SUMMARY OF RESEARCH

Our current research interest is in signal transduction and signaling molecules as drug targets with special emphasis on the role of tyrosine phosphorylation in protein/protein interactions and transmission of activating signals into the cells by redox mechanisms. In our laboratory we have focus our interest on the early signaling events triggered by CD38 or CD3 engagement in T cells from patients and mice with autoimmune diseases. Our focus is to understand how these molecules are associated with other cell surface receptors, intracellular protein tyrosine kinases (PTKs), or other signaling molecules. Our background is in cell signaling is now addressed with a more integrated view of the different signaling pathways and the incorporation of the new technologies that allow multiple measurements per sample (multiplex immunoassays, protein microarrays). Our group has given new insights to the role of CD38 in T cell signaling. We first described that CD38 is located in lipid rafts and dissected the main signaling transduction pathways involved upon CD38 engagement (J. Biol. Chem. 2002 and 2003). Now we have found that T cells from pacients with Lupus express relatively high amounts of CD38 on their surface with an abnormal proportion located in raft microdomains (Mol. Immunol. 2006). Moreover, in T cells CD38 translocates to the immunological synapse upon encounter with antigen-pulsed APCs (Blood, 2008), which adds new insights to the immunomodulatory role of CD38 in T cell responses. These two findings will be connected in ongoing projects, in particular to study the role of CD38 in the survival of SLE T cells and in healthy controls. We have also published a paper in Proteomics (2006), regarding the differential expression of haptoglobins in patients with SLE, which could explain some of the clinical manifestations of the disease related with oxidative stress and the risk of cardiovascular disease. We are now able to perform microarray-based technology to identify proteins preferentially expressed upon stimulation of peripheral blood mononuclear cells with REP sequences, whose potential postranslational modifications could have adversely impact on immune function. In summary we are using several approaches including proteomics, transfection experiments in heterologous systems, two-hybrid system, reporter gene systems, the use of transgenic animals, confocal and deconvolution microscopy and more recently, RNA interference technology and real time PCR. Our Institute has the equipment, personnel and animal facilities necessary to perform these techniques. CSIC as a whole provides technical assistance with core expensive equipment throughout the country if required.
Scientific adscription according with UNESCO: Inmunology: 2412.99 (Molecular Immunology). Cellular Biology: 2407.01; 2407.99 (Signal Transduction).

FUNDING AGENCIES LAST 5 YEARS

- BIOMARCADORES PROTEOMICOS EN CELULAS PERITONEALES Y VESICULAS EXTRACELULARES CIRCULANTES EN LUPUS: ALTERACIONES DEL ACETILOMA Y DEL FOSFOPROTEOMA EN AUSENCIA DE CD38. PROYECTO, PN2017 - PROY I+D+I - PRG. RETOS DE LA SOCIEDAD, Ref: SAF2017-89801-R, (2018 - 2021).

PUBLICATIONS LAST 5 YEARS

-Colomé, N.; Abian, J.; Aloria, K.; Arizmendi, J.M.; Barceló-Batllori S.; Braga-Lagache, S.; Burlet-Schiltz, O.; Carrascal, M.; Casal, J.I.; Chicano-Gálvez, E.; Chiva, C.; Clemente, L.F.; Elortza, F.; Estanyol, J.M.; Fernandez-Irigoyen, J.; Fernández-Puente, P.; Fidalgo, M.J.; Froment, C.; Fuentes, M.; Fuentes-Almagro, C.; Gay, M.; Hainard, A.; Heller, M,; Hernández, M.L.; Ibarrola, N.; Iloro, I.; Kieselbach, T.; Lario, A.; Locard-Paulet, M.; Marina-Ramírez, A,; Martín, L.; Morato-López, E.; Muñoz, J.; Navajas, R.; Odena, M.A.; Odriozola, L.; de Oliveira, E.; Paradela, A.; Pasquarello, C.; de Los Rios, V.; Ruiz-Romero, C.; Sabidó, E.; Sánchez Del Pino, M.; Sancho, J.; Santamaría, E.; Schaeffer-Reiss, C.; Schneider, J; de la Torre, C.; Valero, M.L.; Vilaseca, M.; Wu, S.; Wu, L.; Ximénez de Embún, P.; Canals, F.; Corrales, F.J., Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis, Journal of Proteomics, 2022, Vol. 251: 104409-104409, ARTÍCULO, Id:863133

-Martínez-Blanco, A.; Domínguez-Pantoja, M.; Botía-Sánchez, M.; Pérez-Cabrera, S.; Bello-Iglesias, N.; Carrillo-Rodríguez, P.; Martin-Morales, N.; Lario-Simón, A.; Pérez-Sánchez-Cañete, M.M.; Montosa-Hidalgo, L.; Guerrero-Fernández, S.; Longobardo-Polanco, V.M.; Redondo-Sánchez, S.; Cornet-Gomez, A.; Torres-Sáez, M.; Fernández-Ibáñez, A.; Terrón-Camero, L.; Andrés-León, E.; O¿Valle, F.; Merino, R.; Zubiaur, M.; Sancho, J., CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism, Frontiers in Immunology, 2021, Vol. 12: 713697, ARTÍCULO, Id:854129

-Mancera-Arteu, M.; Giménez, E.; Sancho, J.; Sanz-Nebot, V., Alterations in the Glycan Profile of Mouse Transferrin: New Insights in Collagen-Induced Arthritis, Journal of Proteome Research, 2020, Vol. 19: 1750-1759, ARTÍCULO, Id:805882

-Burlock, B.; Richardson, G.; García-Rodríguez, S.; Guerrero, S.; Zubiaur, M.; Sancho, J., The role of CD38 on the function of regulatory B cells in a murine model of lupus, International Journal of Molecular Sciences, 2018, Vol. 19: 10-2906, ARTÍCULO, Id:728661

-Sonia García-Rodríguez; Antonio Rosal-Vela; Davide Botta; Luz M. Cumba Garcia; Esther Zumaquero; Verónica Prados-Maniviesa; Daniela Cerezo-Wallis; Nicola Lo Buono; José-Ángel Robles-Guirado; Salvador Guerrero; Elena González-Paredes; Eduardo Andrés-León; Ángel Corbí; Matthias Mack; Friedrich Koch-Nolte; Ramón Merino; Mercedes Zubiaur; Frances E. Lund; Jaime Sancho, CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism, Scientific Reports, 2018, Vol. 8: 1-3357, ARTÍCULO, Id:702643

-Alberto Barroso; E. Giménez; A.Konijnenberg; Jaime Sancho; Victoria Sanz-Nebot; F. Sobott, Evaluation of ion mobility for the separation of glycoconjugate isomers due to different types of sialic acid linkage, at the intact glycoprotein, glycopeptide and glycan level, Journal of Proteomics, 2018, Vol. 173: 22-31, ARTÍCULO, Id:688367

DOCTORAL THESES LAST 5 YEARS