KFO 217:  Hepatobiliary Transport and Liver Disease

• Subject Area: Medicine
• Term: from 2009 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 101434388

Liver diseases are of major clinical and socioeconomic importance due to their high prevalence with more than three million affected persons in Germany. They are often associated with or even caused by failure of hepatobiliary transport processes. Therefore, the central hypothesis say is that disturbances of hepatobiliary transport are not only primary causes but are also important "modifier" for the progression of many liver diseases. The aim of the Clinical Research Unit is to extend the pathophysiological knowledge of hepatobiliary transport processes. This shall be achieved by establishing pathways in order to support diagnosis as well as therapeutic and prognostic decisions.
The Clinical Research Unit aims to transfer approaches derived from system biology (genomics, proteomics, toponomics) into the clinical setting in order to establish a "computational and individualised medicine" for patients with cholestatic liver diseases. Translation from basic knowledge into clinical application is supported by the close interaction of participating scientist from clinical and basic sciences. Topics are: (1) development of routine-proofed methods for diagnosis of inherited and acquired cholestatic liver diseases; (2) establishment of automated methods for the quantitative analysis of subcellular distribution (Toponomics) of transport-relevant proteins in human liver slices in order to identify disease-specific Toponom- und protein patterns; (3) identification of genetic polymorphisms in transport-relevant proteins; (4) quantitative structure function analysis of transporter proteins and the role of genetic polymorphisms/mutations as disease modifier on a molecular level; (5) analysis of bile salt dependent immune modulation; (6) examination of the hepatoprotective role of organic osmolytes in patients with cholestasis or bile salt induce interferon resistance; (7) characterisation of molecular mechanisms and the development of therapeutic strategies in patients with post-surgery cholestasis; (8) investigations of cholestasis-associated pruritus including new therapeutic approaches.

• DFG Programme: Clinical Research Units

Projects

• Auswirkungen des gestörten Gallensalztransportes auf rote Blutkörperchen (Applicants Herebian, Diran ;  Lang, Ph.D., Philipp Alexander )
• Bedeutung des Gallensalzrezeptors TGR5 bei Lebererkrankungen (Applicant Keitel-Anselmino, Verena )
• Hepatobiliärer Transport und Lebererkrankungen (Applicant Häussinger, Dieter )
• Mechanismen des hepatisch bedingten Pruritus (Applicant Homey, Bernhard )
• Modulation der angeborenen Immunität durch Gallensäuren (Applicants Bode, Johannes Georg ;  Graf, Dirk )
• Molekulare Mechanismen und therapeutische Strategien bei postoperativer Cholestase (Applicant Donner, Markus )
• Mutationen hepatobiliärer Transporter als Ursache und Modulator von Lebererkrankungen (Applicant Keitel-Anselmino, Verena )
• Quantitative Struktur-Aktivitätsanalysen hepatobiliärer Transport-Systeme und deren pharmakologische Relevanz (Applicant Schmitt, Lutz )
• Toponomics-Diagnostik bei cholestatischen Lebererkrankungen (Applicants Berlage, Thomas ;  Häussinger, Dieter )
• Zentrale Plattform zur systematischen Bioanalytik hepatischer Prozesse (Applicants Köhrer, Karl ;  Mayatepek, Ertan )

• Spokesperson: Professor Dr. Dieter Häussinger
• Leader: Professorin Dr. Verena Keitel-Anselmino