Functional genomics of neurodegenerative diseases. PI: Eulàlia Martí Puig

Presentation

Different classes of RNA molecules that do not encode for proteins (non-coding RNAs or ncRNAs) modulate gene expression through diverse mechanisms and constitute a crucial layer of biological regulation. ncRNAs are specially enriched in the nervous system, where their highly specific and dynamic expression is essential in developmental processes and the correct function of the adult brain. The ncRNA repertoire is fundamental for neuron-specific functions and its perturbation is mechanistically related with neuropathological processes.

The main research interest in our group is to identify ncRNA mechanisms contributing to the onset and progression of age-related neurodegenerative disorders. We aim at understanding disease-driven deregulation of ncRNAs and their role in neuronal dysfunction. Our final purpose is to discover ncRNA-gene expression networks underlying neuro-pathogenic processes with the aim to understand disease mechanisms and identifying pathways for therapeutic intervention.

KEYWORDS: Non-coding RNA, regulation of gene expression, pathogenic mechanisms, neuronal dysfunction, biomarkers, therapeutic targets


Eulàlia Martí Puig
Investigador Principal
eulalia.marti@ub.edu

 


Ana Gamez Valéro
Investigadora Postdoctoral
a.gamez@ub.edu

 


Georgia Escaramís Babiano

Investigadora Postdoctoral
gescaramis@ub.edu

 


Anna Guisado Corcoll

Estudiant de doctorat
annaguisado@ub.edu

 


Marina Herrero Lorenzo

Estudiant de doctorat
marina.130595@gmail.com

 


Maria Solaguren Beascoa

Estudiant de doctorat
mariasolagurenbeascoa@gmail.com

Identification of non-coding RNAs pathways involved in neurodegenerative diseases pathogenesis.

Therapeutic designs based on the modulation of the activity of non coding RNAs.

RNAs as biomarkers of disease progression.

  • Human Biology Project Fellowship to Ana Gamez-Valero

2021 HDSA
(2021-2023)

  • tRNA fragments as mediators of neurodegenerative processess: implications in Huntington’s disease (tRFs4HD)

PID2020-113953RB-I00 (2021-2023)
Ministerio de Ciencia e Innovación

  • Juan de la Cierva postdoctoral contract to Ana Gámez Valero

(2021-2022)

  • Análisis de ARNs con repeticiones CAG como factores patogénicos en la enfermedad de Huntington: implicaciones translacionales en enfermedades de poliglutamina

SAF2017-88452-R (2018-2020)
Ministerio de Economia y Competitividad

  • Epidemiología y Salud Pública

CB06/02/0058 (2018-2019)
Programa Consolider, accions CIBER, Ministerio de Sanidad y Consumo

  • Identification of small non coding RNAs (sncRNAs) contributing to early neuronal dysfunction in Parkinson's disease (iRPaD)

SAF2014-60551-R
Ministerio de Economía y Competitividad

  • Variants genètiques en malalties comuns; perfils de RNAs no codificants en trastorns neurodegeneratius; moduladors ambientals dels factors genètics en malaltia humana

CIBERESP

For more information for PI publications click in the link:
ORCID: https://orcid.org/0000-0002-1030-3158
ResearcherID: http://www.researcherid.com/rid/L-2775-2014

 

Solana-Balaguer J, Campoy-Campos G, Martín-Flores N, Pérez-Sisqués L, Sitjà-Roqueta L, Kucukerden M, Gámez-Valero A, Coll-Manzano A, Martí E, Pérez-Navarro E, Alberch J, Soriano J, Masana M, Malagelada C. Neuron-derived extracellular vesicles contain synaptic proteins, promote spine formation, activate trkb-mediated signaling, and preserve neuronal complexity. J Extracell Vesicles 2023 Sep;12(9): e12355. doi: 10.1002/ jev2.12355. PMID: 37743539

Solaguren-Beascoa, M., Gámez-Valero, A., Escaramís, G., Hererro-Lorenzo, M., Ortiz, A.M., Minguet, C., Gonzalo, R., Bravo, I., Costa, M., Martí, E. Phospho-RNA-Seq highlights specific small RNA profiles in plasma extracellular vesicles. Int. J. Molec. Science 2023 Jul 19;24(14): 11653. doi: 10.3390/ ijms241411653. PMID: 37511412

