Research Interest

This programme focuses on understanding of the mechanisms of neurodegenerative diseases from different angles to integrate this knowledge in designing effective pharmacological and molecular therapies. Research interests include investigating neurodegenerative diseases from the mouse behaviour (motor, cognitive and psychiatric) to the cellular and molecular level. In addition of finding new therapeutic targets we are also interested in identifying biomarkers of the disease progression. To this end, we collaborate with clinicians to obtain blood, fibroblasts and cerebrospinal fluid from patients.

Technologies & Methods

• Behavioural tests to assess cognitive, motor dysfunction and depression-like phenotype.
• Western Blot, Immunofluorescence, immunoprecipitation, proteomics/phosphoproteomics, intracerebral viral injections, extracellular vesicles isolation techniques, primary neuronal and glial cultures from mice and rats
• RT-qPCR, non-radioactive northern blot
• Transcriptomics, bioinformatic and biostatistical pipelines for RNA seq analysis, in vitro functional screening
• Analysis of dendritic spine density and morphology (Golgi staining and gene-gun dyolistic labelling)
• Confocal microscopy
• SUnSET method to analyze protein synthesis
• Fluorescence-activated nuclear suspension imaging (FANSI)

Active Projects

• • Ayuda para la Incorporación Estable de Doctores 2019. Ministerio de Ciencia, Innovación y Universidades. IED2019- 001065-I. Cristina Malagelada

• • Astrocytes at the hub of neuronal dysfunction in Huntington´s disease: Dissecting the role of ARMS/kidins 220 on astrocyte secretome. European Huntington´s disease Foundation. 1130_201217. Silvia Gines.

• • Contracte del Programa Juan de la Cierva-Formació 2019. Ministerio de Economia y Competitividad. FJCI2019-39633-I. Eulalia Marti.

• • Conveni de col·laboració en relació al finançament d’una recerca conjunta. University Hospital Ulm. Silvia Gines.

• • Descifrando el papel de la metilación m6A del ARN como un nuevo nivel de regulación de la expresión génica en la patología de la enfermedad de Huntington. Ministerio de Ciencia e Innovación. PID2020-116474RB-I00. Veronica Ines Brito.

• • CIBER de Epidemiología y Salud Pública. Ministerio de Sanidad y Consumo. CB06/02/0058. Eulalia Marti.

• • Estudio de la función transneuronal de la proteína RTP801/ REDD1 en la neuroinflamación en la enfermedad de Alzheimer. Ministerio de Ciencia e Innovación. PID2020-119236RB-I00. Cristina Malagelada.

• • Exploring M6A modifications as critical modulators of mutant htt alternative splicing. Hereditary Disease Foundation. Veronica Ines Brito.

• • Fragmentos de los tRNAs como mediadores de los procesos neurodegenerativos: implicaciones en la enfermedad de Huntington. Ministerio de Ciencia e Innovación. PID2020-113953RB-I00. Eulalia Marti.

• • Gliotransmissors i receptors de cannabinoides en l’origen dels dèficits cognitius i de plasticitat sinàptica en la malaltia de Huntington. Fundació La Marató de TV3. 30/C/2020. Silvia Gines.

• • La enfermedad de Huntington como una laminopatía: interacción entre cerebro y la periferia. Ministerio de Ciencia, Innovación y Universidades. PID2019-106447RB-I00. Esther Perez.

• • Phospho-proteome analysis of PBMCs in LRRK2 mutation carriers: expansion & validation of findings of the Barcelona LRRK2 Biorepository. Michael J. Fox Foundation for Parkinson’s research. MJFF-000858. Cristina Malagelada.

• • Transmitofagia entre astrocitos y neuronas: una nueva forma de comunicación entre neurona y glía en la enfermedad de Huntington?. Ministerio de Ciencia, Innovación y Universidades. RTI2018-094374-B-I00. Silvia Gines.

• • 1 Confidential agreement.

Selected Publications

• • Alcalá-Vida, R., Garcia-Forn, M., Castany-Pladevall, C., Creus- Muncunill, J., Ito, Y., Blanco, E., Golbano, A., Crespí-Vázquez, K., Parry, A., Slater, G., Samarajiwa, S., Peiró, S., Di Croce, L., Narita, M., & Pérez-Navarro, E. (2021). Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington’s disease. EMBO Molecular Medicine, 13(2), e12105. https://doi.org/10.15252/emmm.202012105

• • Costas-Insua, C., Moreno, E., Maroto, I. B., Ruiz-Calvo, A., Bajo-Grañeras, R., Mart\’\in-Gutiérrez, D., Diez-Alarcia, R., Vilaró, M. T., Cortés, R., Garc\’\ia-Font, N., Mart\’\in, R., Espina, M., Botta, J., Ginés, S., McCormick, P. J., Sánchez-Prieto, J., Galve-Roperh, I., Mengod, G., Urigüen, L., … Guzmán, M. (2021). Identification of BiP as a CB1 Receptor-Interacting Protein That Fine-Tunes Cannabinoid Signaling in the Mouse Brain. Journal of Neuroscience, 41(38), 7924–7941. https://doi.org/10.1523/JNEUROSCI.0821-21.2021

