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Gallstone disease: polymorphism screening and expression analyses of the ileal bile acid and lipid transporters and their transcription factors in gallstone disease

Gallstone disease (cholelithiasis) affects 15-20% of the Western civilization and causes an enormous economic burden. The formation of gallstones is very complex and is influenced by multiple risk factors. Diverse mechanisms are discussed as possible pathogenic elicitors. Our study group analyzes the regulative factors of the bile acid transport in the terminal ileum (part of the small intestine). We could show that female normal weight gallstone carriers exhibit a diminished expression of all investigated bile acid transporters in contrast to healthy controls. Our recent investigations comprise the genetic background of this reduced expression with respect to possible genetic alterations in association to cholelithiasis. Another risk factor for gallstone development is a disturbed cholesterol homeostasis. Here we focus our research on the expression of the intestinal cholesterol transporters. Our aim is to contribute to the elucidation of the various mechanisms of gallstone disease in diverse risk groups. 
 
Major Projects
  • Expression of intestinal bile acid transporters and relevant transcription factors
  • Genetic defects of intestinal bile acid absorption in gallstone carriers
  • Expression of intestinal cholesterol transporters and relevant transcription factors
Dr. Simone Harsch

phone: ++49-711-8101 3736

Selected References
  • Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange EF. Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers. J Lipid Res. 2006; 47(1):42-50.
  • Renner O, Harsch S, Strohmeyer A, Schimmel S, Stange EF. Reduced ileal expression of OSTalpha-OSTbeta in non-obese gallstone disease. J Lipid Res. 2008; 49(9):2045-54.
  • Holzer A, Harsch S, Renner O, Strohmeyer A, Schimmel S, Wehkamp J, Fritz P, Stange EF. Diminished expression of apical sodium-dependent bile acid transporter in gallstone disease is independent of ileal inflammation. Digestion. 2008; 78(1):52-9
  • Renner O, Harsch S, Schaeffeler E, Schwab M, Klass DM, Kratzer W, Stange EF. Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2): novel haplotype block including six newly identified variants linked to reduced expression. Hum Genet. 2009; 125(4):381-91.
  • Renner O, Harsch S, Schaeffeler E, Winter S, Schwab M, Krawczyk M, Rosendahl J, Wittenburg H, Lammert F, Stange EF. A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PLoS One. 2009; 4(10):e7321.
Major Networks and Collaborations
  • Lammert, F. Department of Medicine II, Saarland University Hospital, Homburg, Germany.
  • Wittenburg, H. Department of Gastroenterology and Hepatology, University of Leipzig, Leipzig, Germany.
  • Kratzer, W. Department of Medicine I, University Hospital of Ulm, Ulm, Germany.
  • Klass, D. Department of Medicine I, University Hospital of Ulm, Ulm, Germany.

Curriculum Vitae Simone Harsch, PhD

Affiliation
Graduate biologist

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
70376 Stuttgart Germany
phone: +49-711-8101 3736
fax: +49-711-85 92 95
email: simone.harsch@ikp-stuttgart.de
Education and Professional Career
1987-1995 Study of biology, University of Hohenheim
1995 Diploma
1996-2000 PhD student, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart
2000 Doctor’s degree
2000 Postdoc, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart
2001-2003 Postdoc, Clinical Pharmacology University of Tuebingen
2003-present Postdoc, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart