Líneas de investigación
Nuestra investigación se centra en los mecanismos moleculares que permiten el aprendizaje, la formación de nuevos recuerdos y otras modificaciones duraderas del comportamiento animal. En concreto, investigamos el papel de determinados factores de transcripción y epigenéticos en esos procesos. También investigamos cómo el mal funcionamiento de estos mecanismos puede dar lugar a patologías del sistema nervioso. Para abordar esas cuestiones usamos una aproximación multidisciplinar que combina estudios de genética, genómica, biología molecular y celular, electrofisiología y conducta animal. Desde el punto de vista metodológico, estamos particularmente interesados en la aplicación de las nuevas tecnologías de edición epigenética y perfilado genómico en el sistema nervioso.
Nuestra investigación actual se centra en las siguientes dos áreas:
• Regulación de la expresión génica dependiente de actividad por mecanismos epigenéticos y transcripcionales: Los modelos celulares actuales para explicar cómo se forman las memorias proponen que los recuerdos están codificados en forma de cambios en la fuerza de conexiones sinápticas específicas. Estos cambios requieren a su vez de cambios en la expresión génica de las neuronas. En el laboratorio, estamos interesados en explorar el papel que juegan en este proceso algunos factores de transcripción regulados por actividad (como CREB y SRF), algunas enzimas epigenéticas (como CBP y p300), y la modificación covalente de histonas y la metilación del DNA.
• Contribución de mecanismos epigenéticos a la patoetiología de la discapacidad intelectual: Investigamos la relación entre fallos en los mecanismos de regulación epigenética y diversos trastornos neurológicos asociados a problemas cognitivos que son hoy en día incurables, tales como el síndrome de Rubinstein-Taybi y la discapacidad intelectual asociada al cromosoma X. Para ello, generamos y caracterizamos modelos murinos de estos trastornos, investigamos las causas moleculares que subyacen a los síntomas y ensayamos nuevas terapias.
Publicaciones relevantes
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Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.
Del Blanco B, Niñerola S, Martín-González AM, Paraíso-Luna J, Kim M, Muñoz-Viana R, Racovac C, Sánchez-Mut JV, Ruan Y and Barco A.
Nature Communications.
2024
15, 1781 (2024)
https://www.nature.com/articles/s41467-024-45773-3
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Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding
Fernández-Nogales, M., López-Cascales, M.T., Murcia-Belmonte, V., Escalante, A., Fernández-Albert, J., Muñoz-Viana, R., Barco, A., Herrera, E.
Advanced Science
2022
9 (29): art. 2200615
https://doi.org/10.1002/advs.202200615
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CBP is required for establishing adaptive gene programs in the adult mouse brain.
Lipinski, M.#, Niñerola, S#., Fuentes-Ramos, M., Valor, L.M., del Blanco, B., López-Atalaya, J.P., Barco, A.
J Neurosci.
2022
42(42): 7984-8001
https://doi.org/10.1523/JNEUROSCI.0970-22.2022
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CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages.
González-Martínez, R., Márquez-Galera, A., Del Blanco, B., López-Atalaya, J.P., Barco, A., Herrera, E.
