UMR 848

Director
Guido Kroemer
Phone : 33 1 42 11 60 46
Fax : 33 1 42 11 60 47
kroemer@orange.fr

Secretariat
Christelle Robin
christelle.robin@igr.fr

Research pavilion 1 (+3)

UMR 848 Apoptosis, cancer and immunity

Research unit

INSERM - IGR - Paris-XI University

Integrated Research Cancer Institute in Villejuif

Director : Dr Guido Kroemer

Work and objectives
Press Releases
Publications
Collaborations
Teaching activities

Organigramme

Work and objectives

Chemotherapy is commonly believed to kill cancer cells by apoptosis, a cell death modality that has been extensively studied over the last decades. Apoptotic cells exhibit a particular morphology (with chromatin condensation as the hallmark), accompanied by typical biochemical changes (such as caspase activation). Apoptosis is generally considered as a non-immunogenic cell death modality.

Recent work suggests that anticancer treatments also trigger other, non-apoptotic cell death modalities (autophagy, necrosis, mitotic catastrophe). Moreover, tumor cell death often occurs in an immunogenic fashion. The anticancer immune response elicited by dying tumor cells may dictate therapeutic success.

Based on these premises, it will be important to construct assay systems that detect non-apoptotic cell death modalities, to distinguish them mechanistically from apoptosis, and to understand which molecular features render some types of cell death immunogenic. We will perform a systematic study of the catabolic pathways induced by chemotherapeutic agents and ionizing radiation (by a metabolomics approach), construct videomicroscopic assays for the automated detection and quantification of several cell death modalities (by generating cells transfected with biosensors for apoptosis, autophagy, necrosis, mitotic catastrophe etc.), identify genes (by siRNA screenings) and agents (within compound libraries) that affect distinct cell death subroutines, and define the specific characteristics of immunogenic cancer cell death.

This knowledge will be validated in preclinical models of anticancer treatment, and will be applied to the analysis of samples from cancer patients. The in-depth exploration of the relationship between cell death mechanisms, resistance against cell death induction, and the interplay between the immune system and tumor cell death, should lay the theoretical foundation for an improved diagnostic, prognostic, predictive and therapeutic management of cancer.

Press Releases

December 27th 2007 : Inhibiting the Chekpoint kinase 1 protein leads to the death of tetraploid tumor cells
November 30th 2007 : Research on the march : Identifying 2 new uses for the Apaf-1 protein in oncology

Publications

RIP Kinases Initiate Programmed Necrosis. Galluzzi L, Kepp O, Kroemer G. J Mol Cell Biol. 2009 Aug 13. [Epub ahead of print]
The dendritic cell-like functions of IFN-producing killer dendritic cells reside in the CD11b+ subset and are licensed by tumor cells. Terme M, Mignot G, Ullrich E, Bonmort M, Minard-Colin V, Jacquet A, Schultze JL, Kroemer G, Leclerc C, Chaput N, Zitvogel L. Cancer Res. 2009 Aug 15;69(16):6590-7.
DRAM: a phylogenetically ancient regulator of autophagy. Criollo A, Dessen P, Kroemer G. Cell Cycle. 2009 Aug;8(15):2319-20.
Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects. Zitvogel L, Kroemer G. J Clin Invest. 2009 Aug;119(8):2127-30
Mitochondrial membrane permeabilization in neuronal injury. Galluzzi L, Blomgren K, Kroemer G. Nat Rev Neurosci. 2009 Jul;10(7):481-94.
Targeting mitochondrial apoptosis by betulinic acid in human cancers. Fulda S, Kroemer G. Drug Discov Today. 2009 Jun 9.
Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis. Fortunato F, Kroemer G. Autophagy. 2009 Aug;5(6):850-3.
Nutlin kills cancer cells via mitochondrial p53. Morselli E, Galluzzi L, Kepp O, Kroemer G. Cell Cycle. 2009 Jun 1;8(11):1647-8.
Cytoplasmic functions of the tumour suppressor p53. Green DR, Kroemer G. Nature. 2009 Apr 30;458(7242):1127-30.
Suppression of the DNA damage response in acute myeloid leukemia versus myelodysplastic syndrome. Boehrer S, Adès L, Tajeddine N, Hofmann WK, Kriener S, Bug G, Ottmann OG, Ruthardt M, Galluzzi L, Fouassier C, Tailler M, Olaussen KA, Gardin C, Eclache V, de Botton S, Thepot S, Fenaux P, Kroemer G. Oncogene. 2009 Jun 4;28(22):2205-18.

See also : publications list 2008-2009

Collaborations

EU grant "Apoptosis mechanisms" 1999-2003
Klaus-Michael Debatin (University of Ulm, Germany)
Gerry Melino (University of Rome Tor Vergata, Rome, Italy)
Mauro Piacentini (Istituto Nazionale delle Malattie Infettive, Rome, Italy)
EU grant "Impaled": 2002-2005
Boris Zhivotovsky (Karolinska Hospital, Stockholm, Sweden)
EU grant "Right": 2005-
Annick Harel-Belan (IRSC, Villejuif, France)
Thomas Rudel (Charité Hospital, Berlin, Germany)
Massimo Zervian (Max Planck Institute, Dresden, Germany)
EU grant "Active p53": 2005-
Moshe Oren (Weizman Institute, Rehovot, Israel)
EU grant "Trans-Death": 2005-
Marja Jaattela (Danish Cancer Institute, Kopenhagen, Denmark)
Roberto Testi (University of Rome Tor Vergata, Rome, Italy)
Cancéropôle Ile de France: 2005-
Pierre Fenaux (Hopital Avicennes, Bobigny, France)
Alain Israel (Institut Pasteur, Paris, France)
Vincent Ribrag (Institut Gustave Roussy, France)
Contrat Interface INSERM 2003-
Jean-Charles Soria (Institut Gustave Roussy, France)
Laurence Zitvogel (Institut Gustave Roussy, France)
Agence Nationale pour la Recherche sur le SIDA 2000-
Bernard Roques (Université de Paris VI, France)
Institut Nationale du Cancer (INCa): 2006-
Matthew Albert (Pasteur Institute, Paris, France)
Sebastian Amigorena (Insitut Curie, INSERM, Paris, France)
Joint French-Chilean Reserch Projects
Sergio Lavandero (University of Santiago, Santiago de Chile, Chile)

Teaching activities

University of Innsbruck, Faculty of Medicine, Austria (1984)
Autonomous University of Madrid, Faculty of Sciences, Spain (1991)
University of Lyon, Faculty of Medicine, France (1996)
University of Paris Sud, Faculty of Sciences, France (1995-1997)
University of Paris René Descartes-Necker Hospital, France (1996)
University of Versailles-Saint Quentin, Faculty of Sciences, France (1995-1997)
University of Zaragoza, Faculty of Sciences, Spain (1997)
University of Paris VII Denis Didérot, Faculty of Medicine, France (1997-2002)
University of Strasbourg, France (1998)
University of Nice Sophia Antipolis, France (1998)
University of Paris VI, France (1999)
University of Paris IX, France (2001-2002)
University of Rome Tor Vergata, Italy (2003)
University of Paris XI, France (2005)

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