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
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 |