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Project

Research in the domain of toxicology

The planned research activities are based on my experience accumulated in the field of bioanalysis. The research plan consists of further developing of my current research lines, as well as introducing new research directions in order to support a UA frontline (drug discovery and development) and emerging research domain (proteomics, genomics, and metabolomics). I hypothesize that biomarkers present in wastewater produced by communities provide objective information on spatio-temporal patterns on their lifestyle, disease and exposure to toxicants (= wastewater-based epidemiology). This will be tested through innovative research that will (i) select small-molecule biomarkers related to lifestyle, disease and exposure to toxicants; (ii) develop state-of-the-art bioanalytical assays to measure biomarkers in wastewater; and (iii) interpret the data with advanced statistical and modelling techniques. The aim is to implement wastewater-based epidemiology as a flexible and holistic tool to provide objective and timely information on the health status of whole communities. To allow long-term monitoring of alcohol and drug consumption in forensic contexts (e.g. driver's license regranting, organ transplantation procedure), I will continue my research to explore the use of keratinous matrices, i.e. hair and nails. I will investigate differences in hair and nails in accumulating substances. Furthermore, I want to establish reference values for biomarkers of drugs and alcohol in nails to be applied in a forensic context (as they also exist for hair). Therefore, studies with a high number of participants will be performed to correlate alcohol and drug biomarkers. I further plan to establish a robust bioanalytical platform to be used in the preclinical testing and pharmacokinetic profiling of candidate pharmaceuticals. I will focus on optimizing in vitro bioanalytical techniques for the evaluation of aspects of absorption (rapid equilibrium dialysis), distribution (protein binding assays) and metabolism (incubations with liver preparations) of xenobiotics. Furthermore, dedicated bioanalytical assays can/will be developed for the pharmacokinetic modeling of candidate pharmaceuticals (clearance, distribution volume,…). I aim to develop state-of-the-art bioanalytical procedures for metabolomics that combine multi-dimensional chromatographic and ion mobility separation techniques coupled to mass spectrometry (2D-LC-IM-QTOFMS) for the simultaneous detection of endogenous metabolites in a variety of biological matrices (cells, tissues, body fluids). This innovative technological platform will be used to (i) improve currently available bioanalytical metabolomics protocols in the Toxicological Centre for lipids and amino acids and (ii) develop innovative bioanalytical platforms to study subsets of the metabolome that are relevant for cardiovascular and inflammatory diseases: eicosanoids and steroids. Efforts will be made to optimize pre-analytical aspects including metabolism quenching and analyte extraction. These platforms can eventually be used in larger research contexts where metabolic information is crucial and can be integrated with other omics techniques to understand pathophysiological processes.
Date:1 Oct 2018 →  30 Sep 2023
Keywords:TOXICOLOGY
Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences