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Sistema Inmunológico: Inflamación y apoptosis
Centro de Investigaciones Biomédicas de Aragón (CIBA)
patentes

 

Grupo coordinado por Julián Pardo Jimeno

Centro de Investigaciones Biomedicas de Aragon (CIBA
Universidad de Zaragoza.
Avda San Juan Bosco 13
50009 Zaragoza


Tel. +34876554338
E-mail: pardojim@unizar.es

 


Miembros del grupo

Dr. Luis Martínez-Lostao
Dra. María Pilar Jiménez de Bagües
Dra. Eva Ma Galvez Buerba
Dr. Diego de Miguel

Investigadores predoctorales

Paula Jaime
David Núñez
Diego Sánchez
Maykel Arias
Llipsy Santiago
Marta Pérez
Laura Comas
Miguel Martínezo

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Líneas de Investigación

  • - Inmunoterapia anti-tumoral basada en células NK.
  • - Mecanismos de muerte celular inducida por linfocitos T citóxicos y células NK.
  • - Papel del sistema de exocitosis granular (perforina/granzimas) en el control del desarrollo tumoral y de infecciones por patógenos intracelulares.
  • - Nuevas formulaciones de TRAIL para el tratamiento de tumores sólidos y hematológicos.
  • - Inflamación y autoinmunidad: Implicación de la granzima A y la granzima B en la patología inflamatoria infecciosa y autoinmune.
  • - Validación de nuevos biomarcadores para la infección oportunista Aspergilosis Invasiva.
  • - Apoptosis y tuberculosis: Relación entre la apoptosis y la respuesta inmune frente a M. tuberculosis.

 

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Publicaciones en relación con las líneas de Investigación (2009-2014)

