Metabolomics is the study of small molecules (< 1400 Da) in the organism. Since it is most downstream of the cellular organisation, the metabolome is closest to the actual phenotype of the human, giving it a more accurate reflection of the health condition of the subjects monitored.
The use of Ultra Performant Liquid Chromatography in combination with High Resolution Mass Spectrometry provides a platform for untargeted metabolomics studies, generating big data. In combination with multi-variate statistics, these fingerprints are related to toxicological responses. As a result, new mechanisms of toxicity can be discovered, providing biomarkers for further research.
Liver toxicity is a frequent side effect of pharmaceutical compounds and toxicants. In vitro systems are valuable alternatives, but often lack in-depth information about the mode of action underlying the toxicological end-point.
The development of a new in vitro model using in vitro HepaRG liver cell lines in combination with UPLC-QTOF untargeted metabolomics investigates the different metabolic profiles related to different types of liver diseases, such as Non-Alcoholic Fatty Liver Disease (NAFLD), Cholestasis and oxidative stress.
The use of bio-informatics tools such as Principal Component Analysis, Partial Least Squares Discriminant Analysis and clustering algorithms deliver a classifier model to investigate the potential hepatotoxic effects of novel compounds.
This project is a Joint PhD in collaboration with the Research Group "In Vitro Toxicology and Dermatocosmetology" (Vrije Universiteit Brussel) and the AdREM Biomina research group.