• • Creus-Muncunill, J., Guisado-Corcoll, A., Venturi, V., Pantano, L., Escaramís, G., García de Herreros, M., Solaguren-Beascoa, M., Gámez-Valero, A., Navarrete, C., Masana, M., Llorens, F., Diaz-Lucena, D., Pérez-Navarro, E., & Martí, E. (2021). Huntington’s disease brain-derived small RNAs recapitulate associated neuropathology in mice. Acta Neuropathologica, 141(4), 565– 584. https://doi.org/10.1007/s00401-021-02272-9

• • Fan, Y., Nirujogi, R. S., Garrido, A., Ruiz-Martínez, J., Bergareche-Yarza, A., Mondragón-Rezola, E., Vinagre-Aragón, A., Croitoru, I., Gorostidi Pagola, A., Paternain Markinez, L., Alcalay, R., Hickman, R. A., Düring, J., Gomes, S., Pratuseviciute, N., Padmanabhan, S., Valldeoriola, F., Pérez Sisqués, L., Malagelada, C., Ximelis, T., … Sammler, E. M. (2021). R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in human peripheral blood neutrophils. Acta Neuropathologica, 142(3), 475–494. https://doi.org/10.1007/s00401-021-02325-z

• • Fissolo, N., Matute-Blanch, C., Osman, M., Costa, C., Pinteac, R., Miró, B., Sanchez, A., Brito, V., Dujmovic, I., Voortman, M., Khalil, M., Borràs, E., Sabidó, E., Issazadeh-Navikas, S., Montalban, X., & Comabella Lopez, M. (2021). CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS. Neurology Neuroimmunology & Neuroinflammation, 8(2), e941. https://doi.org/10.1212/NXI.0000000000000941

• • Meneses-Salas, E., Garcia-Forn, M., Castany-Pladevall, C., Lu, A., Fajardo, A., Jose, J., Wahba, M., Bosch, M., Pol, A., Tebar, F., Klein, A. D., Zanlungo, S., Pérez-Navarro, E., Grewal, T., Enrich, C., & Rentero, C. (2021). Lack of Annexin A6 Exacerbates Liver Dysfunction and Reduces Lifespan of Niemann-Pick Type C Protein-Deficient Mice. American Journal of Pathology, 191(3), 475–486. https://doi.org/10.1016/j.ajpath.2020.12.009

• • Nurm, K., Sepp, M., Castany-Pladevall, C., Creus-Muncunill, J., Tuvikene, J., Sirp, A., Vihma, H., Blake, D. J., Perez-Navarro, E., & Timmusk, T. (2021). Isoform Specific Reduction of the Basic Helix-Loop-Helix Transcription Factor TCF4 Levels in Huntington’s Disease. eNeuro, 8(5), eNEURO.0197-21.2021. https://doi.org/10.1523/ENEURO.0197-21.2021

• • Pérez-Sisqués, L., Martín-Flores, N., Masana, M., Solana- Balaguer, J., Llobet, A., Romaní-Aumedes, J., Canal, M., Campoy-Campos, G., García-García, E., Sánchez-Fernández, N., Fernández-García, S., Gilbert, J. P., Rodríguez, M. J., Man, H. Y., Feinstein, E., Williamson, D. L., Soto, D., Gasull, X., Alberch, J., & Malagelada, C. (2021). RTP801 regulates motor cortex synaptic transmission and learning. Experimental Neurology, 342, 113755. https://doi.org/10.1016/j.expneurol.2021.113755

• • Pérez-Sisqués, L., Sancho-Balsells, A., Solana-Balaguer, J., Campoy-Campos, G., Vives-Isern, M., Soler-Palazón, F., Anglada-Huguet, M., López-Toledano, M. Á., Mandelkow, E. M., Alberch, J., Giralt, A., & Malagelada, C. (2021). RTP801/ REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease. Cell Death & Disease, 12(6), 616. https://doi.org/10.1038/s41419-021-03899-y

• • Pérez-Sisqués, L., Solana-Balaguer, J., Campoy-Campos, G., Martín-Flores, N., Sancho-Balsells, A., Vives-Isern, M., Soler-Palazón, F., Garcia-Forn, M., Masana, M., Alberch, J., Pérez-Navarro, E., Giralt, A., & Malagelada, C. (2021). RTP801/REDD1 is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease. Biomolecules, 12(1), 34. https://doi.org/10.3390/biom12010034

• • Torres, A. G., & Martí, E. (2021). Toward an Understanding of Extracellular tRNA Biology. Frontiers in Molecular Biosciences, 8, 662620. https://doi.org/10.3389/fmolb.2021.662620

Knowledge transfer & Innovation

• • Method for predicting the onset of extrapyramidal symptoms (EPS) induced by an antipsicotic-based treatment. AVCRI196. Sergi Mas, Patricia Gasso, Cristina Malagelada, Miquel Bernardo, Amalia Lafuente

• • Methods and pharmaceutical composition for the treatment of neurodegerative disease. UBTT0329-E. Jean-Antoine Girault, Albert Giralt, Veronica Brito, Silvia Gines