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Investigación
Patología Mitocondrial y ELA
Líneas de investigación
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Endotelio Funcional
Nuestro objetivo principal es estudiar la funcionalidad del sistema endotelial como herramienta diagnóstica y terapéutica en diferentes patologías humanas principalmente del sistema respiratorio.
Líneas de investigación. (1) Contribución del sistema vascular a enfermedades pulmonares mediadas por trastornos inflamatorios o focos de fibrosis. (2) Evaluación y regulación de la transición endotelio-mesénquima e implicación patológica. (3) Efecto de la contaminación ambiental sobre la fisiología pulmonar. (4) Reprogramación endotelial hacia iPS. (5) Papel de las células endoteliales en regeneración tisular.
Proyectos de investigación
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Proyectos como Investigador Principal.
- “Mecanismos endoteliales implicados en la protección, reparación y regeneración tisular tras alteraciones inflamatorias o fibrosis en enfermedades respiratorias raras”. 2019-2023. FIS, PI18CIII/00040 (IERPY-M 389/18).
- “Contribución del endotelio vascular a la patología inflamatoria y fibrótica en las enfermedades pulmonares raras”. 2016-2018. FIS, PI15CIII/00044 (IERPY 1149/16).
- “Regulation of the polarization of tumor associated macrophages by the ARF gene and its functionality on tumor angiogenesis”. 2013-2016. Instituto Salud Carlos III. TPY-M 1068/13.
Proyectos como Investigador Colaborador.
- “Estudio de la contribución de la microbiota, el metabolismo y la inmunidad innata a la aparición y progresión de las enfermedades pulmonares intersticiales”. 2023-2024. AESI IERPY-M 308/20 (PI20CIII/00018).
- “Impulso de investigación del sistema inmune en la resistencia de las terapias antitumorales”. 2014-2017. Merck, S.L.U. Proyecto de colaboración entre Merck y IIER-ISCIII. TVP 1316/13.
- “Caracterización genética y funcional de la histiocitosis pulmonar de células de Langerhans: implicaciones diagnósticas y terapéuticas”. 2013-2016. SEPAR EPID-Futuro (04-2013).
- “Caracterización genética y funcional de la histiocitosis pulmonar de células de Langerhans: implicaciones diagnósticas y terapéuticas”. 2013-2015. Fundación Mutua Madrileña.
Publicaciones destacadas
Aβ42 Peptide Promotes Proliferation and Gliogenesis in Human Neural Stem Cells
Aβ42 Peptide Promotes Proliferation and Gliogenesis in Human Neural Stem Cells. Bernabeu-Zornoza A, Coronel R, Palmer C, Calero M, Martínez-Serrano A, Cano E, Zambrano A, Liste I. Mol Neurobiol. 2019 Jun;56(6):4023-4036. doi: 10.1007/s12035-018-1355-7. Epub 2018 Sep 27. PMID: 30259399.
PUBMED DOIIntersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor through regulation of Sprouty2-Cbl interaction
Okur MN, Zhu JO, Fong CW, Martinez N, Garcia-Dominguez C, Rojas JM, Guy G & O'Bryan J. Intersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor through regulation of Sprouty2-Cbl interaction. Molecular and Cellular Biology. 2012; 32(4):817-25. doi:10.1128/MCB.05647-11
DOIImmune profiling of gliomas reveals a connection with Tau function and the tumor vasculature
Cejalvo T*, Gargini R*, Segura-Collar B, Mata P, Herránz B, Cantero D, Ruano Y, García-Pérez D, Pérez-Núñez A, Ramos A, Hernández-Laín A, Cruz Martín-Soberón M, Sánchez-Gómez P# and Sepúlveda-Sánchez JM# (# Co-corresponding author) (* Co-1st author). (2020) Immune profiling of gliomas reveals a connection with Tau function and the tumor vasculature. Cancers. 12-11, pp.E3230. PMID: 33147752doi: 10.3390/cancers12113230
DOIThe complex regulation of NIS expression and activity in thyroid and extrathyroidal tissues
Riesco-Eizaguirre G*, Santisteban P and De la Vieja A*. The complex regulation of NIS expression and activity in thyroid and extrathyroidal tissues. Endocrine-Related Cancer 2021 28(10):T141-T165. PMID: 34387194. doi: 10.1530/ERC-21-0217
DOINew insights into the genetic etiology of Alzheimer's disease and related dementias
Bellenguez et al. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022 54(4):412-436. doi: 10.1038/s41588-022-01024-z.