Herrero-Lorenzo, M., Pérez-Perez, J., Escaramís, G., Pérez-González, R., Kulisewsky, J., Gámez-Valero, A., Martí, E. D10 Plasma extracellular small RNAS are early deregulated in Huntington’s disease and correlate with cognitive symptoms. Journal of Neurology, Neurosurgery, and Psychiatry (2022) 93(Suppl 1): A23.2-A24. Doi: 10.1136/jnnp-2022-ehdn.66

Pupak, A., Sancho-Balsells, A., Alcalá-Vida, R., Espina, M., Giralt, A., Martí, E., Ørom U. A. V., Ginés, S., Brito, V. Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington's disease mice. Cell Mol Life Sci 2022 Jul 11;79(8):416. doi: 10.1007/s00018-022-04444-6. PMID: 35819730

Schmitz, M., Villar-Piqué, A., Hermann, P., Escaramís, G., Calero, M., Chen,C., Kruse, N., Cramm, M., Golanska, E., Sikorska, B., Liberski, P. P., Pocchiari, M., Lange,P.,  Stehmann, C., Sarros, S., Martí, E., Baldeiras, I., Santana, I., Zákova, D., Mitrová, E., Dong, X.P., Collins, S., Poleggi, A., Ladogana, A.,  Mollenhauer, B., Kovacs, G.G., Geschwind, M. D., Sánchez-Valle, R., Zerr, I., Llorens, F., Diagnostic accuracy and prognostic utility of CSF biomarkers in genetic prion diseases. Brain 2022 Apr 18; 145(2):700-712. doi: 10.1093/ brain/awab350. PMID: 35288744

Ruiz-Arenas, C., Hernandez-Ferrer, C., Vives-Usano, M., Marí, S., Quintela, I., Mason, D., Cadiou, S., Casas, M., Andrusaityte, S., Gutzkow, K.B., Vafeiadi, M., Wright, J., Lepeule, J., Grazuleviciene, R., Chatzi, L., Carracedo, Á., Estivill, X., Marti, E., Escaramís G, Vrijheid M, González JR, Bustamante M. Identification of autosomal cis expression quantitative trait methylation (cis eQTMs) in children's blood. Elife 2022 Mar 18;11:e65310. doi: 10.7554/ eLife.65310. PMID: 35302492

Matamoros-Angles, A., Hervera, A., Soriano, J., Marti, E., Carulla, P., Llorens, F., Nuvolone, M., Aguzzi, A., Ferrer, I., Gruart, A., Delgado-García, J. M., del Rio, J. A. Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability. BMC Biology 2022 Jan 13;20(1): 17. doi: 10.1186/ s12915-021-01203-0. PMID: 35027047

Torres, A. G. & Martí, E. Toward an Understanding of Extracellular tRNA Biology. 2021 Apr 15;8: 662620. doi: 10.3389/ fmolb.2021.662620. eCollection 2021. PMID: 33937338

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. Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice. Acta Neuropathol. 2021 Feb 6. doi: 10.1007/ s00401-021- 02272-9. PMID: 33547932

Gamez-Valero A, Guisado-Corcoll A, Herrero-Lorenzo M, Solaguren-Beascoa M, Martí E. Non-coding RNAs as sensors of Oxidative Stress in Neurodegeneerative Diseases, Antioxidants (Basel) 2020 Nov 8;9 (11): 1095. doi: 10.3390/ antiox9111095. PMID: 33171576

Vives-Usano M, (26 authors), Martí E, Vrijheid M, Bustamante M. In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children  BMC Med. 2020 Aug 19;18(1): 243. doi: 10.1186/ s12916-020- 01686-8. PMID: 32811491

Pallarès-Albanell J, Zomeño-Abellán MT, Escaramís G, Pantano L, Soriano A, Segura MF, Martí E. A High-Throughput Screening Identifies MicroRNA Inhibitors That Influence Neuronal Maintenance and/or Response to Oxidative Stress. Molecular Therapy Nucleic Acids, Sep 6;17:374-387. doi: 10.1016/ j.omtn.2019.06.007. Epub 2019 Jun 20. PMID: 31302497

