Lines of investigation
The goal of our lab is to understand how brain’s innate immune cells integrate within neural circuits to influence brain function in health and disease. The questions we pursue are grounded in understanding the interplay between brain physiology and the brain’s innate immune system, as a central axis controlling homeostasis and disease. Our research is focused in two lines: (1) Understanding integrated brain circuits: we aim to elucidate the roles of neuron-microglia interactions at multiple levels, from synapses to neural circuits, in the control of brain function in health and disease. (2) Investigating cellular plasticity of immune cells of the brain: the ability of innate immune cells of the brain to adopt alternative fates when exposed to different conditions is now emerging as an important process in normal physiology and in disease conditions, such as aging and neurodegenerative diseases. We seek to understand how microglia cells interpret cues from their tissue microenvironment to adopt specialized roles. We have particular interest in unveiling the molecular mechanisms regulating the transitions and maintenance of distinct phenotypic and functional states of brain’s innate immune cells.
Our ultimate goal is to develop novel approaches for the treatment of chronic neurodegenerative conditions by modulating immunity and neuroinflammation. We combine animal models of neurodegenerative disease (epilepsy) and neuroinflammation, samples from patients with the associated pathologies, mouse genetics, transcriptomics and epigenetic analyses at cell population and single-cell levels, and state-of-the-art histological, cellular and molecular biology methods and techniques.
- Cell-specific vulnerability to metabolic failure: the crucial role of parvalbumin expressing neurons in creatine transporter deficiency. Elsa Ghirardini , Giulia Sagona, Angel Marquez-Galera , Francesco Calugi, Carmen M Navarron , Francesco Cacciante , Siwei Chen , Federica Di Vetta , Lorenzo Dadà , Raffaele Mazziotti , Leonardo Lupori , Elena Putignano , Pierre Baldi , Jose P Lopez-Atalaya , Tommaso Pizzorusso, Laura Baroncelli. Acta Neuropathol Commun. 2023 11(1): 34 https://doi.org/10.1186/s40478-023-01533-w
- Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution Chinnappa K, Cárdenas A, Prieto-Colomina A, Villalba A, Márquez-Galera Á, Soler R, Nomura Y, Llorens E, Tomasello U, López-Atalaya JP, Borrell V Sci Adv 2022 8(2):eabj4010 https://doi.org/10.1126/sciadv.abj4010
- 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
- Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming Herrero-Navarro Á, Puche-Aroca L, Moreno-Juan V, Sempere-Ferràndez A, Espinosa A, Susín R, Torres-Masjoan L, Leyva-Díaz E, Karow M, Figueres-Oñate M, López-Mascaraque L, López-Atalaya JP, Berninger B, López-Bendito G Sci Adv 2021 7(15):eabe8978 https://doi.org/10.1126/sciadv.abe8978
- SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation Rueda-Carrasco J, Martin-Bermejo MJ, Pereyra G, Mateo MI, Borroto A, Brosseron F, Kummer MP, Schwartz S, López-Atalaya JP, Alarcon B, Esteve P, Heneka MT, Bovolenta P EMBO Rep 2021 22(11):e51696 https://doi.org/10.15252/embr.202051696
- 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
- Repression of Irs2 by let-7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium Fernández V, Martínez-Martínez MÁ, Prieto-Colomina A, Cárdenas A, Soler R, Dori M, Tomasello U, Nomura Y, López-Atalaya JP, Calegari F, Borrell V EMBO J 2020 39(21):e105479 https://doi.org/10.15252/embj.2020105479
- 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