  • Froelich, CJ., Pardo, J and Simon, MM. Granule-associated Serine Proteases: Granzymes might just not be killer proteases. 2009 Trends in Immunology, 30(3): 117-122.
  • Aguilo, JI., Garaude, J., Pardo, J., Villalba, M and Anel, A.: PKC-θ is required for NK cell activation and in vivo control of tumor progression. 2009, the Journal of Immunology, 182: 1972-1981.
  • Pardo, J., Aguilo, JI., Anel, A., Martin, P., Joeckel, L., Borner, C.., Wallich, R., Müllbacher, A., Froelich, CJ. and Simon, MM. The Biology of Cytotoxic Cell Granule exocytosis Pathway: granzymes have evolved to induce cell death and inflammation. 2009, Microbes and Infection, 11: 452-459.
  • Herz, J. (1), Pardo, J. (1), Kashkar, H., Schramm, M., Kuzmenkina, E., Bos, E., Wiegmann, K., Wallich, R., Peters, PJ., Herzig, S., Schmelzer, S., Krönke, M., Simon, MM and Utermöhlen, O. Acid sphingomyelinase is a critical regulator of cytotoxic granule secretion by primary T lymphocytes. 2009, Nature Immunology, 10:761-768.
  • Pardo, J. (Senior authorship), Metkar, SS., Menaa, C., Wang, B., Sánchez-Martínez, D., Wallich, R., Shi, L., Joeckel, L., Simon, MM. and Froelich, CJ. Non cytotoxic pro-inflammatory function of mouse and human gzmA, 2009, Proceedings of the 2nd European Conference in Immunology.
  • Pardo, J. (Senior authorship),, Gálvez, EM., Koskinen, A., Simon, MM., Lobigs, M., Regner, M and Müllbacher, A. Caspase-dependent inhibition of mousepox replication by gzmB. 2009. Plos One, 4(10): e7512
  • Pardo, J., Simon, MM. and Froelich, CJ. Letter to the editor : Granzyme A is a proinflammatory protease, 2009, Blood, 114: 3968.
  • Aguiló, JI., Anel, A., Catalán, E., Sebastián, A., Acín-Pérez, RA., Naval, J., Wallich, R., Simon, MM and Pardo, J. Granzyme B of cytotoxic T cells induces extramitochondrial reactive oxygen species production via caspase-dependent NADPH oxidase activation . Immunology and Cell Biology, 2010, 88(5):545-54.
  • Domingo, MP., Pardo, J., Cebolla, V and Galvez, EM. Berberine: a fluorescent alkaloid with a variety of applications from medicine to chemistry. Minireviews in Organic Chemistry, 2010, 7, 335-340.
  • Martin P, Pardo J, Schill N, Joeckel L, Berg M, Froelich CJ, Wallich R, Simon MM. Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics. The Journal of Biological Chemistry, 2010, 285(24):18918-27.
  • Charni, S., Bettignies, G., Rathore, MG., Aguiló, JI., van den Elsen, PJ., Haouzi, D., Hipskind, RA., Enriquez, JA., Sanchez-Beato, M., Pardo, J., Anel, A and Villalba, M. Oxidative Phosphorylation induces de novo expression of the Major Histocompatibility Complex-I in tumor cells through de ERK5 pathway. the Journal of Immunology, 2010, 185: 3498–3503.
  • Ivanova, S., Gregorc, U., Vidergar, N., Javier, R., Bredt, D.S., Vandenabeele, P., Pardo, J., Simon, MM., Turk, V., Banks, L. and Turk, B. MAGUKs, scaffolding proteins at cell junctions, are substrates of different proteases during apoptosis. Cell Death and Disease, 2011, Jan 20; 2:e116.
  • Gálvez, EM and Pardo, J. Quantum dot bioconjugates: emerging tools with great potential to study protein interactions and dynamics by fret. International Journal of Biomedical Nanoscience and Nanotechnology, 2011, 2(1), 55 - 74.
  • Joeckel, L., Walllich, R., Martin, P., Sanchez-Martinez, D., Weber, FE, Martin, SF., Borner, C., Pardo, J., Froelich, CJ. and Simon, MM. Murine granzyme K has pro-inflammatory potential. Cell Death Diff, 2011, 8(7):1112-9.
  • Jiménez de Bagüés MP, de Martino A, Quintana JF, Alcaraz A and Pardo J. Course of infection in immunocompromised mice with the emergent pathogen Brucella microti. Infection and Immunity, 2011, 79, 3934–3939.
  • Metkar, SS., Wang, B., Catalan, E., Anderluh, G., Gilbert, RJC., Pardo, J and Froelich, CJ. Perforin forms proteolipid pores: a possible gateway for granzyme delivery. PLOS One, 2011-10-17.
  • Ospina, A, Lagunas-Martínez, A, Pardo, J and Carrodeguas, JA. Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL. FEBS letters, 2011.
  • Catalán E, Sánchez-Martínez, D and Pardo J. GZMA (granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3). Atlas Genet Cytogenet Oncol Haematol. September. 2011.
  • Domingo M., Pardo J., Roc L., Palacian M., Colmenarejo C., Meis J., Peyman-Fard N., Revillo M., Galvez E., Rezusta A. Fast and sensitive detection of the mycotoxin gliotoxin and related compounds during human aspergillosis. Clinical Microbiology and Infection, 17, S4. 2011.
  • Domingo MP, Colmenarejo C, Martínez-Lostao L, Müllbacher A, Jarne C, Revillo MJ, Delgado P, Roc L, Jacques F. Meis, Antonio Rezusta, Julian Pardo* and Eva M Gálvez (shared senior authorship). Bis(methyl)Gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis. Diagnostic Microbiology and Infectious Disease, 2012, 73,(1), 57–64.
  • Rombach-Riegraff V, Oswald P, Bienert R, Petersen J, Domingo MP, Pardo J, Gräber P, Galvez EM. Blinking effect and the use of quantum dots in single molecule spectroscopy. Biochem Biophys Res Commun, Nov 15. 2012.
  • Aguiló JI, Iturralde M, Monleón I, Iñarrea P, Pardo J, Martínez-Lorenzo MJ, Anel A, Alava MA. Cytotoxicity of quinone drugs on highly proliferative human leukemia T cells: Reactive oxygen species generation and inactive shortened SOD1 isoform implications. Chem Biol Interact, 98(1-3):18-28. 2012.
  • Anel A, Aguiló JI, Catalán E, Garaud, J, Rathor, MG, Pardo J and Villalba M. Protein Kinase C-theta (PKC-theta) in Natural Killer (NK) cell function and anti-tumor immunity. Frontiers in Immunology. 2012.
  • Aporta, A Arbue, A, Aguilo JI, Monzon M, Badiola JJ, de Martino A, Ferrer N, Marinova D, Anel A, Martin C and Pardo J. Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death. PLOS One 7(9), e45213. 2012.
  • Grasa-Lopez L, Murillo MD, Alcalde AI, Pardo J, Latorre E, Mesonero JE, Arruebo MP, Plaza MA and Gonzalo S. Role of TLR2 and TLR4 in serotonin-induced responses in mouse ileum and colon. Neurogastroenterology and Motility, 24, Sup 2. 2012.