DOIThe transcription factor LEF1 interacts with NFIX and switches isoforms during adult hippocampal neural stem cell quiescence
Garcia-Corzo L, Calatayud-Baselga I, Casares-Crespo L, Mora-Martinez C, Julian Escribano-Saiz J, Hortiguela R, et al. The transcription factor LEF1 interacts with NFIX and switches isoforms during adult hippocampal neural stem cell quiescence. Front Cell Dev Biol. 2022;10:912319. Q1
Neurogenesis is increased in human neural stem cells by Aβ40 peptide
Bernabeu-Zornoza, A.; Coronel, R.; Palmer, C.; Martín, A.; López-Alonso, V.; Liste, I. (2022). Neurogenesis is increased in human neural stem cells by Aβ40 peptide. Int J Mol Sci. 23, 5820. doi: 10.3390/ijms23105820.
DOISynthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors
Castaño T, Wang H, Campillo NE, Ballester S, González-García C, Hernández J, Pérez C, Cuenca J, Pérez-Castillo A, Martínez A, Huertas O, Gelpí JL, Luque FJ, Ke H and Gil C. Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors. ChemMedChem. (2009) 4-5, pp.866-876.PMCID: PMC2952885 doi:10.1002/cmdc.200900043
PUBMED DOIEpigenetic silencing of OR and TAS2R genes expression in human orbitofrontal cortex at early stages of sporadic Alzheimer's disease
Alves VC, Figueiro-Silva J, Ferrer I, Carro E. Epigenetic silencing of OR and TAS2R genes expression in human orbitofrontal cortex at early stages of sporadic Alzheimer's disease. Cell Mol Life Sci. 2023 Jul 5;80(8):196. doi: 10.1007/s00018-023-04845-1.
DOIΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival. The Journal of Pathology.
Pastor-Morate D, Amigo-Morán L, Garranzo-Asensio M, Rejas-González R, Carnicero P, Rodríguez N, Pérez-Robledo JP, Barderas R, Prieto-Nieto I, Domínguez G. ΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival. The Journal of Pathology. 2024;263:328.
DOIEstablishment and characterization of a rainbow trout heart endothelial cell line with susceptibility to viral hemorrhagic septicemia virus (VHSV) Fish Shellfish
A Luque; A González-Granja; L González; C Tafalla. 2014. Establishment and characterization of a rainbow trout heart endothelial cell line with susceptibility to viral hemorrhagic septicemia virus (VHSV) Fish Shellfish Immunol. 2014 May;38(1):255-64. https://doi.org/10.1016/j.fsi.2014.03.027.
