Group: Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Key members: Denise Kratschmar, Katharina Beck, Silvia Inderbinen, Melanie Patt, Simon Stücheli, Alex Odermatt
Contact: Alex Odermatt,
Research activities: We investigate oxidoreductase enzymes involved in the metabolism of steroids, oxysterols and bile acids, as well as the signaling by such molecules through nuclear receptors. We showed that 11β-hydroxysteroid dehydrogenase type 1, besides converting cortisone to cortisol, metabolizes 7-ketocholesterol to 7β-hydroxycholesterol. Later we showed that this enzyme also reduces 7-ketolithocholic acid to chenodeoxycholic acid and ursodeoxycholic acid. In ongoing experiments, we investigate how 7-ketocholesterol is metabolized to bile acids, and how this enzyme affects oxysterol and bile acid homeostasis. Further, we develop in vitro assays to assess the activities of other oxidoreductases and for studying receptor-based transcriptional regulation in order to investigate physiological functions and disturbances caused by xenobiotics. Additionally, we develop methods for measuring biological samples such as plasma/serum, urine, tissues, cells and culture supernatants. We apply ultra-high pressure liquid chromatography mass spectrometry-based quantification of sterol molecules in these samples. We apply these methods for mechanistic investigations in cell models and in collaborations for preclinical and clinical studies related to cancer, renal and cardio-metabolic diseases.
Key papers related to ENOR:
Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids. Strajhar P, Tonoli D, Jeanneret F, Imhof R, Malagnino V, Patt M, Kratschmar D V, Boccard J, Rudaz S, and Odermatt A (2017) Toxicology, 381, 51-63.
11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice. Penno C A, Morgan S A, Rose A J, Herzig S, Lavery G G, and Odermatt A (2014) Mol Metab, 3, 554-564.
Quantification of multiple bile acids in uninephrectomized rats using ultra-performance liquid chromatography-tandem mass spectrometry. Penno C A, Arsenijevic D, Da Cunha T, Kullak-Ublick G A, Montani J-P, and Odermatt A. (2013) Anal Methods 5, 1155-1164.
Rapid hepatic metabolism of 7-ketocholesterol by 11β-hydroxysteroid dehydrogenase type 1. Schweizer R A S, Zürcher M, Balazs Z, Dick B and Odermatt A (2004) J. Biol. Chem., 279, 18415-18424.