Prof. Dr. Tom Lüdde

 

Inflammation and Cancer, Animal Models, Cell Biology/Genetics, miRNAs/Biomarkers

In our lab, we are trying to understand what mechanisms are linking cell death with chronic inflammation, fibrosis and finally cancer development in liver disease. Studying the role of the IKK complex and the Kinase TAK1 in liver parenchymal cells in vivo, we turned our attention towards the activation of different modes of programmed cell death in chronic liver disease. We are trying to understand, which pathogenic stimuli are activating apoptosis vs. necroptosis in the liver, how these distinct forms of cell death regulate inflammatory responses and regeneration and finally how these processes control fibrosis (activation of hepatic stellate cells) and cancer development. We are currently expanding these studies towards other organs (pancreas, biliary system) and want to focus on biochemical aspects of the regulation of RIP proteins, which are master regulators of different cell death pathways. Finally, we are examining the function of miRNAs in these respective processes.

 

Expertise

• Inflammation and Cancer (Signaling, TNF pathway, NF-kappaB, IKK complex)
• Animal Models (conditional knockout lines of diverse genes in the TNF pathway)
• Cell biology/Genetics (proliferation, apoptosis, necroptosis, tumor genetics, DNA damage)
• miRNAs/biomarkers (miRNA Regulation and Function, extraction and analyses from serum, translational studies)

 

Need

• Help with proteomics analyses to identify novel intercellular mediators between cell death and inflammation.
• Molecular tools for systematic analyses of inflammatory mediators (Multiplex assay etc.).
• Cytogenetics and next generation sequencing for addressing genetic aberrations in tumours.
• To develop and/or characterize new specific small molecule inhibitors against mediators of cell death.

 

References

1. Bettermann K, Vucur M, Haybaeck J, Koppe C, Janssen J, Heymann F, Weber A, Weiskirchen R, Liedtke C, Gassler N, Müller M, de Vos R, Wolf MJ, Boege Y, Seleznik GM, Zeller N, Erny D, Fuchs T, Zoller S, Cairo S, Buendia MA, Prinz M, Akira S, Tacke F, Heikenwalder M, Trautwein C, Luedde T. TAK1 suppresses a NEMO-dependent, but NF-kappaB-independent pathway to liver cancer. Cancer Cell 2010; 17(5):481-96.

2. Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, Janssen J, Koppe C, Knolle P, Castoldi M, Tacke F, Trautwein C, Luedde T. micro-RNA-profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology 2011; 53(1):209-18.

3. Roderburg C, Luedde M, Cardenas DV, Vucur M, Mollnow T, Zimmermann HW, Koch A, Hellerbrand C, Weiskirchen R, Frey N, Tacke F, Trautwein C, Luedde T. miR-133a mediates TGF-β-dependent de-repression of collagen-synthesis in hepatic stellate cells during liver fibrosis. J Hepatol. 2013; 58(4):736-42.

4. Vucur M, Reisinger F, Gautheron J, Janssen J, Roderburg C, Vargas Cardenas D, Kreggenwinkel K, Koppe C, Hakem R, Unger K, Weber A, Gassler N, Luedde M, Frey N, Neumann UP, Tacke F, Trautwein C, Heikenwalder M, Luedde T. RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling Caspase-8-and JNK-dependent compensatory cell proliferation. Cell Rep. 2013 Aug 29;4(4):776-90.

5. Gautheron J, Vucur M, Reisinger F, Vargas Cardenas D, Roderburg C, Koppe C, Kreggenwinkel K, Schneider AT, Bartneck M, Neumann UP, Canbay A, Reeves HL, Luedde M, Tacke F, Trautwein C, Heikenwalder M and Luedde T. A positive feedback-loop between RIP3 and JNK controls Non-Alcoholic-Steatohepatitis. EMBO Mol Med. 2014 Jun 24;6(8):1062-74.