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Translational Hepatology, Cholestasis, pH regulation

Research interests

The pathophysiology of immune-mediated cholangiopathies, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and IgG4-related cholangitis (IRC), is complex, multifactorial and to date remains partially understood.

In health, cholangiocytes lining the bile ducts are responsible for the conditioning of canalicular bile through the secretion of a bicarbonate-rich fluid, thereby generating flow, controlling pH and protecting the luminal epithelial lining from chemical stress. In disease, this alkaline secretory fluid appears insufficient at deprotonating hydrophobic apolar bile acids resulting in membrane permeation and cytotoxicity. Therefore, detailed understanding of the molecular mechanisms underlying biliary pH regulation is of interest.

The cellular machinery involved in pH regulation includes carbonic anhydrase enzymes, transporters of the solute carrier (SLC) family, and intra- and extracellular pH sensors. Under physiological conditions this cellular machinery creates a closed-loop permitting pH homeostasis.

We hypothesize that pH dysregulation is a common occurrence in cholestatic liver diseases, such as PBC, PSC, IRC and possibly even cystic fibrosis-related liver disease (CFLD). Using gene expression profiling and functional microscopy experiments I investigate the molecular targets involved in biliary pH regulation and aim to exploit these as a therapeutic strategy for cholestatic liver diseases.

Collaborations and top research areas from the last five years

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