DOIRole of Amyloid Precursor Protein (APP) and Its Derivatives in the Biology and Cell Fate Specification of Neural Stem Cells
Coronel R, Bernabeu-Zornoza A, Palmer C, Muñiz-Moreno M, Zambrano A, Cano E, Liste I. Mol Neurobiol. 2018 Sep;55(9):7107-7117. doi: 10.1007/s12035-018-0914-2. Epub 2018 Jan 30. PMID: 29383688
PUBMED DOIRegulation of CBP andTip60 coordinates histone acetylation at local and global level during Ras-induced transformation
Sánchez-Molina S, Estarás C, Oliva JL, Akizu N, Asensio-Juan E, Rojas JM & Martínez-Balbás MA. Regulation of CBP andTip60 coordinates histone acetylation at local and global level during Ras-induced transformation. Carcinogenesis 2014; 35(10):2194-202. doi:10.1093/carcin/bgu111
DOICellular plasticity and tumor microenvironment in gliomas: the struggle to hit a moving target
Gargini R, Segura-Co llar B, Sánchez-Gómez P. (2020) Cellular plasticity and tumor microenvironment in gliomas: the struggle to hit a moving target. Cancers. 12(6): E1622. PMID: 32570988 doi: 10.3390/cancers12061622
DOIToxicity of nanoplastics for zebrafish embryos, what we know and where to go next
Torres-Ruiz M*, De la Vieja A, Gonzalez MD, Lopez ME, Castaño-Calvo A, Cañas-Portilla AI. Toxicity of nanoplastics for zebrafish embryos, what we know and where to go next. Science of the Total Environment 2021 797:149125. PMID: 34346375. doi: 10.1016/j.scitotenv.2021.149125
DOIColocalization Analysis of Peripheral Myelin Protein-22 and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice
Di Tomaso MV, Vázquez Alberdi L, Olsson D, Cancela S, Fernández A, Rosillo JC, Reyes Ábalos AL, Álvarez Zabaleta M, Calero M, Kun A. Colocalization Analysis of Peripheral Myelin Protein-22 and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice. Biomolecules. 2022 12(3):456. doi: 10.3390/biom12030456.
DOIPrevalence and Population Diversity of Listeria monocytogenes Isolated from Dairy Cattle Farms in the Cantabria Region of Spain
Varsaki A, Ortiz S, Santorum P, López P, López-Alonso V, Hernández M, Abad D, Rodríguez-Grande J, Ocampo-Sosa AA, Martínez-Suárez JV. Prevalence and Population Diversity of Listeria monocytogenes Isolated from Dairy Cattle Farms in the Cantabria Region of Spain. Animals (Basel). 2022 Sep 19;12(18):2477. Q1
Oligomeric and fibrillar species of Aβ42 diversely affect human neural stem cells
Bernabeu-Zornoza, A.; Coronel, R.; Palmer, C.; López-Alonso, V.; Liste, I. (2021). Oligomeric and fibrillar species of Aβ42 diversely affect human neural stem cells. Int J Mol Sci. 22, 9537. doi: 10.3390/ijms22179537.
DOIBeta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells
Martín-Saavedra FM, González-García C, Bravo B and Ballester S. Beta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells. Molecular Immunology (2008)45-15, pp.4008-4019. ISSN 0161-5890 doi:10.1016/j.molimm.2008.06.006
PUBMED DOISalivary Lactoferrin Expression in a Mouse Model of Alzheimer's Disease
Antequera D, Moneo D, Carrero L, Bartolome F, Ferrer I, Proctor G, Carro E. Salivary Lactoferrin Expression in a Mouse Model of Alzheimer's Disease. Front Immunol. 2021 Sep 30;12:749468. doi: 10.3389/fimmu.2021.749468.
DOIFunctional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis
Montero-Calle A, Jiménez de Ocaña S, Benavente-Naranjo R, Rejas-González R, Bartolomé RA, Martínez-Useros J, Sanz R, Dziaková J, Fernández-Aceñero MJ, Mendiola M, et al. Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis. Cells. 2023; 12:2548.
DOIBeta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism
Zovein AC, Luque A, Turlo KA, Hofmann JJ, Yee KM, Becker MS, Fassler R, Mellman I, Lane TF, Iruela-Arispe ML. Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell. 2010 Jan 19;18(1):39-51. Los dos mpriemros autores han contribuido igualmente en este trabajo. doi: 10.1016/j.devcel.2009.12.006.
DOIEffects of lung and airway epithelial maturation cocktail on the structure of lung bud organoids
Effects of lung and airway epithelial maturation cocktail on the structure of lung bud organoids. Magro-Lopez E, Palmer C, Manso J, Liste I, Zambrano A. Stem Cell Res Ther. 2018 Jul 11;9(1):186. doi: 10.1186/s13287-018-0943-9. PMID: 29996941; PMCID: PMC6042463.