Cells
2022
11(24): 4118
https://doi.org/10.3390/cells11244118
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Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Rabaneda LG, García-Lira C, Grand T, Briz V, Velasco ER, Andero R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I
eLife
2021
10:e71575
https://doi.org/10.7554/eLife.71575
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Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis
Cid E, Marquez-Galera A, Valero M, Gal B, Medeiros DC, Navarron CM, Ballesteros-Esteban L, Reig-Viader R, Morales AV, Fernandez-Lamo I, Gomez-Dominguez D, Sato M, Hayashi Y, Bayés À, Barco A, Lopez-Atalaya JP, de la Prida LM
Cell Rep
2021
35(10):109229
https://doi.org/10.1016/j.celrep.2021.109229
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KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain
Lipinski M, Muñoz-Viana R, Del Blanco B, Marquez-Galera A, Medrano-Relinque J, Caramés JM, Szczepankiewicz AA, Fernandez-Albert J, Navarrón CM, Olivares R, Wilczyński GM, Canals S, Lopez-Atalaya JP, Barco A
Nat Commun
2020
11(1):2588
https://doi.org/10.1038/s41467-020-16246-0
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CBP and SRF co-regulate dendritic growth and synaptic maturation
Del Blanco B, Guiretti D, Tomasoni R, Lopez-Cascales MT, Muñoz-Viana R, Lipinski M, Scandaglia M, Coca Y, Olivares R, Valor LM, Herrera E, Barco A
Cell Death & Differentiation
2019
26(11):2208
https://doi.org/10.1038/s41418-019-0285-x
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CBP/p300 in brain development and plasticity: disentangling the KAT’s cradle
Lipinski M, Del Blanco B, Barco A
Current Opinion in Neurobiology
2019
59:1
https://doi.org/10.1016/j.conb.2019.01.023
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Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models
Hutson TH, Kathe C, Palmisano I, Bartholdi K, Hervera A, De Virgiliis F, McLachlan E, Zhou L, Kong G, Barraud Q, Danzi MC, Medrano-Fernandez A, Lopez-Atalaya JP, Boutillier AL, Sinha SH, Singh AK, Chaturbedy P, Moon LDF, Kundu TK, Bixby JL, Lemmon VP, Barco A, Courtine G, Di Giovanni S
Sci Transl Med
2019
11(487):eaaw2064
https://doi.org/10.1126/scitranslmed.aaw2064
Financiación actual:
Nuestra investigación se financia gracias al apoyo de distintas organizaciones, públicas y privadas, nacionales e internacionales. En la actualidad recibimos fondos del MINECO, la Generalitat Valenciana, la Fundación Alicia Koplowitz, y la fundación americana Brain & Behavior Research Foundation.
Financiación previa por parte de las siguientes instituciones y programas:
Alumni, visitors and former members:
- Samanta Ortuño graduada en Biotecnología en la Universidad Miguel Hernández de Elche (UMH), con los Másteres en Biotecnología y Bioingeniería (UMH) y en Bioinformática (Universidad de Murcia). Realizó el trabajo de fin de Grado y Máster en biología molecular en el laboratorio del Dr. Antonio Vera (UMH). Continuó su experiencia trabajando en Metabarcoding y Bioinformática en la empresa Taxon Estudios Ambientales S.L. y en el laboratorio del Dr. José Antonio García Charton (Universidad de Murcia).
- Ana Martín estudió Biología en la Universidad de Málaga. Gracias al apoyo de una beca internacional de doctorado Marie Curie fellowship, Ana está desarrollando su proyecto de doctorado en el marco de una colaboracion entre el grupo del Prof. Wilczynski en el Nencki Institute of Experimental Biology (Varsovia) y nuestro laboratorio.
- Mayte López Cascales es licenciada en Bioquímica por la Universidad de Murcia, con un Máster de Neurociencias por la Universidad Pablo de Olavide de Sevilla, y Máster de Bioinformática en la Universidad de Murcia. En 2014 recibió el premio al mejor trabajo fin de master de bioinformatica por la universidad de Murcia. Actualmente está realizando su tesis doctoral en el grupo de la Dra. Herrera y trabaja en varios proyectos colaborativos entre los dos laboratorios.
- Jordi Fernández studied Biology at the Universitat de Girona (UdG) and got his Interuniversity Master degree in Neuroscience coordinated by the Universitat de Barcelona (UB). He was first trained in neurosciences and in molecular and cell biology techniques in the laboratories of Dr. Gemma Huguet (School of Science, UdG), Dr. Carles Sindreu (School of Medicine, UB) in which he conducted his master thesis, and Dr. Manuel Irimia (Centre de Regulació Genòmica, CRG). He joined our group in February 2015 thanks to a fellowship awarded by the Severo Ochoa program (MINECO). He defended his Ph.D. thesis in October 2019 and obtained the maximal qualification. Thesis: Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus. Publications with us: Fernandez-Albert et al., Nat Neurosci 22, 1718-30; Lipinski et al., Nat Comm 11(1):2588. Other positions: Lab. Dr. Mark Schnitzer. University of Stanford, San Francisco, San Francisco, USA.
