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[ Staff | Summary of Research | Funding Agencies | Publications | Doctoral Theses | Patents | Teaching]





Genetics and Molecular Bases of Multiple Sclerosis



Group Leader
    • Antonio Alcina Madueño     
        email: pulgoso (@ipb.csic.es)
        Tlf: 958181668

    • Fuencisla Matesanz del Barrio     
        email: lindo (@ipb.csic.es)
        Tlf: 958181668



    Staff Research Posdoctoral
    • Tetiana Chernyshova      
    • María Ivanovna Fedetz Ladeyshchykova     


    Technical Assistants
    • Juan Manuel Pérez Pérez     
    • Isabel Beatriz Vidal Cobo     


    Authorized Staff
    • Rafael Cruz Caballero     
    • Jennifer Dámaso Callero     

     

    SUMMARY OF RESEARCH


     

    Genetics and Molecular Bases of Multiple Sclerosis

     

    Multiple sclerosis(MS) is a disease that affects the central nervous system. The prevalence of MS in Spain is 50-100 per 100,000 inhabitants. The symptoms of the disease are varied, mainly affecting the motor skills of the individual. It is caused by the destruction of the myelin sheath of neurons due to an autoimmune attack to the oligodendrocytes, the myelin producing cells. Another feature of the disease is the accelerated death of the neurons, possibly not only as a result of the demyelination process. The etiology of this disease is unknown but it is believed that is triggered by the interaction of genetic and environmental factors .
    To understand the cascade of events leading to the onset of MS, our team is developing several projects to identify molecular pathways affected in MS. For them, we perform Genome wide association study (GWAS) in collaboration with national and international consortia as the Spanish Multiple Sclerosis Network (REEM) or MSBase.


     
     


    In recent years we have focused on the study of the loci IL2RA, CYP27B1, and SP140 CLEC2D. To determine as the variants localized at these loci confer susceptibility to MS, we performed functional studies analyzing the effect of the polymorphisms in the expression and processing of the mRNA. To perform this studies we employ Microarray, RNAseq and real time PCR for quantification of expression in different cell types of healthy and sick individuals and correlate this data with genotypes associated with MS. We also use data from international projects as GTEX projects, 1000 Genomes and ENCODE to determine the functional effect of the variants.


     
     






     


    FUNDING AGENCIES LAST 5 YEARS

    - INTERACCIONES GENE X AMBIENTE EN LA HETEROGENEIDAD DE LA ESCLEROSIS MULTIPLE REVELADA POR POLYGENIC RISK SCORES (PRS). PROYECTO, PN2019 - Proyectos I+D+i «Retos Investigación», Ref: PID2019-110487RB-C21, (2020 - 2024).

    - Biomarcadores de Esclerosis Múltiple: RNA-Seq de células únicas en líquido cefaloraquídeo e integración de datos de GWAS internacional. PROYECTO, J.A.- Retos de la sociedad andaluza, Ref: P18-RT-2623, (2020 - 2023).

    - Red Española de Esclerosis Múltiple (REEM). PROYECTO, PN2016 - REDES TEMATICAS INV. COOPERATIVA, Ref: RD16/0015/0016, (2018 - 2020).

     

     

    PUBLICATIONS LAST 5 YEARS

    -Gil-Varea, E.; Spataro, N.; Villar, L.M.; Tejeda-Velarde, A.; Midaglia, L.; Matesanz, F.; Malhotra, S.; Eixarch, H.; Patsopoulos, N.; Fernández, Ó.; Fernández, Ó.; Oliver-Martos, B.; Saiz, A.; Llufriu, S.; Ramió-Torrentà, L.; Ramió-Torrentà, L.; Quintana, E.; Izquierdo, G.; Alcina, A.; Bosch, E.; Navarro, A.; Montalban, X.; Montalban, X.; Comabella, M.; Comabella, M., Targeted resequencing reveals rare variants enrichment in multiple sclerosis susceptibility genes, Human Mutation, 2020, Vol. 41: 1308-1320, ARTÍCULO, Id:822307

    -Gil-Varea E; Fedetz M; Eixarch H; Spataro N; Villar LM; Urcelay E; Saiz A; Fernández Ó; Leyva L; Ramió-Torrentà L; Vandenbroeck K; Otaegui D; Castillo-Triviño T; Izquierdo G; Malhotra S; Bosch E; Navarro A; Alcina A; Montalban X; Matesanz F; Comabella M., A New Risk Variant for Multiple Sclerosis at 11q23.3 Locus Is Associated with Expansion of CXCR5+ Circulating Regulatory T Cells, Journal of Clinical Medicine, 2020, Vol. 9: 6253-625, ARTÍCULO, Id:819279

