Lines of investigation
Our research focuses on the molecular bases of neuronal plasticity, learning and memory, and other long-lasting modifications of the animal’s behavior. More precisely, we are investigating the role of specific transcription and epigenetic factors in these processes. We also aim to determine how the malfunction of epigenetic mechanisms leads to different pathological situations in the nervous system. To tackle these questions, we use a multidisciplinary approach that combines mouse genetics, genomics, behavioral and electrophysiological analyses and molecular and cellular biology techniques. From the methodological point of view, we are particularly interested in the application of genomic profiling techniques based on next generation sequencing (NGS) and epigenetic editing approaches in the nervous system.
We currently work on two main lines of research:
• Interplay of transcriptional and epigenetic mechanisms in activity-dependent transcription: Alterations in the patterns of neuronal gene expression are thought to underlie the long-lasting changes in the strength of synaptic connections responsible for the encoding of memories in the nervous system. We are investigating the participation of specific activity-regulated transcription factors, such as CREB and SRF, and epigenetic enzymes, such as CBP and p300, in this process. We are also interested in determining the role of the covalent modification of chromatin in neuroplasticity.
• Contribution of epigenetic mechanisms to intellectual disability (ID) disorders: We investigate the contribution of epigenetic mechanisms, such as histone acetylation and methylation, to the pathoetiology of different neurological conditions associated with cognitive impairments and autism, including Rubinstein-Taybi syndrome and X-linked intellectual disability. Towards this end, we generate and characterize mouse models for these conditions, explore the molecular causes of the disease and tackle new therapies.
Representative Publications
- 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
- Targeting epigenetic dysregulation in autism spectrum disorders. Macarena L. Herrera, Juan Paraíso-Luna , Isabel Bustos-Martínez, Ángel Barco. Trends in Molecular Medicine. 2024 30(11): p1028-1046 https://doi.org/10.1016/j.molmed.2024.06.004
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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