- Michal Lipinski estudió Biotecnología en la Universidad de Varsovia de Ciencias de la Vida (Polonia) y ha realizado estancias en laboratorios del Instituto Nencki de Biología Experimental (Varsovia) y del Departamento de Anatomía de la Universidad de Zurich. En Junio del 2012 se incorporó a nuestro grupo para realizar su tesis doctoral gracias a una beca financiada por el programa de Becas Santiago Grisolia de la Generalitat Valenciana. He defended his Ph.D. thesis in December 2019 and obtained the maximal qualification. Thesis: Role of CBP and p300 in the establishment and maintenance of transcriptional programs in adult excitatory neurons. Publications with us: Ito et al., Nat Comm 5:4450; Galvao-Ferreira et al., eNeuro 4(2); Scandaglia et al. Cell Reports 21(1):47-59; del Blanco et al., Cell Death Differ 26(11):2208-2222; Lipinski et al., Curr Opin Neurobiol 59:1-8;Fernandez-Albert et al., Nat Neurosci 22, 1718-30; Lipinski et al., Nat Comm 11(1):2588. Other positions: Lab. Dr. Paola Arlotta & Aviv Regev. Harvard Department of Stem Cell and Regenerative Biology, Cambridge & BROAD Institute. MA, USA.
- Marilyn Scandaglia studied Molecular Biotechnology at the Università Alma Mater Studiorum di Bologna in Italy. In 2011, as a pregraduate student, she moved to the Instituto de Neurociencias de Alicante and joined our lab to carry out her Master and PhD theses. She defended her Ph.D. thesis in January 2018 and obtained the maximal qualification. She also received the special distinction (Premio Extraordinario). Thesis: Role of lysine demethylase 5C in neurodevelopment and intellectual disability. Publications with us: Fiorenza et al., Cereb Cortex 26(4):1619-33; Scandaglia et al., Sci Reports5:17470; Iwase et al., J Neurosci 37(45):10773-10782; Scandaglia et al. Cell Reports 21(1):47-59; del Blanco et al., Cell Death Differ 26(11):2208-2222; Scandaglia and Barco. J Med Gen 56(8):491-498. Other positions: Lab. Dr. Berta Lopez Sanchez-Laorden. Instituto de Neurociencias (UMH-CSIC), Alicante, Spain.
- Anna Fiorenza studied Biology at the Università degli studi del Sannio in Italy. In 2008, she moved to the Instituto de Neurociencias de Alicante, as part of the «Erasmus Placement» subprogram in the U.E. Lifelong Learning Programme, where she worked in the lab of Dr. Lerma in the physiology of kainate receptors. In 2010, she was awarded a fellowship from the INA-Consolider Program and decided to join our group to carry out her thesis. She defended her Ph.D. thesis in September 2015 and obtained the maximal qualification. Thesis: Regulation of neuronal plasticity and responsiveness by the microRNA system. Publications with us: Fiorenza et al., Cereb Cortex 26(4):1619-33; Scandaglia et al., Sci Reports5:17470; Fiorenza & Barco, Neurobiol Learn Mem May 135:3-12. Other positions: Lab. Dr. Dorit Ron. University of California, San Francisco, San Francisco, USA; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, USA.
- Deisy Guiretti studied Biology at the National University of Misiones, Argentina. She later investigated in the field of viral variability and phylogenia at the National Institute of Cancer in Rio de Janeiro and in the University of Edinburgh. She joined our lab in 2009 to carry out her thesis working on the etiology of Huntington’s disease. She defended her Ph.D. thesis in September 2015 and obtained the maximal qualification. Thesis: Lysine deacetylation and transcriptional dysregulation in neurological disorders: Huntington’s disease and the Rubinstein-Taiby syndrome. Publications with us: Valor et al., J Neurosci 33(25):10471-82; Guiretti D and Valor LM, Neuropharmacology 80:103-114; Guiretti et al., Neurobiol Dis 89:190-201; Hervas-Corpion et al., Sci Rep 8(1):9925; del Blanco et al., Cell Death Differ 26(11):2208-2222.
- Jose Viosca got his Master degree in Biochemistry in the Universidad de Valencia. He worked with us from October 2005 to May 2010 investigating the role of CREB and neuronal chromatin acetylation in learning and memory. He defended his Ph.D. thesis in May 2012 and obtained the maximal qualification. He also received the special distinction (Premio Extraordinario). He later moved to the laboratory of Cornelius Gross in EMBL-Monterotondo (Italy) for his first postdoctoral stay. Thesis: Common molecules in memory formation and congenital intellectual disability: a role for the Ras-ERK-CREB pathway in cognition. Publications with us: Viosca et al., J Neurosci 27(47): 12761; Viosca et al. Learn Mem16(3): 193; Viosca et al. Learn Mem 16(3): 198; Viosca et al. Genes Brain Behav 8(1):60; Viosca et al. Neurobiol Dis 37(1):186; Lopez-Atalaya et al. EMBO J 30(20):4287; Valor et al. Curr Pharm Des 19(28):5051-64. Other positions: Lab. Dr. Cornelius Gross. EMBL Monterotondo. Monterotondo, Italy.
