Kullak-Ublick
Fakultäten » Medizinische Fakultät » Zentrum für Integrative Humanphysiologie (ZIHP) » ZIHP Zürcher Zentrum für Integrative Humanphysiologie » Kullak-Ublick
Completed research project
| Title / Titel | Regulation and functional characterization of transporters for drugs and endogenous substances in the human intestine | ||||||||
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| Abstract (PDF, 14 KB) | |||||||||
| Summary / Zusammenfassung | Intestinal epithelium selectively translocates molecules from the intestine to blood. Transport of nutrients, drugs, and other compounds is mediated by transporter proteins at enterocytic plasma membranes. Transporter expression levels determine the efficiency of absorption of their substrates. Little is known about the distribution and functional variability of transporters in normal physiology or intestinal diseases. We will characterize the molecular mechanisms that regulate intestinal transporter genes, and identify genetic variants in transporter genes that contribute to disease phenotypes. These studies should provide us with information about the causes of intestinal diseases and elucidate the changes in intestinal absorption in such pathologies. Further co-applicant: PD Dr. Jyrki Eloranta, Division of Clinical Pharmacology and Toxicology, USZ |
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| Publications / Publikationen | Jung D, Fried M, Kullak-Ublick GA. Human apical sodium-dependent bile salt transporter (SLC10A2) gene is regulated by the peroxisome proliferator-activated receptor alpha. J Biol Chem 2002; 277: 30559-30566Jung D, Fantin AC, Scheurer U, Fried M, Kullak-Ublick GA. Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 2004; 53: 78-84Eloranta JJ, Jung D, Kullak-Ublick GA. The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism. Mol Endocrinol 2006; 20: 65-79Meier Y, Eloranta JJ, Darimont J, Ismair MG, Hiller C, Fried M, Kullak-Ublick GA, Vavricka SR. Regional distribution of solute carrier mRNA expression along the human intestinal tract. Drug Metab Dispos 2007; 35: 590-594Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and in liver disease. Gastroenterology 2004; 126: 322-342Eloranta J, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 2005; 433: 397-412 | ||||||||
| Keywords / Suchbegriffe | mouse model, whole organ model, gene profiling technique, intestinal diseases, intestinal drug and nutrient absorption, transport proteins, nuclear receptors, transcriptional regulation | ||||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.zihp.uzh.ch/1610.php#15 http://www.research-projects.uzh.ch/p10888.htm |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung), EU, Foundation, Private Sector (e.g. Industry) This project is primarily supported by the University Research Priority Program "Integrative Human Physiology" at the University of Zurich. |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 2008 to Dec 2010 |