Projects per year
Personal profile
specialisation
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
Projects
- 1 Active
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van de Graaf K.F.J. (Stan): metabolite dynamics and liver-centered organ crosstalk
van de Graaf, S., Appelman, M., Chen, H., Donkers, J., Hubers, L., van Niekerk, J., Roscam Abbing, R., Slijepcevic, D., van de Wiel, S., Oude Elferink, R., de Waart, R., Paulusma, C., Duijst, S., Beuers, U., Bolt, I., Vogels, E., In het Panhuis, W., Kunst, R., Wu, D., Trampert, D. C., Kersten, R., Groenen, C. & Nguyen, T.
1/06/2016 → …
Project: Research
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A beneficial response of fetal wound healing gone bad in the bile duct: The overarching cause of biliary atresia?
Trampert, D. C. & Beuers, U., Mar 2024, In: Journal of Hepatology. 80, 3, p. 387-389 3 p.Research output: Contribution to journal › Editorial › Academic › peer-review
Open Access -
Laminin 511-E8, an autoantigen in IgG4-related cholangitis, contributes to cholangiocyte protection
Trampert, D. C., Kersten, R., Tolenaars, D., Jongejan, A., van de Graaf, S. F. J. & Beuers, U., 1 Apr 2024, In: JHEP Reports. 6, 4, 101015.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
Targeting bile salt homeostasis in biliary diseases
Trampert, D. C., Kunst, R. F. & van de Graaf, S. F. J., 1 Mar 2024, In: Current opinion in gastroenterology. 40, 2, p. 62-69 8 p.Research output: Contribution to journal › Review article › Academic › peer-review
Open Access -
Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids
Kersten, R., Trampert, D. C., Hubers, L. M., Tolenaars, D., Vos, H. R., van de Graaf, S. F. J. & Beuers, U., 2023, In: Frontiers in immunology. 14, 1251134.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
IgG4-related cholangitis - a mimicker of fibrosing and malignant cholangiopathies
Kersten, R., Trampert, D. C., Herta, T., Hubers, L. M., Maillette de Buy Wenniger, L. J., Verheij, J., van de Graaf, S. F. J. & Beuers, U., Dec 2023, In: Journal of Hepatology. 79, 6, p. 1502-1523 22 p.Research output: Contribution to journal › Review article › Academic › peer-review
Open Access3 Citations (Scopus)