Ana Arpón Miranda
Laura Martinez Escardó
María Sánchez Osuna
Former lab members:
Elisenda Casanelles Abella
Irene Casanova Salas
Gisela Gabernet Garriga
Mercè Garcia Belinchon
Estel Gil Guiñon
Victoria Iglesias Guimarais
Jorge Urresti Ibáñez
1) To establish which chemical compounds are the most efficient inducing cell death in glioblastoma multiform cells (GBM) derived human cell lines and to determine which type of cell death is provoked.
2) To verify the existence of a main and common pathway among all the toxic drugs and to analyze the different components of this pathway to fix the major actors in both cell lines and primary tumors.
3) With the aim to study the therapeutic potential of the above described drugs, we will analyze the effect and the molecular mechanism involved in cell death induction in our primary cultures.
4) An in vitro study will be carried out to answer if there is a phagocytic and/or immune response stimulated by GBM cells that have been sensitive to different apoptotic stimuli.
MAIN RESEARCH LINES
Analysis of the mechanisms involved in the resistance against death receptor-triggered apoptosis in glioblastoma multiform cells.
The main goal of the project is based on the study of the molecular mechanisms involved, and not yet characterized, in the inherent resistance of glioblastoma multiform cells (GBM) from TRAIL-mediated cytotoxicity. The data obtained in different research laboratories are disappointing: most of GBM are resistant to TRAIL-triggered apoptosis needing the addition of an inhibitor of the macromolecular synthesis to become sensitive. For this reason, we will study the implication of the DISC endogenous inhibitors in the acquisition of this resistance, as well as the role that the anti-apoptotic members of Bcl-2’s family play in TRAIL-induced cell death. Moreover, we will approach the study of the relevance of the apoptotic nucleases in the regulation of TRAIL-mediated apoptotic cell death.
• Sánchez-Osuna M, Garcia-Belinchón M, Iglesias-Guimarais V, Gil-Guiñón E, Casanelles E, Yuste VJ. Caspase-activated DNase is necessary and sufficient for oligonucleosomal DNA breakdown, but not for chromatin disassembly during caspase-dependent apoptosis of LN-18 glioblastoma cells. J Biol Chem. 2014 289(27):18752-69.
• Iglesias-Guimarais V, Gil-Guiñon E, Sánchez-Osuna M, Casanelles E, García-Belinchón M, Comella JX, Yuste VJ. Chromatin collapse during caspase-dependent apoptotic cell death requires DNA fragmentation factor, 40-kDa subunit-/caspase-activated deoxyribonuclease-mediated 3'-OH single-strand DNA breaks. J Biol Chem. 2013 ;288(13):9200-15..
• Casanelles E, Gozzelino R, Marqués-Fernández F, Iglesias-Guimarais V, Garcia-Belinchón M, Sánchez-Osuna M, Solé C, Moubarak RS, Comella JX, Yuste VJ. NF-κB activation fails to protect cells to TNFα-induced apoptosis in the absence of Bcl-xL, but not Mcl-1, Bcl-2 or Bcl-w.
Biochim Biophys Acta. 2013 ;1833(5):1085-95.
• Iglesias-Guimarais V, Gil-Guiñon E, Gabernet G, García-Belinchón M, Sánchez-Osuna M, Casanelles E, Comella JX, Yuste VJ. Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease. J Biol Chem. 2012 ;287(10):7766-79.
• Dieker J, Iglesias-Guimarais V, Décossas M, Stevenin J, van der Vlag J, Yuste VJ, Muller S. Early Apoptotic Reorganization of Spliceosomal Proteins Involves Caspases, CAD and Rearrangement of NuMA.