Cellular communication as target and biomarker in liver disease and toxicity: from basic research towards clinical application

Cellular channels located at the plasma membrane consisting of connexin or pannexin proteins have recently emerged as major goal keepers of paracrine communication. In this respect, pioneering research from the candidate’s team over the past decade has shown that these channels specifically open in liver disease. This suggests a role as targets for the treatment of liver disease, which underlies the fifth most common cause of death worldwide. Thus far, the candidate’s team focused on acute liver toxicity, non-alcoholic steatohepatitis and liver fibrosis. The candidate’s team will extend these studies in the upcoming years by addressing other liver diseases, including cholestasis and liver cancer, in order to verify the generic applicability of connexin and pannexin channels as druggable targets. This will go hand in hand with the production and testing of next generation inhibitors of these cellular channels as novel drugs for the treatment of liver disease. In parallel, connexin and pannexin proteins as such will be explored as clinical biomarkers to support the diagnosis and prognosis of liver disease. This equally builds further on previous work from the candidate’s team, showing that the production of these proteins drastically alters upon liver pathology. Furthermore, connexins, pannexins and their channels will be tested as in vitro biomarkers to identify non- genotoxic liver carcinogenic chemicals. These research activities will shape the solid basis to pursue an international, interdisciplinary and intersectoral research program that will form a fertile soil for several doctoral and postdoctoral research projects. This will be aligned by an already initiated valorization track with the goal to leverage future clinical and pharmaceutical applications of connexins, pannexins and their channels as targets and biomarkers in liver disease and toxicity. The candidate’s research and team are now at a tipping point, where all critical mass, expertise and know-how have been captured, and high international recognition has been gained. In fact, the candidate’s team has been rapidly expanding over the past few years, mainly because of iterative acquisition of highly competitive European funding. Structural long-term Methusalem funding will consolidate growth of the candidate’s team and thereby strengthen its international position as a key research group. This will allow to establish an international center of excellence in the liver research field, which in turn will significantly increase the global visibility of the VUB. First and foremost, this will bring about promising perspectives for the large liver disease patient population worldwide.