  • 26. Ochoa MC, Fioravanti J, Rodriguez I, Hervas-Stubbs S, Azpilikueta A, Mazzolini G, Gurpide A, Prieto J, Pardo J, Berraondo P*, Melero I* (shared senior authorship). Antitumor immunotherapeutic and toxic properties of an HDL-conjugated chimeric IL-15 fusion protein. Cancer Res, 73(1); 139–49. 2012.
  • Martinez-Lostao, L, Anel, A, Regner, M and Froelich, CJ and Pardo, J. Immunological Cytotoxic Factors (Version 3.0). The Encyclopedia of Life Sciences. John Wiley & Sons, Ltd. 2013. http://www.mrw.interscience.wiley.com/emrw/047001590X/home/
  • De Miguel, D; Basanez, G; Sánchez, D; Galán-Malo, P; Marzo, I; Larrad, L; Naval, J; Pardo, J; Anel, A*; Martinez-Lostao, L* (shared senior authorship). Liposomes decorated with apo2l/trail overcome chemoresistance of human hematologic tumor cells. Molecular Pharmaceutics. 2013. 10, 893-904.
  • E. M. Galvez, M. Perez, P. Domingo, D. Nuñez, V. L. Cebolla, M. Matt and J. Pardo. Pharmacological/Biological Effects of Berberine. K.G. Ramawat, J.M. Merillon (eds.), Handbook of Natural Products, Springer-Verlag Berlin Heidelberg 2013.
  • A Morales, E Catalan, S Hervas, A Palazon, A Azpilikueta, E Bolaños, A, Anel, J Pardo* and I Melero*(shared senior authorship). Essential complicity of perf/granzyme and FAS-L mechanisms to achieve tumor rejection after treatment with anti-CD137 mAb. J ImmunoTher of Cancer. 2013, 1:3
  • D Núñez, MP Domingo, D Sánchez-Martínez, V Cebolla, A Chiou, A Velázquez-Campoy, J Pardo* and EM Gálvez* (shared senior authorship). Recombinant production of human ICAM-1 chimeras by single step on column refolding and purification . Process in Biochemistry 2013, 48:708-715
  • Aguilo JI, Alonso H, Uranga S, Marinova D, Arbués A, de Martino A, Anel A, Monzon M, Badiola J, Pardo J, Brosch R, Martin C. ESX-1-induced apoptosis is involved in cell-to-cell spread of Mycobacterium tuberculosis. Cell Microbiol. 2013 Dec;15(12):1994-2005
  • Zorn, CN*, Pardo, J* (similar contribution), Martin, P, Kuhny, M, Simon, MM and Huber, M. Secretory lysosomes of mouse mast cells store and exocytose active caspase-3 in a strictly granzyme B dependent manner. Eur J Immunol 2013 Dec;43(12):3209-18.
  • Aguilo JI, Marinova D, Martin C. and Pardo J. ESX-1-induced apoptosis during mycobacterial infection: to be or not to be, that is the question. Frontiers in Cellular and Infection Microbiology, 2013, 3:88.
  • Aporta A, Catalán E, Galán-Malo P, Ramírez-Labrada A, Pérez M, Azaceta G, Palomera L, Naval J, Marzo I, Pardo J* and Anel A* (Shared senior authorship). Granulysin induces apoptotic cell death and cleavage of the autophagy regulator Atg5 in human hematological tumors. Biochemical Pharmacology 2014 87: 410-423.
  • Wua, SH, Núnez, D, Hua, SY, Domingoc, MP, Chenf, YC, Wei, PK, Pardo, J*, Gálvez, EM*, Chiou, A* (Shared senior authorship). The effect of acidic pH on the inhibitory efficacy of peptides against the interaction ICAM-1/LFA-1 studied by surface plasmon resonance (SPR). Biosensors and Bioelectronics 2014. 15, 159-166.
  • Jiménez de Bagüés,MP, Iturralde,M, Arias, MA, Pardo, J, Cloeckaert, A and Zygmunt, MS. The New Strains Brucella inopinata BO1 and Brucella spp. 83-210 Behave Biologically Like Classical Infectious Brucella spp. and Caus
  • Sanchez, D, Krzywinska, E, Rathore, MG, Saumet, A, Cornillon, A, Lopez-Royuela, N, Martínez-Lostao, L, Ramirez-Labrada, A, Lu, ZY, Rossi, JF, Fernández-Orth, D, Escorza, S, Anel, A, Lecellier, C.H., Pardo, J* and Villalba, M* (Shared senior authorship). All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity, 2014, 49, 42-52.
  • Ebru Karpuzoglu, Chad W. Schmiedt, Julian Pardo, Megan Hansen, Tai L. Guo , Steven D. Holladay, Robert M. Gogal Jr. Serine protease inhibition attenuates estrogen-mediated rIL12-induced GZMA activity and proinflammatory biomolecules by modulating Th2 profile. Endocrinology 2014, Accepted.

