Universiteit Leiden

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Research project

Drug safety Sciences

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

Contact
Bob van de Water

We translate basic mechanistic understanding of toxicity into meaningful in vitro predictive models for human chemical safety evaluation. Courses in drug safety sciences are provided in the BSc and MSc program of the Bio-Pharmaceutical Sciences studies and in the IMI SafeSciMET training program. Our department leads the EUToxRisk H2020 project where academic, industry, and regulatory partners work together to develop new animal-free strategies for chemical safety testing.

Under this theme we generally follow four approaches:

  1. High throughput microscopy for cellular adaptive stress response pathways in drug adversity. The Division has established a platform of ~fifty GFP-based reporter assays that allow the quantitative analysis of pathways of toxicity using high content microscopy in at a single cell level. These assays are used for high throughput quantitative toxicity testing in 2D and 3D cultures.
  2. Next generation human IPSC-derived reporter systems for image-based analysis of drug adversity. We currently invest strongly in a new version of the reporter panel where we make use of Crispr/Cas9-mediated genome engineering in IPSC cells.
  3. Integrated omics approaches for systems understanding of adverse outcome pathways. The data generated in a) are integrated with omics data including transcriptomics and phospho-proteomics. This allows us to unravel pathways of toxicity.
  4. Mathematical modelling of adverse outcome pathways. The data we jointly generate with other labs involved in EUToxRisk, including our own image data, serves as input for modeling approaches to unravel adverse outcome pathways (AOP).

 

High throughput microscopy analysis of NRF2 pathway response to DEM exposure

fig%205%20ox%20stress.pdf

 

 

Connection with other research