Contact

 

Prof. Dr. Henning Schulze-Bergkamen
Phone: +49 6221 565923
E-mail»

Dr. med. Bruno Köhler

Novel approches to...

 

overcome cell death resistance in gastrointestinal cancer.

NCT AG Cell Death Resistance

 

Our group/department has:

  • has demonstrated that increased apoptosis of hepatocytes coincides with strong hepatocyte proliferation resulting in spontaneous development of hepatocellular carcinoma in mice (DFG-funded project, Weber et al. Hepatology 2010). 
  • has been associated to the largest European research consortium on HCC (SFB/TRR77 Heidelberg/Hannover) in 2010 with its project addressing the role of the anti-apoptotic Bcl-2 protein Mcl-1 for the pathophysiology of liver diseases (Vick et al. Hepatology 2009).
  • proved that downregulation of the deubiquitinase CYLD i) contributes to apoptosis resistance of HCC cells (Urbanik et al. Int J Oncol 2011) and ii) triggers NF-kB activation and hepatocarcinogenesis in mice in vivo (Urbanik et al. J Hepatol 2012)
  • has been associated to the Heidelberg Clinical Research Unit KFO 227 on Colorectal Cancer with a subproject addressing the role of anti-apoptotic Bcl-2 proteins for colorectal cancer development and progression. In the context of the KFO 227, the AG i) has shown that suppression of anti-apoptotic Bcl-2 proteins regulates migration and invasion of colorectal cancer cells independent of cell death induction (Köhler et al. PLOS One 2013), and ii) has established various, intestine-specific Bcl-2 protein knockout mouse models.
  • The head of the AG is coordinator of the clinical cancer program colorectal and hepatocellular carcinoma and has profoundly contributed to the foundation of the Liver Cancer Center Heidelberg (LCCH) in 2012 and the comprehensive clinical trial program of the LCCH which links marker identification in HCC tissues with innovative clinical trials.

2009 – 2013

  • Koehler BC, Scherr AL, Lorenz S, Urbanik T, Kautz N, Elssner N, Welte S, Lorenzo Bermejo J, Jäger D, Schulze-Bergkamen H. Beyond cell death - Antiapoptotic Bcl-2 proteins regulate migration and invasion of colorectal cancer cells in vitro. PLOS One 2013. 8(10):e76446.
  • Urbanik T, Boger RJ, Longerich T, Becker K, Ehrenberg KR, Hövelmeyer N, Hahn M, Schuchmann M, Jäger D, Waisman A, Wörns MA, Schulze-Bergkamen H. Liver specific deletion of CYLDexon7/8 induces severe biliary damage, fibrosis and increases hepatocarcinogenesis in mice. Journal of Hepatology. 2012. 57:995-1003.
    (Editorial: Gautheron J, Luedde T. A novel player in inflammation and cancer: The deubiquitinase CYLD controls HCC development. Journal of Hepatology 2012. 57(5):937-9.)
  • Urbanik T, Koehler BC, Boger RJ, Woerns MA, Heeger S, Otto G, Hoevelmeyer N, Galle PR, chuchmann M, Waisman A, Schulze-Bergkamen H. Down-regulation of CYLD as a trigger for NF-κB activation and  mechanism of apoptosis resistance in hepatocellular carcinoma cells. International Journal of Oncology 2011. 38(1):121-31.
  • Weber A, Boger RJ, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Heikenwalder M, Schuchmann M, Schulze-Bergkamen H. Hepatocyte-specific deletion of the anti-apoptotic protein Mcl-1 triggers proliferation and hepatocarcinogenesis in mice. 2010. Hepatology. 51(4):1226-1236.
    (Editorial: Jost PJ, Kaufmann T. Cancer caused by too much apoptosis – an intriguing contradiction? Hepatology 2010. 51:1110-1112.)
  • Vick B, Weber A, Urbanik T, Krammer PH, Opferman JT, Schuchmann M, Galle PR, Schulze-Bergkamen H. Knock-out of Myeloid cell leukaemia-1 induces profound liver damage and increases apoptosis susceptibility of murine hepatocytes. Hepatology 2009. 49(2):627-36.
  • DFG: „Role of Mcl-1 for the pathophysiology of liver diseases“; Association of the project to the Transregio/SFB 77 („Liver Cancer – from molecular pathogenesis to targeted therapies”) in 2010
  • DFG: Subproject 8 of the Clinical Resarch Unit 227 (“Colorectal Cancer: From primary tumor progression towards metastases”): „The role of anti-apoptotic Bcl-2 proteins for colorectal cancer development and progression“
  • Merck Serono GmbH Darmstadt (2010-2014), Project: „Gastrointestinal carcinoma: Modulation of anti-apoptotic Bcl-2-Proteins to increase efficacy of targeted therapies”
  • Dietmar Hopp Foundation (2011-2013); Project: The role of the deubiquitinase CYLD for hepatocarcinogenesis
  • Medical Faculty Heidelberg: Postdoc-Fellowship to Bruno C. Köhler 2012-2014
  • Adolf-Kußmaul Prize, Southwest-German Association for Gastroenterology (2010)
  • First Author “Top 10%-Abstract” at the Annual Meetings “Digestive Disease Weeks”, San Diego, and “European Association for the Study of Liver Diseases”, Milano (2008)