Liver Regeneration

In the second funding period, this research project will be pursued within Unit 3.2 Hepatobiliary Regeneration.

Objectives

The liver has an enormous regenerative potential. However, conditions like persistent infection with hepatotropic viruses (HBV and HCV) or sustained toxic liver damage can exhaust the liver´s regenerative capacity and eventually culminate in chronic liver failure. We are using genetic approaches to characterize how the proliferation of hepatocytes is controlled during liver regeneration. Ultimately, our research should contribute to the development of new therapeutics which can increase the regenerative potential of the liver.

Research Focus

Our research group is taking advantage of genetic approaches in order to study the regulation of liver regeneration. The liver has tremendous potential to regenerate following tissue damage caused by toxins or infection. It is unique in that – in contrast to many other epithelial organs – differentiated hepatocytes, which normally reside in the Go phase of the cell cycle, can re-enter the cell cycle subsequent to liver damage and give rise to new hepatocytes. However, when chronic liver damage occurs (e.g. chronic viral hepatitis), there is exhaustion of the regenerative capacity of hepatocytes and only partial compensation by a stem cell compartment (bipotential liver progenitor cells). The consequence is chronic liver failure, which represents a major health problem worldwide. We have established a unique system which allows in vivo RNA interference screens to be performed in order to identify positive and negative regulators of liver regeneration. Using our in vivo RNAi screening platform, we are characterizing new cellular signalling networks which regulate the proliferation of hepatocytes during chronic liver damage. The ultimate aim of our work is to translate the genetic information obtained into new pharmacological strategies which can increase the liver’s regenerative potential during chronic liver damage. Such therapies hold out great promise for prolonging patients’ survival until they are eligible for definite treatment by liver or hepatocyte transplantation.

Collaborations

  • N. Malek, Hannover Medical School, REBIRTH RG ‘Proliferation Control’
  • A. Gossler, Hannover Medical School, REBIRTH RG ‘Organogenesis/Notch signaling’
  • K. L. Rudolph, University of Ulm, ‘Stem cell regulators’
  • P. Schirmacher, University of Heidelberg, ‘Histopathology of murine liver carcinomas’
  • A. Vogel, Hannover Medical School, ‘RNAi screens for Rapamycin sensitivity- and resistance genes’
  • T. Greten, Hannover Medical School, ‘Conditional RNAi to modulate the expression of endogenous tumor antigens’

Further Research Projects

  • Joint Research Group ‘Chronic Infection and Cancer’. Funded by the German Research Foundation and the ‘Helmholtz Association Impuls und Vernetzungsfond’ (located at the HZI Braunschweig and Hannover Medical School)

Teaching

  • L. Zender is lecturer for the Ph.D. programme ‘Regenerative Sciences’ (seminars + tutorials)

Equipment and Service Facilities

[Please find a list of all available equipment here]

Publications

[Please find the publications of this workgroup here]

Staff

Zender, Lars Prof. Dr. Zender.Lars (at) mh-hannover.de
Wüstefeld, Torsten Dr. Wuestefeld.Torsten (at) mh-hannover.de
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