Diaz Lucena D; Escaramís G, Villar-Piqué A, Hermann P, Schmitz M, Varges D, Santana I, del Rio JA, Martí E, Ferrer i, Baldeiras i, Zerr i. A new tetra-plex fluorimetric assay for the quantification of cerebrospinal fluid β-amyloid42, total-tau, phospho-tau and α-synuclein in the differential diagnosis of neurodegenerative dementia. J of Neurology, Sep;267(9): 2567-2581. doi: 10.1007/ s00415-020- 09870-9. Epub 2020 May 5. PMID: 32372181

Pantano L, Pantano F, Marti E, Ho Sui S. Visualization of the small RNA transcriptome using seqclusterViz. F1000Res. 2019 Feb 28;8. pii: ISCB Comm J-232. doi: 10.12688 /f1000research. 18142.1. eCollection 2019. PMID: 30984380

Llorens F, Thüne K, Martí E, Kanata E, Dafou D, Díaz-Lucena D, Vivancos A, Shomroni O, Zafar S, Schmitz M, Michel U, Fernández-Borges N, Andréoletti O, Del Río JA, Díez J, Fischer A, Bonn S, Sklaviadis T, Torres JM, Ferrer I, Zerr I. Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis. PLoS Pathog. 2018 Jan 22;14(1): e1006802. doi: 10.1371/ journal.ppat.1006802. eCollection 2018 Jan. PMID: 29357384

Pagès A, Dotu I, Pallarès-Albanell J, Martí E, Guigó R, Eyras E. The discovery potential of RNA processing profiles. Nucleic Acids Res. 2018 Feb 16;46 (3):e15. doi: 10.1093 /nar/gkx1115. PMID: 29155959

Llorens F, Thüne K, Andrés-Benito P, Tahir W, Ansoleaga B, Hernández-Ortega K, Martí E, Zerr I, Ferrer I. MicroRNA Expression in the Locus Coeruleus, Entorhinal Cortex, and Hippocampus at Early and Middle Stages of Braak Neurofibrillary Tangle Pathology. J Mol Neurosci. 2017 Oct;63(2):206-215. doi: 10.1007/s12031-017-0971-4. Epub 2017 Sep 5. PMID: 28871468

Rué L, Bañez-Coronel M, Creus-Muncunill J, Giralt A, Alcalá-Vida R, Mentxaka G, Kagerbauer B, Zomeño-Abellán MT, Aranda Z, Venturi V, Pérez-Navarro E, Estivill X, Martí E. Targeting CAG repeat RNAs reduces Huntington's disease phenotype independently of huntingtin levels. J Clin Invest. 2016 Nov 1;126 (11): 4319-4330. doi: 10.1172/ JCI83185. Epub 2016 Oct 10. PMID: 27721240

Martí E. RNA toxicity induced by expanded CAG repeats in Huntington's disease. Brain Pathol. 2016 Nov;26 (6): 779-786. doi: 10.1111/ bpa.12427. Review. PMID: 27529325

Pantano L, Friedländer MR, Escaramís G, Lizano E, Pallarès-Albanell J, Ferrer I, Estivill X, Martí E. Specific small-RNA signatures in the amygdala at premotor and motor stages of Parkinson's disease revealed by deep sequencing analysis. Bioinformatics. 2016 Mar 1;32 (5): 673-81. doi: 10.1093/ bioinformatics/ btv632. Epub 2015 Nov 2. PMID: 26530722

Friedländer MR, Lizano E, Houben AJ, Bezdan D, Báñez-Coronel M, Kudla G, Mateu-Huertas E, Kagerbauer B, González J, Chen KC, LeProust EM, Martí E, Estivill X. Evidence for the biogenesis of more than 1,000 novel human microRNAs.Genome Biol. 2014 Apr 7;15(4): R57. doi: 10.1186/ gb-2014-15-4-r57. PMID: 24708865

Mateu-Huertas E, Rodriguez-Revenga L, Alvarez-Mora MI, Madrigal I, Willemsen R, Milá M, Martí E*, Estivill X* (co-corresponding). Blood expression profiles of fragile X premutation carriers identify candidate genes involved in neurodegenerative and infertility phenotypes. Neurobiol Dis. 2014 May; 65:43-54. doi: 10.1016 /j.nbd.2013.12.020. Epub 2014 Jan 10. PMID: 24418349

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