- Eva Benito-Garagorri studied Biochemistry at the University of the Basque Country. She carried out her PhD in our laboratory working on the transcriptional response to neuronal activity and defended her Ph.D. thesis in June 2011, obtaining the maximal qualification. She is currently a postdoc at the laboratory of Andre Fischer in ENI-Gottingen (Germany). Thesis: A comparative transcriptomics approach for unveiling gene expression networks of activity-driven neuronal stimulation and plasticity. Publications with us: Viosca et al., J Neurosci 27(47): 12761; Viosca et al., Learn Mem 16(3): 198; Benito and Barco, Trends Neurosci 33(5): 230; Benito et al., J Neurosci 31(50): 18237; Gruart et al., J Neurosci 32(48): 17431; Lopez-Atalaya et al., Nucleic Acids Res. 41(17):8072-84; Yildirim F et al. Plos ONE 9(4); Benito and Barco. Mol Neurobiol. 289(47):32914-25; Scandaglia et al., Sci Reports 5:17470; Scandaglia et al. Cell Reports 21(1):47-59. Other positions: Lab. Dr. Andrè Fischer. DZNE, Gottingen, Germany. Scientific Coordinator for SourceData at EMBO, Heidelberg, Germany.
- Dragana Jancic studied Medicine and got her MD in the University of Belgrade (Serbia). She became a member of the Marie Curie Excellence Team in November 2004 and worked with us until July 2008. She defended her Ph.D. thesis in December 2008 and obtained the maximal qualification. She is currently a resident in the Psychiatry and Psychotherapy Department at the University Hospitals of Geneva (Switzerland). Thesis: Role of CREB-dependent transcription in the control of hippocampal neurons survival and plasticity. Publications with us: Barco et al. chapter in “Regulation of transcription by neuronal activity: To the nucleus and back” (Springer Sci Pub); Viosca et al. J Neurosci27(47): 12761; Lopez de Armentia et al. J Neurosci27(50): 13909; Viosca et al. Learn Mem 16(3): 193; Jancic et al. Cereb Cortex 19(11): 2535; Sanchis-Segura et al. Front Behav Neurosci3:30; Valor et al. Cell Death Differ 17(19): 1636. Other positions: Resident in Psychiatry and Psychotherapy, University Hospitals of Geneva. Geneva, Switzerland.
Other former lab members:
– Juan Medrano: Graduate student. He carried out his postgraduate studies from January 2017 to July 2020.
– Dr. Rafael Muñoz Viana: Posdoctoral fellow. He was part of the Team from June 2017 to December 2019.
– Marian Llinares: Technician. She was part of the Team from January 2018 to December 2019.
– Emanuele Zaccaria: Graduate student. He was part of the Team from June 2018 to June 2019.
– Alejandro Medrano: Graduate student. He carried out his Master thesis with us in 2015 and his postgraduate studies from January 2016 to July 2018.
– Nuria Cascales Pico: Technician. She was part of the Team from Julio 2016 to November 2017.
– Dr. Jose P. López-Atalaya: Senior postdoctoral fellow and Senior Researcher. He was part of the Team from 2006 to September 2015. He is now Principal Investigator at our Institute leading the «Cellular Plasticity and Neuropathology» group.
– Dr. Romana Tomasoni: Posdoctoral fellow and Visiting Researcher. She joined our lab from 2015 to 2016.
– Dr. Luis M. Valor: Posdoctoral fellow, Senior Researcher and finally co-PI. He was part of the Team from August 2007 to November 2015. He is now Principal Investigator at Hospital Universitario Puerta del Mar in Cadiz, Spain.
– Manuel Alcaraz Iborra: Graduate student. He was part of the Team from June 2012 to January 2014. He then went to the Psychology Department at University of Almeria (Spain) to conduct there his Ph.D. thesis.
– Victor Rovira: After finishing his thesis in the team of Emilio Geijo-Barrientes, he joined the Team from June to December 2013 before moving to , USA for a postdoc in the laboratory of Manuel Castro-Alamancos at Drexel University, Philadelphia, USA.
– Dr. Sven Parkel: Postdoctoral fellow. He was part of the Team from January 2012 to June 2013.
