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Project T

Project T

 

 

Name:

Prof. Dr. Seidler

 

Institution:

Department of Gastroenterology and Hepatology

 

Telephone:

0511-532-9426

 

Internet:

Homepage

 

Research focus:

Our group studies the functional role and regulation of newly identified ion transport proteins in the gastrointestinal tract. The goal is to better understand the complex regulation of the ion transport pathways that are involved in the secretory and absorptive functions of the gastric, intestinal and biliary epithelium, to define the molecular and cellular defects in genetic diseases in which these proteins are dysfunctional, and to find new targets for drug development for some of the most prevalent gastrointestinal diseases - acute and chronic diarrhea, peptic and cholestatic diseases.

 

Projects:

  1. Structure-function relationsships and protein-protein interactions in the regulation of the transport proteins for intestinal salt absorption and anion secretion

  2. Mechanisms of volume regulation in gastrointestinal cells

  3. Adaptive mechanisms in the gastrointestinal tract after selective knockout of transport and regulator proteins for gastrointestinal salt and nutrient transport.

The projects are funded by the DFG (Deutsche Forschungsgemeinschaft), the BMBF (Ministerium für Bildung und Forschung), Aventis Pharma and Merck Pharma

 

Group members:

PD Dr. rer. nat. Michael Fährmann, biologist (faehrmann.michaelmh-hannover.de)
Dr. med. Oliver Bachmann, physician scientist (bachmann.olivermh-hannover.de)
Dr. rer. nat. Brigitte Riederer, biochemist (riederer.brigittemh-hannover.de)
Dr. med. Serhan Karvar, physician scientist (serhan.karvargmx.de)
Marc-Andre Kaufhold, PhD student (Kaufhold.Marcmh-hannover.de)
Tang Xixiang, M.D. M.Sc. Research fellow (tangxixianghotmail.de)
Maaß, Sabine, technician (Maass.annemh-hannover.de)
Schulz, Kirsten, technician (Schulz.Kirstenmh-hannover.de)
Krabbenhöft, Anja, technician (Krabbenhoeft.Anjamh-hannover.de)
Engelhardt, Regina, technician (Engelhardt.Reginamh-hannover.de)
Schuberth, Bettina, secretary (schuberth.bettinamh-hannover.de)

 

Methods:

Organ and cell physiology in transgenic mice: Mini-Ussing-chamber techniques, pH-stat titration, isotope flux studies, isolation and primary culture of gastrointestinal cells, measurement if secretion in single cells, single cell- and video-fluoromicroscopy, confocal microscopy, primary cell and tranfected cell cultures Molecular Biology: cloning, DNA and RNA preparation, Northern blotting, quantitative RT-PCR, recombinant DNA technology, adenovirus-and liposomal gene transfer, Protein Chemistry: Antibody generation, Western blotting, phosphorylation studies.

 

Key References:

  1. Pfeifer, A., A. Aszodi, U. Seidler, P. Ruth, F. Hofmann, und R. Fässler. 1996. Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II. Science 274:2082-2087

  2. Seidler, U. I. Blumenstein, D. Viellard-Baron, H. Rossmann, A. Kretz, W. Colledge, M. Evans, R. Ratcliff, und M. Gregor. 1997. A functional CFTR protein is required for cAMP-, cGMP-, and Ca2+- dependent stimulation of mouse intestinal HCO3- secretion. J. Physiol. (Lond.) 505.2:411-423

  3. Rossmann, H., O. Bachmann, D. Vieillard-Baron, M. Gregor und U. Seidler. 1999. Na+HCO3- cotransport and expression of NBC1 and NBC2 in rabbit gastric parietal and mucous cells. Gastroenterology 116:1389-98

  4. Sonnentag, Th., W.-K. Siegel, O. Bachmann, H. Rossmann, *A. Mack, *H.-J. Wagner, M. Gregor und U. Seidler. 2000. Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells. Am. J. Physiol. 279: G40-G48

  5. Jacob, P., S. Christiani, H. Rossmann, G. Lamprecht, D. Vieillard-Baron, R. Müller, M. Gregor und U. Seidler. 2000. Role of Na+HCO3- cotransporter NBC1, Na+/H+ exchanger NHE1 and carbonic anhydrase in rabbit duodenal HCO3- secretion. Gastroenterology 119(2): 406-419

  6. Rossmann, H., Th. Sonnentag, B. Seidler, O. Bachmann, W.-K. Siegel, D. Vieillard-Baron, M. Gregor, und U. Seidler. 2001. Differential expression and regulation of Na+/H+-exchanger isoforms in rabbit parietal and mucous cells. Am. J. Phys.281:G447-58

  7. Jacob, P., H. Rossmann, G. Lamprecht, A. Kretz, C. Neff, E. Lin-Wu, M. Gregor, J. Kere, und U. Seidler. 2002. Evidence that DRA is the brush border membrane Cl- /HCO3- exchanger in rabbit, rat and human duodenum. Gastroenterology, 122(3):709-24

  8. Fährmann, M., Heinzmann, A. und U. Seidler. 2002 CaMKII is activated and translocated to the secretory apical membrane during cholinergically conveyed gastric acid secretion. Cell Signal. 14(2):161-8

  9. Lamprecht G, Heil A, Baisch S, Lin-Wu E, Yun CC, Kalbacher H, Gregor M, Seidler U. The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange. Biochemistry. 2002 Oct 15;41(41):12336-42.

  10. Bachmann O, Rossmann H, Berger UV, Colledge WH, Ratcliff R, Evans MJ, Gregor M, Seidler U. cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3- cotransporter subtype pNBC1. Am. J. Physiol. 2003 Jan;284(1):G37-45.