Project Schulz-Bergkamen

Principal Investigator:  H. Schulze-Bergkamen

"The role of Mcl-1 for the pathophysiology of liver diseases" 
The scientific focus of the group, which is located at the National Center of Tumor Diseases, Department of Medical Oncology (Director: Prof. Dr. Dirk Jäger), is the analysis of apoptosis signaling in cancer. In particular, the group deals with the role of the anti-apoptotic Bcl-2 protein Mcl-1 for liver homeostasis and hepatocarcinogenesis. Another main focus is to investigate the pleiotropic effects of the deubiquitinase CYLD for apoptosis signaling in liver cells and its role for the development of hepatocellular carcinoma (HCC). The group has already demonstrated that hepatocyte-specific deletion of the Bcl-2 protein Mcl-1 results in profound liver damage due to apoptosis induction. Notably, it was shown that liver injury in Mcl-1 negative livers is accompanied by hepatocellular proliferation and the spontaneous development of HCC. In association with the TRR77, the group plans to further analyse molecular determinants in apoptosis signaling pathways causing hepatocellular proliferation and hepatocarcinogenesis.

List of relevant publications

  1. Weber A, Boger R, 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. 51:1226-1236. Editorial: Jost PJ, Kaufmann T. Cancer caused by too much apoptosis – an intriguing contradiction? Hepatology. 51:1110-12
  2. 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. 2009. Hepatology. 49(2):627-36.
  3. Schulze-Bergkamen H, Weinmann A, Möhler M, Siebler J, Galle PR. Novel ways to sensitize gastrointestinal cancer to apoptosis. 2009. Gut. 58(7):1010-24.
  4. Koehler BC, Urbanik T, Vick B, Boger RJ, Heeger S, Galle PR, Schuchmann M, Schulze-Bergkamen H. TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies. 2009. World J Gastroenterology. 15(47):5924-35.
  5. Schulze-Bergkamen H, Fleischer B ,Schuchmann M, Weber A, Weinmann A, Krammer PH, Galle PR. Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. 2006. BMC Cancer. 6:232.
  6. Fleischer B*, Schulze-Bergkamen H*, Schuchmann M, Weber A, Biesterfeld S, Müller M, Krammer PH, Galle PR. Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma. 2006. International Journal of Oncology. 28(1):25-32. *Equal contribution.
  7. Kern MA, Haugg AM, Koch AF, Schilling T, Breuhahn K, Walczak H, Fleischer B, Trautwein C, Schulze-Bergkamen H, Stremmel W, Krammer PH, Schirmacher P, Müller M. Cyclooxygenase (COX)-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma. 2006. Cancer Research. 66(14):7059-66.
  8. Schulze-Bergkamen H, Schuchmann M, Fleischer B, Galle PR. The role of apoptosis versus oncotic necrosis in liver injury - facts or faith? 2006. Journal of Hepatology. 44(5):984-93.
  9. Gressner O, Schilling T, Lorenz K, Schulze-Schleithoff E, Koch A, Schulze-Bergkamen H, Candi E, Terrinoni A, Catani MV, Oren M, Melino G, Krammer PH, Stremmel W, Müller M. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. 2005. EMBO J. 24:2458-71.
  10. Herzer K, Grosse-Wilde A, Ganten T, Schulze-Bergkamen H, Krammer PH, Walczak H. Transforming Growth Factor beta can mediate apoptosis via the expression of TRAIL in human hepatoma cells. 2005. Hepatology. 42:183-92
  11. Schulze-Bergkamen H, Brenner D, Krueger A, Suess D, Fas SC, Frey CR, Dax A, Zink D, Büchler P, Müller M, Krammer PH. Hepatocyte Growth Factor induces Mcl-1 in primary human hepatocytes and inhibits CD95-mediated apoptosis via Akt. 2004. Hepatology. 39:645-654.
  12. Schulze-Bergkamen H, Krammer PH. Apoptosis in cancer – implications for therapy. 2004. Seminars in Oncology; 31:90-119.
  13. Schulze-Bergkamen H, Untergasser A, Dax A, Vogel H, Büchler P, Klar E, Lehnert T, Friess H, Büchler MW, Kirschfink M, Stremmel W, Krammer PH, Müller M, Protzer U. Primary human hepatocytes – a valuable tool for investigation of apoptosis and hepatitis B virus infection. 2003. Journal of Hepatology. 38(6):736-744.
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