA adducts induced by polycyclic aromatic hydrocarbons Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens in animal models and are associated with the incidence of several human cancers. PAHs cover a wide range of structurally related compounds, but differ greatly in their potency for carcinogenicity, S-phase arrest, DNA damage formation, mutagenesis and modulation of gene expression. This project aims to unravel whether these differences can be explained by differential effects on DNA damage tolerance responses following exposure to the various PAHs. -
Embryotoxicity
Development of a transcriptomics based in vitro screening method to predict embryotoxicity, by using the embryonic stem cell test The aim of this study is to find biomarkers which can predict the embryotoxicity of a compound. Therefore, gene expression changes will be studied early in differentiation of embryonic stem cells into cardiomyocytes by using microarray techniques. By implementing this method in the validated EST the test duration will be reduced, which makes this genomics based in vitro method useful for high throughput screening. Furthermore it will save laboratory animals and costs. -
TFT
Project Translational Facility Toxicogenomics New concepts for determining toxicity -
EnviroGenomarkers
Genomics biomarkers of environmental health This project concerns the first large-scale application of the full range of –omics technologies in a population study. -
BE BASIC
Biobased solutions for a sustainable society -
Detective
Detection of endpoints and biomarkers of repeated dose toxicity using in vitro systems the DETECTIVE project will set up a screening pipeline of high content, high throughput as well as classical functional and “-omics” technologies to identify and investigate human biomarkers in cellular models for repeated dose in vitro testing. -
Hepatocarcinogenesis
Gene expression profiling of oxidative genotoxic compounds in hepatocarcinogenesis -
diXa
Data Infrastructure for Chemical Safety To create a large public data infrastructure of genomics signatures of drugs, industrial chemicals and cosmetics, and to develop pattern-matching bioinformatics and biostatistics tools to detect similarities among these signatures in order to describe all biological states induced with a chemical exposure, in terms of genomic signatures relevant for the human situation in vivo. -
ITFoM
IT Future of Medicine Data-rich, individualised medicine poses unprecedented challenges for IT, in hardware, storage and communication. We propose a data-driven, individualised medicine of the future, based on molecular/ physiological/anatomical data from individual patients. We shall make general models of human pathways, tissues, diseases and ultimately of the human as a whole. Individualised versions of the models, produced for each patient, will then be used to identify personalised prevention/therapy schedules and side effects of drugs.