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Proyectos (vigentes en 2014)

  • - Role of cell death and inflammation during tumor development, pathogen infection and autoimmune disorders: novel functions of the granule exocytosis pathway of cytotoxic cells.
    Ministerio de Ciencia e Innovación.
    IP: Julián Pardo
  • - “Kit ELISA to detect bmGT during invasive aspergilosis”, BDR SL, 2013, 30.000 euro, PI: J Pardo
  • - Hello-kit. Desarrollo de un kit universal para liberación remota controlada de fármacos mediante hipertermia magnética en aplicaciones oncológicas
    Ministerio de Economía y Competitividad. Programa Innpacto 2012.
    IP: NanoScale, Nico Cassinelli
    Número de investigadores participantes: 13
  • - Interacción del metabolismo y la inmunoterapia: una aproximación clínica
    Entidad financiadora: CTTP (Comunidad de Trabajo de los Pirineos), Gobierno de Aragón
    Entidades participantes: Universidad de Zaragoza
    Duración, desde: 2013 hasta: 2014 Cuantía de la subvención: 24.550 euro
    Investigador responsable: Alberto Anel
    Número de investigadores participantes: 8
  • - Título del proyecto: Liposomas recubiertos con el dominio extracelular de Apo2L/TRAIL como nuevo tratamiento anti-tumoral.
    Entidad financiadora: Fundación Eugenio Rodríguez Pascual (Referencia SO-0239).
    Cuantía de la subvención:: 15.400 €.
    Duración 2013.
    Investigador responsable: Luis Martinez Lostao.
    Número de investigadores participantes: 10
  • -Título del proyecto: Implicación de la inflamación inducida por la serinproteasa granzima A en la generación, progresión y pronóstico del cáncer colorrectal
    Entidad financiadora: Sociedad Aragonesa de Patología Digestiva
    Entidades participantes: Universidad de Zaragoza, Hospital Clinico universitario Lozano Blesa
    Duración desde: 2013 hasta: 2014 Cuantía de la subvención: 6000 euro
    Investigador responsable: Angel Ferrández
    Número de investigadores participantes: 6

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Tesis Doctorales

  • Elena Catalán.
  • Pablo Paz.
  • Adriana Aporta

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Patentes

  1. Inhibition of gliotoxin. J Pardo and MM Simon. PCT/EP2007/004023; 08/05/2006;
    Compañía que la explota: Max-Planck Innovation/Lead Discover Center (LDC).
  2. Using dimethyl gliotoxin ss' as diagnostic marker for fungal pathologies. MP, Domingo, EM Galvez, J Pardo. PCT/EP2012/058247. 04/05/2011. Compañía que la explota: BDR SL.
  3. Use of granulysin for the treatment of solid tumours. A Aporta, J Pardo, L Martinez-Lostao, B Conde and A Anel. P201330136, 06/02/2013.

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