Lines of investigation
Our laboratory investigates the molecular underpinnings of age-related cognitive decline and neurodegeneration, with a particular interest in Alzheimer’s disease (AD). We hypothesize that genetics, epigenetics, and the interaction of both – “neuro-epi-genetics” –, have long-lasting effects on brain function.
To tackle this hypothesis, we use mouse models and human samples, and combine molecular and behavioral neuroscience with state-of-the-art single-cell, next generation sequencing (NGS), bioinformatic tools and epi-genetic editing.
Our ultimate goal is to better understand age-related brain malfunctioning and to identify new biomarkers and targets to further develop current dementia-related therapies.
Representative Publications
- Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons. Del Blanco B, Niñerola S, Martín-González AM, Paraíso-Luna J, Kim M, Muñoz-Viana R, Racovac C, Sánchez-Mut JV, Ruan Y and Barco A. Nature Communications. 2024 15, 1781 (2024) https://www.nature.com/articles/s41467-024-45773-3
- A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment. Pérez, R.F., Tezanos, P., Peñarroya, A., González-Ramón, A., Urdinguio, R.G., Gancedo-Verdejo, J., Tejedor, J.R., Santamarina-Ojeda, P., Alba-Linares, J.J., Sainz-Ledo, L., Roberti, A., López, V., Mangas, C., Moro, M., Cintado, E., Muela, P., Rodríguez-Santamaría, M., Ortea, I., Iglesias-Rey, R., Castilla-Silgado, J., Tomás-Zapico, C., Iglesias-Gutiérrez, E., Sanchez-Mut, J.V., Trejo, J.L., Fernández, A.F. and Fraga, M.F. Nature Communications. 2024 15, art. 5829 https://www.nature.com/articles/s41467-024-49608-z#citeas
- PM20D1 is a quantitative trait locus associated with Alzheimer’s disease Sanchez-Mut JV,Heyn H, Silva BA, Dixsaut L, Garcia-Esparcia P, Vidal E, Sayols S, Glauser L, Monteagudo-Sánchez A, Perez-Tur J, Ferrer I, Monk D, Schneider B, Esteller M, Gräff Nat Med 2018 24(5):598 https://doi.org/10.1038/s41591-018-0013-y
- Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns Sanchez-Mut JV,Heyn H, Vidal E, Moran S, Sayols S, Delgado-Morales R, Schultz MD, Ansoleaga B Garcia-Esparcia P, Pons-Espinal M, Martinez de Lagran M, Dopazo J, Rabano A, Avila J, Dierssen M, Ira Lott, Ferrer I, Ecker JR, Esteller M Transl Psychiatry 2016 6(1):e718 https://doi.org/10.1038/tp.2015.214
- Epigenetic Alterations in Alzheimer’s Disease. Sanchez-Mut JV , Gräff J. Front Behav Neurosci 2015 0,6159722222 https://doi.org/10.3389/fnbeh.2015.00347
- Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer’s disease Jose Vicente Sanchez-Mut , Ester Aso, Holger Heyn, Tadashi Matsuda, Christoph Bock, Isidre Ferrer, Manel Esteller Hippocampus 2014 24(4):363 https://doi.org/ 10.1002/hipo.22245
- DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease Jose V Sanchez-Mut , Ester Aso, Nicolas Panayotis, Ira Lott, Mara Dierssen, Alberto Rabano, Rocio G Urdinguio, Agustin F Fernandez, Aurora Astudillo, Jose I Martin-Subero, Balazs Balint, Mario F Fraga, Antonio Gomez, Cecile Gurnot, Jean-Christophe Roux, Jesus Avila, Takao K Hensch, Isidre Ferrer, Manel Esteller Brain 2013 136(Pt 10):3018 https://doi.org/10.1093/brain/awt237