– Dr. Satomi Ito: Postdoctoral fellow. She was part of the Team from April 2009 to March 2013. She later worked at the Institute for Integrated Cell-material Sciences (iCeMS) in Kyoto University and the Okinawa Institute of Science anf Technology (OIST, Ichiro Maruyama’s lab), both in Japan.
– Pierrick Jego:Graduate student. He was part of the Team from October 2010 to September 2011.
– Francisca Almagro: Technician. She was part of the Team from November 2010 to July 2011.
– María Jiménez-Minchan: Technician. She was part of the Team from August 2008 to June 2011.
– Matías M Pulopulos: Graduate student. He was part of the Team from October 2009 to August 2010.
– Dr. Mikel Lopez de Armentia: Senior Researcher. He was part of the Team from November 2004 to August 2009.
– Miguel A. Andrés: Graduate student. He was part of the Team from July 2007 to December 2008.
– Marusa Arencibia: Secretary. She was our administrative officer from 2005 to 2008.
– Valentina Moscato: Graduate student. She worked as a member of the MC Excellence Team form September 2007 to April 2008.
– Petra Gromova: Graduate student. She was in the lab from November 2004 to July 2007.
– Ana Calvo: Graduate student. She was part of the Team from October 2005 to March 2006.
Visitors:
– María Consuelo López Gómez (undergraduate student, Master en Neurociencias UMH). Octubre 2019 – Enero 2021
– Pablo Castellano (undergraduate student, Master en Neurociencias UPO). May-October 2019
– Miguel Fuentes Ramos (undergraduate student, Universidad de Alicante, Alicante). Octubre 2017 – Septiembre 2018
– Marta Alaiz Noya (undergraduate student, Master en Neurociencias UMH). Octubre 2017 – Septiembre 2018
– Paula Mut (undergraduate student, Master en Neurociencias UMH). Octubre 2016 – Septiembre 2017
– Juan Marín (undergraduate student, Master en en Bioinformática y BiologÃa Computacional de la Escuela Nacional de salud- ISCIII). May-October 2019
– Juan Medrano (undergraduate student, Universidad Jaume I, Castellón). July-September 2015
– Agnieszka Czechwska (undergraduate student, Warsaw University, Warsaw, Poland). July-August 2015
– Silvia Colmenero (undergraduate student, Universidad de Alicante, Alicante). may-September 2015
– Alejandro Medrano (undergraduate student, Universidad de Alicante, Alicante). June-October 2014
– Juan Manuel Agulló (undergraduate student, Universidad Autónoma de Barcelona, Barcelona). July-August 2014
– Adriana Magalska (postdoctoral fellow, Dr. Wilczynski’s lab, Nencki Institute, Warsaw, Poland). September to December 2013
– Marilyn Scandaglia (undergraduate student, University of Bologna, Bologna, Italy). April-October 2011
– Jorge Montesinos (undergraduate student, Universidad de Valencia, Valencia). Augus-September 2010
– Raffaela Tulino (undergraduate student, University of Sannio, Sannio, Italy). April-September 2010
– Alessandro Ciccarelli(PhD student, Dr. Giustetto’s lab, University of Torino, Torino, Italy). July 2009 to June 2010
– Paola Tognino (PhD student, Dr. Pizzorusso’s lab, CNR Pisa, Italy). February 2010
– Gianmarco di Mauro (undergraduate student, University of Bologna, Bologna, Italy). May-December 2009
– Vincent Prinz (postdoctoral fellow, Dr. Dirnagl’s lab, Charite Campus Mitte, Berlin, Germany). September 2009
– Jan-Albert Manenschijn (rotation student, Alicante). April 2009
– Eduardo Leiva (rotation PhD student, Alicante). February-March 2009
– Elena Carnero (undergraduate student, Universidad de Granada, Granada). Summer 2008
– Ferah Yildirim (PhD student, Dr. Dirnagl’s lab, Charite Campus Mitte, Berlin, Germany). July 2008
– Oskar Ortiz (PhD student, Dr. Moratalla’s lab, Instituto Cajal, Madrid). April 2008
– Carles Sanchis-Segura (Ramón y Cajal researcher, Universitat Jaume I, Castellon). October-November 2007
– Pankaj Sah (University Professor, University of Queensland, St. Lucia, Australia). September-October 2007
– Cristina Vicente (undergraduate student, Universidad Pablo de Olavide, Sevilla). Summer 2007
– Ignasi Sahun (PhD student, Dr. Dierssens lab,CRG, Barcelona). November 2005