Dissertation
Mathematical modelling of cellular pathways contributing to drug- induced liver injury
Drug development is a lengthy and costly process. Many drugs fail clinical trials despite extensive preclinical tests on animals.
- Author
- E.J. Burgers
- Date
- 08 July 2026
- Links
- Thesis in Leiden Repository
Drug-induced liver injury (DILI) is a common reason for drugs to fail clinical trials or to be withdrawn from the market. To improve the prediction of DILI, we need to understand its underlying mechanisms. It has been suggested that activation of stress pathways within cells is an important indicator of DILI. To investigate these pathways and their effect on various cell fates, we applied computational methods, mostly by developing systems of ordinary differential equations (ODEs). We applied these ODE models to experimental data, primarily consisting of imaging data in which fluorescent protein expression was monitored over time in response to potential toxicants. In this thesis we demonstrate the useful interplay between experimental and computational approaches in biomedical research. The mathematical models developed in this work have increased our understanding of cellular pathways beyond what would have been possible with experimental data alone. Improving and expanding these models has the potential to further advance this field and thereby help DILI predictions in the future.