Contact

 

Prof. Dr. Peter H. Krammer
Phone: +49 6221 42 3717

E-mail: p.krammer(at)dkfz-heidelberg.de

Sensitize tumor cells...

 

to cell death. 

Tumorimmunology/Immunogenetics

DKFZ
 
 
 

Our group/department has:

  • Translation: APG101, Apocept (CD95-Fc) has reached end of phase 2 in glioblastoma, shows an increase in progression free and overall survival, and may be active in GvHD, MDS and various other diseases.
  • CD95 signaling: New insights into the mechanisms of caspase-8 activation and apoptosis initiation have been unravelled (Schleich K, Warnken U, Fricker N, Oztürk S, Richter P, Kammerer K, Schnölzer M, Krammer PH, Lavrik IN. Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol Cell. 2012 Jul 27;47(2):306-19).
  • Oxidative signaling in T cells and T cell tumors: We have identified a novel molecular mechanism and enzymes that connect the Warburg effect and oxidative signaling. This elucidates a signaling pathway which had remained obscure for about 100 years since O. Warburg formulated his hypothesis (Kamiński MM, Sauer SW, Kamiński M, Opp S, Ruppert T, Grigaravičius P, Grudnik P, Gröne HJ, Krammer PH, Gülow K. T cell Activation Is Driven by an ADP-Dependent Glucokinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation. Cell Rep. 2012 Nov 29;2(5):1300-15). 
  • Novel regulators of NF-kB signaling in lymphocytes: We found catalytic and regulatory phosphatase units that regulate the activity of NF-kB. These findings have important implications for autoimmunity and cancer, both diseases in which NF-kB is involved (Brechmann M, Mock T, Nickles D, Kiessling M, Weit N, Breuer R, Müller W, Wabnitz G, Frey F, Nicolay JP, Booken N, Samstag Y, Klemke CD, Herling M, Boutros M, Krammer PH, Arnold R. A PP4 Holoenzyme Balances Physiological and Oncogenic Nuclear Factor-Kappa B Signaling in T Lymphocytes. Immunity. 2012 Oct 19;37(4):697-708).
  • Apoptosis sensitivity and resistance in cancer: We discovered two TCM (Traditional Chinese Medicine) anti-cancer compounds, Wogonin and Rocaglamide, and showed that they preferentially induce apoptosis in tumor cells in vitro and in vivo in mouse models, and we identified the cyclin-dependent kinase 9 (CDK9) as the direct molecular target of Wogonin. We also identified Prohibitin 1 and 2 as the direct target of Rocaglamide. (Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M. The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2. Chem Biol. 2012 Sep 21;19(9):1093-104).

2010 – 2013

  • Kamiński MM, Sauer SW, Kamiński M, Opp S, Ruppert T, Grigaravičius P, Grudnik P, Gröne HJ, Krammer PH, Gülow K. T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep. 2012 Nov 29;2(5):1300-15.
  • Brechmann M, Mock T, Nickles D, Kiessling M, Weit N, Breuer R, Müller W, Wabnitz G, Frey F, Nicolay JP, Booken N, Samstag Y, Klemke CD, Herling M, Boutros M, Krammer PH, Arnold R. A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes. Immunity. 2012 Oct 19;37(4):697-708.
  • Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M. The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2. Chem Biol. 2012 Sep 21;19(9):1093-104
  • Ding J, Polier G, Köhler R, Giaisi M, Krammer PH, Li-Weber M. Wogonin and related natural flavones overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein resistance of tumors by down-regulation of c-FLIP protein and up-regulation of TRAIL receptor 2 expression. J Biol Chem. 2012 Jan 2;287(1):641-9.
  • Kiessling MK, Oberholzer PA, Mondal C, Karpova MB, Zipser MC, Lin WM, Girardi M, Macconaill LE, Kehoe SM, Hatton C, French LE, Garraway LA, Polier G, Süss D, Klemke CD, Krammer PH, Gülow K, Dummer R. High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade. Blood. 2011 Feb 24;117(8):2433-40
  • Helmholtz Association: Helmholtz Alliance on Immunotherapy of Cancer. 2008 – 2013, 875.000 € for scientific Project
  • DFG: SFB/TRR77 liver cancer from molecular pathogenesis to targeted therapies. 2010 – 2014
  • Biotech Cluster Rhine Neckar: Development of an IL-4 inhibitor for the treatment of cancer. 2009 – 2011
  • Wilhelm Sander Stiftung:  Neue therapeutische Ansätze bei Sutanen T-Zell-Lymphomen (CTCL) 2013 - 2015
  • Jose Carreras Leukemia Foundation: Potential role of NRP1 as a tumor suppressor in NFkB dependent leukemias and lymphomas. 2010 – 2012
  • 1991 Kind Phillip Award for Leukemia Research
  • 1995 Behring Lecture
  • 1995 Robert Koch Prize
  • 1996 The German Cancer Prize
  • 1996 Kitasato-Behring Prize
  • 1996 Heinz-Ansmann-Prize
  • 1996 Meyenburg Prize
  • 1997 Cancer Research Award Wilhelm Warner Foundation
  • 1998 Avery-Landsteiner-Prize
  • 2000 Norman Heatley Lecture, Oxford
  • 2000 Ernst-Jung Prize for Medicine
  • 2000 Ludwik Hirszfeld Medal of the Polish Society for Experimental and Clinical Immunology
  • 2000 Theodor Kocher Lecture, Düsseldorf
  • 2001 Genius Biotech Award for APOGENIX
  • 2001 MRC Lecture, Society of Toxicology, San Francisco
  • 2003 Melchers Lecture Leipzig
  • 2003 Lautenschläger Research Prize
  • 2003 Member of Academia Europaea
  • 2004 1st International Cell Death Society Prize
  • 2004 Member of “Deutsche Akademie der Naturforscher Leopoldina”
  • 2005 Career Award of the European Cell Death Organization
  • 2006 Pels Center for Biochemistry and Structural Biology, Rockefeller University Lecture
  • 2009 Member of the “Heidelberger Akademie der Wissenschaften”
  • 2011 Founding Member of the European Academy for Tumor Immunology
  • 2011 Deutsche Krebshilfe (German Cancer Aid) Prize
  • 2011/2012 Johann-Georg-Zimmermann Medal