Cholestasis constitutes a major manifestation of drug-induced liver injury, and is accompanied by inflammation and cell death. These processes are partly mediated by connexin hemichannels and pannexin channels, which facilitate paracrine cellular communication. This VUB-KULeuven joint doctoral thesis project will study the effects of drug-induced cholestasis on connexin hemichannels and pannexin channels. In order to do so, elaborate in vitro experimentation will be set up using 2 liver-derived in vitro models well-known to detect cholestatic drugs. In both these in vitro systems, the impact of cholestatic drugs on connexin hemichannels and pannexin channels will be studied at the transcriptional, translational and activity level. Besides generating novel fundamental insight into the mechanisms
of cholestasis, this doctoral thesis project will also assist in improving strategies to enhance in vitro prediction of drug-induced cholestasis. In particular, the use of connexin hemichannels and pannexin channels as in vitro indicators of cholestatic insults will be explored
by testing a number of drugs with various (non-)hepatotoxic properties as well as cosmetic ingredients, food ingredients and biocides with less characterized cholestatic potential. Overall, this doctoral thesis project will shed new light onto the mechanisms underlying drug-induced cholestasis and will yield an improved in vitro testing platform to detect cholestatic chemical compounds, especially drugs.
Effective start/end date1/11/1931/10/21

    Research areas

  • Drug-induced liver injury

    Flemish discipline codes

  • Hepatology

ID: 47754568