Research Interest

This programme is interested in the physiology of the nervous system and the pathophysiology of different central and peripheral pathological states. In particular, establishing the role of different ion channels implicated in shaping the excitability of sensory neurons of the dorsal root and trigeminal ganglia, and determining which alterations occur during injury, inflammatory, neuropathic or ocular pain and itch. Another research area of the group is glutamatergic signaling. This research is mainly focused on the study of the functional interaction between AMPARs and auxiliary subunits and other interacting proteins, which determine this glutamate receptor function at the synapse. Other lines of research includes functional studies on NMDARs with newly synthesized blocking compounds and positive allosteric modulators in the framework of neurodevelopmental conditions resulting from de novo mutations of NMDAR-encoding genes. Finally, the signaling between microglia and neurons and their involvement in neurodegenerative diseases is also studied.

Technologies & Methods

• Electrophysiology (patch-clamp in cell lines, primary neurons, ex vivo hippocampal slices, field recordings, intracellular recordings)
• Molecular biology
• Biochemistry
• Calcium imaging
• Behavioural neuroscience (i.e. rotarod, open field, novel object recognition, Barnes test, Morris water maze, Sociability, …)
• Animal models of pathology
• Neuropharmacology
• Ex vivo slices
• Primary neuronal cultures
• Primary glial cultures
• Immunofluorescence
• Histology
• Confocal microscopy
• Gene therapy

Active Projects

• • Comprehensive delineation and personalised medicine of GRIN-related disorders, a rare paediatric encephalopathy. Ministerio de Ciencia, Innovación y Universidades. PI19/00348. Xavier Altafaj

• • Fisiología de interactores de receptores AMPA (TARPs y CPT1C) en neuronas y glía. Ministerio de Ciencia, Innovación y Universidades. PID2020-119932GB-I00. David Soto.

• • Medicina personalizada para las GRINpatías, una enfermedad neuropediátrica rara. Fundación Española para la Ciencia y la Tecnologia. 310351. David Soto.

• • Laboratori de Neurofisiologia. Agència de Gestió d’Ajuts Universitaris i de Recerca. 2017SGR737. Xavier Gasull.

• • Molecule-to-man pain network (PAIN-Net). European Union. MSCA-ITN-2016. 721841. Xavier Gasull.

• • Red Temática de Investigación Cooperativa en Salud – Enfermedades oculares. Instituto de Salud Carlos III. Ministerio de Economia y Competitividad. RD16/0008/0014. Xavier Gasull.

• • 2 Confidential agreement

Selected Publications

• • Alonso-Gardón, M., Elorza-Vidal, X., Castellanos, A., La Sala, G., Armand-Ugon, M., Gilbert, A., Di Pietro, C., Pla-Casillanis, A., Ciruela, F., Gasull, X., Nunes, V., Martínez, A., Schulte, U., CohenSalmon, M., Marazziti, D., & Estévez, R. (2021). Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins. Human Molecular Genetics, 30(17), 1649–1665. https://doi.org/10.1093/hmg/ddab155

• • Butler, C. A., Popescu, A. S., Kitchener, E., Allendorf, D. H., Puigdellívol, M., & Brown, G. C. (2021). Microglial phagocytosis of neurons in neurodegeneration, and its regulation. Journal of Neurochemistry, 158(3), 621–639. https://doi.org/10.1111/jnc.15327

• • Comes, N., Gasull, X., & Callejo, G. (2021). Proton Sensing on the Ocular Surface: Implications in Eye Pain. Frontiers in Pharmacology, 12, 773871. https://doi.org/10.3389/fphar.2021.773871

• • García-Recio, A., Santos-Gómez, A., Soto, D., Julia-Palacios, N., García-Cazorla, À., Altafaj, X., & Olivella, M. (2021). GRIN database: A unified and manually curated repertoire of GRIN variants. Human Mutation, 42(1), 8–18. https://doi.org/10.1002/humu.24141

• • Landa, J., Guasp, M., Míguez-Cabello, F., Guimarães, J., Mishima, T., Oda, F., Zipp, F., Krajinovic, V., Fuhr, P., Honnorat, J., Titulaer, M., Simabukuro, M., Planagumà, J., Martínez-Hernández, E., Armangué, T., Saiz, A., Gasull, X., Soto, D., Graus, F., Sabater, L., … GluK2 encephalitis study group (2021). Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2. Annals of Neurology, 90(1), 101–117. https://doi.org/10.1002/ana.26098