    -Gómez-Fernández P; Lopez de Lapuente Portilla A; Astobiza I; Mena J; Urtasun A; Altmann V; Matesanz F; Otaegui D; Urcelay E; Antigüedad A; Malhotra S; Montalban X; Castillo-Triviño T; Espino-Paisán L; Aktas O; Buttmann M; Chan A; Fontaine B; Gourraud PA; Hecker M; Hoffjan S; Kubisch C; Kümpfel T; Luessi F; Zettl UK; Zipp F; Alloza I; Comabella M; Lill CM; Vandenbroeck K., The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis., Cells, 2020, Vol. 9: 1751-175, ARTÍCULO, Id:819277

    -Dominguez-Mozo, M.I.; Perez-Perez, S.; Villar, L.M.; Oliver-Martos, B.; Villarrubia, N.; Matesanz, F.; Costa-Frossard, L.; Pinto-Medel, M.J.; García-Sánchez, M.I.; Ortega-Madueño, I.; Lopez-Lozano, L.; Garcia-Martinez, A.; Izquierdo, G.; Fernández, Ó.; Álvarez-Cermeño, J.C.; Arroyo, R.; Alvarez-Lafuente, R., Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab, Scientific Reports, 2020, Vol. 10: 1-14244, ARTÍCULO, Id:815823

    -Malhotra, S.; Costa, C.; Eixarch, H.; Keller, C.W.; Amman, L.; Martínez-Banaclocha, H.; Midaglia, L.; Sarró, E.; Machín-Díaz, I.; Villar, L.M.; Triviño, J.C.; Oliver-Martos, B.; Parladé, L.N.; Calvo-Barreiro, L.; Matesanz, F.; Vandenbroeck, K.; Urcelay, E.; Martínez-Ginés, M.L.; Tejeda-Velarde, A.; Fissolo, N.; Castilló, J.; Sanchez, A.; Robertson, A.A.B.; Clemente, D.; Prinz, M.; Pelegrin, P.; Lünemann, J.D.; Espejo, C.; Montalban, X.; Comabella, M., NLRP3 inflammasome as prognostic factor and therapeutic target in primary progressive multiple sclerosis patients, Brain, a journal of neurology, 2020, Vol. 143: 1414-1430, ARTÍCULO, Id:807041

    -Vilariño-Güell, C.; Zimprich, A.; Martinelli-Boneschi, F.; Herculano, B.; Wang, Z.; Matesanz, F.; Urcelay, E.; Vandenbroeck, K.; Leyva, L.; Gris, D.; Massaad, C.; Quandt, J.A.; Traboulsee, A.L.; Encarnacion, M.; Bernales, C.Q.; Follett, J.; Yee, I.M.; Criscuoli, M.G.; Deutschländer, A.; Reinthaler, E.M.; Zrzavy, T.; Mascia, E.; Zauli, A.; Esposito, F.; Alcina, A.; Izquierdo, G.; Espino-Paisán, L.; Mena, J.; Antigüedad, A.; Urbaneja-Romero, P.; Ortega-Pinazo, J.; Song, W.; Sadovnick, A.D., Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease, PLoS Genetics, 2019, Vol. 15: , ARTÍCULO, Id:766650

    -Pérez-Núñez, I.; Karaky, M.; Fedetz, M.; Barrionuevo, C.; Izquierdo, G.; Matesanz, F.; Alcina, A., Splice-site variant in ACSL5: a marker promoting opposing effect on cell viability and protein expression, European Journal of Human Genetics, 2019, Vol. : , ARTÍCULO, Id:763391

    -Karaky, M.; Fedetz, M.; Potenciano, V.; Andrés-León, E.; Codina, A.E.; Barrionuevo, C.; Alcina, A.; Matesanz, F., SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-κB inhibition, Human Molecular Genetics, 2018, Vol. 27: 4012-4023, ARTÍCULO, Id:735380

    -Gil-Varea, E.; Urcelay, E.; Vilariño-Güell, C.; Costa, C.; Midaglia, L.; Matesanz, F.; Rodríguez-Antigüedad, A.; Oksenberg, J.; Espino-Paisan, L.; Dessa Sadovnick, A.; Saiz, A.; Villar, L.M.; García-Merino, J.A.; Ramió-Torrentà, L.; Triviño, J.C.; Quintana, E.; Robles, R.; Sánchez-López, A.; Arroyo, R.; Alvarez-Cermeño, J.C.; Vidal-Jordana, A.; Malhotra, S.; Fissolo, N.; Montalban, X.; Comabella, M., Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course 06 Biological Sciences 0604 Genetics 11 Medical and Health Sciences 1109 Neurosciences, Journal of Neuroinflammation, 2018, Vol. 15: 1-265, ARTÍCULO, Id:734143


     

     

    DOCTORAL THESES LAST 5 YEARS

     

     

     


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