Toxys, a spin-out company from the Leiden University Medical Center, provides next-generation genotoxicity testing services to rapidly identify potential carcinogenic properties of novel compounds during the early phases of product and drug development. Every novel chemical compound that is developed by pharmaceutical, chemical, cosmetics or food companies has to be rigorously tested for human health hazards before being considered safe for marketing. Current in vitro genotoxicity tests, which are an essential part of compound risk assessment, generally suffer from a low predictive value, which is a major financial drain for industry. To meet the demands from industry for better tests, Toxys is offering the ToxTracker assay. ToxTracker is a state-of-the-art stem cell-based reporter assay to rapidly identify various potentially carcinogenic properties of novel compounds with a superior sensitivity and specificity compared to the conventional in vitro (geno)toxicity tests available on the market. Toxys offers the ToxTracker assay as contract-based service and will provide the assay as shippable kit that can be purchased by companies with in-house testing facilities. In addition, the ToxTracker assay shows great potential as pharmaceutical screening tool. Toxys technology was developed at the Leiden university Medical Center. I was recently awarded with a NGI Pre-Seed grant to valorise the ToxTracker technology, leading to founding of Toxys in 2014. Currently, all Toxys activities are carried out at the LUMC. The mission of Toxys is to develop and commercialise mechanism-based in vitro toxicity assays that provide insights in the biological reactivity of compounds, which will improve human health hazard assessment and contribute to the development of safer products.

By combining whole genome transcription profiling, advanced genome editing tool and extensive stem cell expertise, we have developed various in vitro reporter systems that allow studying the mode of action of genotoxic chemicals. These reporter assays are used to provide a better understanding of how cells are responding to the induction of DNA damage.A panel of six GFP fluorescence-based reporter cell lines were combined in the ToxTracker assay. ToxTracker is a stem cell-based reporter assay that provides mechanistic insight in the mode of action of genotoxic compounds. The ToxTracker assay allows discrimination between direct interaction of compounds with DNA and induction of cellular oxidative stress, protein damage and general cellular stress. The assay has been extensively validated using various libraries of reference compounds. The ToxTracker assay is currently used for the identification of different potential carcinogenic properties of compounds during chemical human health hazard assessment.

Our DNA is continuously exposed to factors that can damage the DNA. DNA damage can lead to the induction of mutations and subsequently to various genetic diseases including cancer. At the department of Toxicogenetics we are studying the cellular mechanisms involved in these DNA damage-induced mutations and the role of the different DNA repair systems that protect against these mutations.

Title thesis: Synthesys and sorting of the Aquaporin-2 water channel.The Aquaporin-2 water channel plays an imporant role in resorption of water form the urine in the kidney. The research I performed during my PhD training was focussed on the cellular mechanisms that are involved in the biosynthesis and intracellular transport of the the water channels to the cell membrane of epithelial kidney cells.