• • Latragna, A., Sabaté San José, A., Tsimpos, P., Vermeiren, S., Gualdani, R., Chakrabarti, S., Callejo, G., Desiderio, S., Shomroni, O., Sitte, M., Kricha, S., Luypaert, M., Vanhollebeke, B., Laumet, G., Salinas, G., Smith, E., Ris, L., & Bellefroid, E. J. (2021). Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors. Pain, 10.1097/j.pain.0000000000002536. https://doi.org/10.1097/j.pain.0000000000002536

• • Martínez-Monseny, A. F., Edo, A., Casas-Alba, D., IzquierdoSerra, M., Bolasell, M., Conejo, D., Martorell, L., Muchart, J., Carrera, L., Ortez, C. I., Nascimento, A., Oliva, B., FernándezFernández, J. M., & Serrano, M. (2021). CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings. International Journal of Molecular Sciences, 22(10), 5180. https://doi.org/10.3390/ijms22105180

• • Milde, S., van Tartwijk, F. W., Vilalta, A., Hornik, T. C., Dundee, J. M., Puigdellívol, M., & Brown, G. C. (2021). Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y6 receptor in mice. Journal of Neuroinflammation, 18(1), 225. https://doi.org/10.1186/s12974-021-02280-2

• • Puigdellívol, M., Milde, S., Vilalta, A., Cockram, T., Allendorf, D. H., Lee, J. Y., Dundee, J. M., Pampuščenko, K., Borutaite, V., Nuthall, H. N., Brelstaff, J. H., Spillantini, M. G., & Brown, G. C. (2021). The microglial P2Y6 receptor mediates neuronal loss and memory deficits in neurodegeneration. Cell Reports, 37(13), 110148. https://doi.org/10.1016/j.celrep.2021.110148

• • Rezola, M., Castellanos, A., Gasull, X., & Comes, N. (2021). Functional Interaction Between Caveolin 1 and LRRC8- Mediated Volume-Regulated Anion Channel. Frontiers in Physiology, 12, 691045. https://doi.org/10.3389/fphys.2021.691045

• • Santos-Gómez, A., Miguez-Cabello, F., Juliá-Palacios, N., García-Navas, D., Soto-Insuga, V., García-Peñas, J. J., Fuentes, P., Ibáñez-Micó, S., Cuesta, L., Cancho, R., Andreo-Lillo, P., Gutiérrez-Aguilar, G., Alonso-Luengo, O., Málaga, I., HedreraFernández, A., García-Cazorla, À., Soto, D., Olivella, M., & Altafaj, X. (2021). Paradigmatic De Novo GRIN1 Variants Recapitulate Pathophysiological Mechanisms Underlying GRIN1-Related Disorder Clinical Spectrum. International Journal of Molecular Sciences, 22(23), 12656. https://doi.org/10.3390/ijms222312656

• • Santos-Gómez, A., Miguez-Cabello, F., García-Recio, A., Locubiche-Serra, S., García-Díaz, R., Soto-Insuga, V., GuerreroLópez, R., Juliá-Palacios, N., Ciruela, F., García-Cazorla, À.,Soto, D., Olivella, M., & Altafaj, X. (2021). Disease-associated GRIN protein truncating variants trigger NMDA receptor lossoffunction. Human Molecular Genetics, 29(24), 3859–3871. https://doi.org/10.1093/hmg/ddaa220

• • Vilalta, A., Zhou, Y., Sevalle, J., Griffin, J. K., Satoh, K., Allendorf, D. H., De, S., Puigdellívol, M., Bruzas, A., Burguillos, M. A., Dodd, R. B., Chen, F., Zhang, Y., Flagmeier, P., Needham, L. M., Enomoto, M., Qamar, S., Henderson, J., Walter, J., Fraser, P. E., … Brown, G. C. (2021). Wild-type sTREM2 blocks A aggregation and neurotoxicity, but the Alzheimer’s R47H mutant increases A aggregation. The Journal of Biological Chemistry, 296, 100631. https://doi.org/10.1016/j.jbc.2021.100631

Knowledge transfer & Innovation

• • Combinación nutracéutica y su uso para el tratamiento de trastornos neurológicos. UBTT0421-E. Angeles Garcia, Alfonso Luis De Oyarzabal, Xavier Altafaj