Molecular mechanisms of adverse outcome and translational biomarkers
Adverse drug reactions (ADRs) remain one of the major reasons for patient mortality and (early) drug withdrawal. Currently, different in vivo and in vitro models are used to assess the toxic potential of drugs in the pre-clinical phase. Unfortunately, the predictive value of this model does not fit the human patient situation completely and ADRs still occur unexpectedly.
To better predict this, we need to have more mechanistic insights behind the adverse outcome. During the projects, multiple techniques (e.g. confocal microscopy, genome wide screening, RNA interference, multiple cell models) will be used to investigate these mechanisms for approximately 2,000 drugs (figure 1). My project will try to link the molecular structure of drugs to the outcomes in different models. In the end, the overall goal is to develop a tool to better predict biomarkers that indicate adverse outcome after treatment with a drug.
Figure 1. A set of compounds that covers the drug-like chemical space will be screened on GFP reporter cell lines (1). This give result in dose-response relationships (2). We will try to link the cellular events to the molecular structure of drugs (3) and use this information to further to elucidate cellular mechanisms and build a tool to support biomarker prediction.
- 2018 - 2022
- Bob van de Water