PUBMED DOIShoc2/Sur8 protein regulates neurite outgrowth
León G, Sánchez-Ruiloba L, Perez-Rodriguez A, Gragera T, Martinez N, Hernandez S, Anta B, Calero O, Garcia-Domínguez CA, Dura LM, Peña-J Jimenez D, Castro J, Zarich N, Sanchez-Gomez P, Calero M, Iglesias T, Oliva JL & Rojas JM. Shoc2/Sur8 protein regulates neurite outgrowth. PloS ONE. 2014; 9(12):e114837. doi:10.1371/journal.pone.0114837
DOIThe IDH-Tau-EGFR triad defines the neovascular landscape of diffuse gliomas by controlling mesenchymal differentiation
Gargini R*, Segura-Collar B*, Hernández-SanMiguel E, Garcia-Escudero V, Romero-Bravo A, Herránz B, Núñez FJ, Cantero D, García-Pérez D, Ayuso-Sacido A, Seoane J, Sepúlveda-Sánchez JM, Hernández-Laín A, Castro MG, García-Escudero R, Ávila J* and Sánchez-Gómez P*. (* Co-corresponding author) (* Co-1st author) (2020) The IDH-Tau-EGFR triad defines the neovascular landscape of diffuse gliomas by controlling mesenchymal differentiation. Sci. Transl. Med.12 (527). PMID: 31969485 doi: 10.1126/scitranslmed.aax1501
DOIRadio-Iodide Treatment: From Molecular Aspects to the Clinical View
De la Vieja A* and Riesco-Eizaguirre G. Radio-Iodide Treatment: From Molecular Aspects to the Clinical View. Cancers 2021 13(5):995. PMID: 33673669. doi: 10.3390/cancers13050995
DOIBlood DNAMethylation Patterns in Older Adults With Evolving Dementia
Pérez RF, Alba-Linares JJ, Tejedor JR, Fernández AF, Calero M, Román-Domínguez A, Borrás C, Viña J, Ávila J, Medina M, Fraga MF. Blood DNAMethylation Patterns in Older Adults With Evolving Dementia. J Gerontol A Biol Sci Med Sci. 2022 77(9):1743-1749. doi: 10.1093/gerona/glac068.
DOINeurogenesis Is Increased in Human Neural Stem Cells by A40 Peptide
Bernabeu-Zornoza A, Coronel R, Palmer C, Lopez-Alonso V, Liste I. Neurogenesis Is Increased in Human Neural Stem Cells by A40 Peptide. Int. J. Mol. Sci. 2022, 23, 5820. Q1
Aβ42 peptide promotes proliferation and gliogenesis in human neural stem cells
Bernabeu-Zornoza, A.; Coronel, R.; Palmer, C.; Calero, M.; Martínez-Serrano, A.; Cano, E.; Zambrano, A.; Liste, I. (2019). Aβ42 peptide promotes proliferation and gliogenesis in human neural stem cells. Mol Neurobiol. 56, 4023-4036. doi: 10.1007/s12035-018-1355-7.
DOIBeta-interferon unbalances the peripheral T cell proinflammatory response in experimental autoimmune encephalomyelitis
Martín-Saavedra FM, Flores N, Dorado B, Eguiluz C, Bravo B, García-Merino A and Ballester S. Beta-interferon unbalances the peripheral T cell proinflammatory response in experimental autoimmune encephalomyelitis. Molecular immunology (2007) 44-14, pp.3597-3607. ISSN 0161-5890 doi:10.1016/j.molimm.2007.03.002
PUBMED DOIAmyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models
de la Cueva M, Antequera D, Ordoñez-Gutierrez L, Wandosell F, Camins A, Carro E, Bartolome F. Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer's disease experimental models. Sci Rep. 2022 Jun 16;12(1):10092. doi: 10.1038/s41598-022-13683-3.
DOIMetabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer
Montero-Calle A, Gomez de Cedron M, Quijada-Freire A, Solís-Fernandez G, López-Alonso V, Espinosa-Salinas I, Pelaez-García A, Fernandez-Aceñero MJ, Ramírez de Molina A, Barderas R. Metabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer. Front. Oncol. 2022; 12
DOISPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150
Barbáchano A, Fernández-Barral A, Pereira F, Segura MF, Ordóñez-Morán P, Carrillo-de Santa Pau E, González-Sancho JM, Hanniford D, Martínez N, Costales-Carrera A, Real FX, Pálmer HG, Rojas JM, Hernando E & Muñoz A. SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150. Oncogene. 2016; 35(23):2991-3003. doi:10.1038/onc.2015.366
DOIThe EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas
Segura-Collar B, Gargini R, Tovar-Ambel E, Hernández-SanMiguel E, Epifano C, Pérez de Castro I, Hernández-Laín A, Casas-Tintó S, Sánchez-Gómez P. (2020) The EGFR-TMEM167A-p53 Axis Defines the Aggressiveness of Gliomas. Cancers 12(1):208. PMID: 31947645 doi: 10.3390/cancers12010208
DOIRadio-Iodide Treatment: From Molecular Aspects to the Clinical View
Gutiérrez-Salmerón M, García-Martínez JM, Martinez-Useros J, Fernandez-Aceñedo MJ, Viollet B, Olivier S, Chauha J, Lucena SR, De la Vieja A, Goding CR and Chocarro-Calvo A* and García-Jiménez C*. Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer. Plos Biology 2020 6: e3000732. PMID 32603375. DOI: 10.1371/journal.pbio.3000732
PUBMED DOIDiagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases
Schmitz M, Villar-Piqué A, Hermann P, Escaramís G, Calero M, Chen C, Kruse N, Cramm M, Golanska E, Sikorska B, Liberski PP, Pocchiari M, Lange P, Stehmann C, Sarros S, Martí E, Baldeiras I, Santana I, Žáková D, Mitrová E, Dong XP, Collins S, Poleggi A, Ladogana A, Mollenhauer B, Kovacs GG, Geschwind MD, Sánchez-Valle R, Zerr I, Llorens F. Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases. Brain. 2022 145(2):700-712. doi: 10.1093/brain/awab350.
DOIAnchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells
TT Chen; A Luque; S Lee; SM Anderson; T Segura; ML Iruela-Arispe. 2010. Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells. J Cell Biol. 2010 Feb 22;188(4):595-609. https://doi.org/10.1083/jcb.200906044.
DOIStructural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis
Al-Chalabi, Al Khleifat A, Iacoangeli A, van Vugt J, Moisse M, Zwamborn R, van der Spek R, Shatunov A, Cooper-Knock, Topp S, Byrne R, Gellera C, López Alonso V et al. “Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis". NPJ Genomic Medicine 2022, 7(1). Q1.
Neuronal and glial differentiation of human neural stem cells is regulated by amyloid precursor protein (APP) levels
Coronel, R.; Lachgar, M.; Bernabeu-Zornoza, A.; Palmer, C.; Domínguez-Alvaro, M.; Revilla, A.; Ocaña, I.; Fernández, A.; Martínez-Serrano, A.; Cano, E.; Liste, I. (2019). Neuronal and glial differentiation of human neural stem cells is regulated by amyloid precursor protein (APP) levels. Mol Neurobiol. 56, 1248-1261. doi: 10.1007/s12035-018-1167-9.
DOIInformación adicional
La Unidad de Patología Mitocondrial (PMIT), perteneciente a la Unidad Funcional de Investigación en enfermedades Crónicas (UFIEC) del Instituto de Salud Carlos III (ISCIII), tiene como misión la realización de actividades de investigación básica y translacional en el campo de la disfunción mitocondrial y el metabolismo energético en las enfermedades mitocondriales y en la Esclerosis Lateral Amiotrófica (ELA), constituyéndose así en un recurso de soporte científico-técnico para la investigación, diagnóstico y tratamiento de estas enfermedades raras.
Actualmente desarrolla un proyecto financiado por la Fundación HNA, para el análisis de los genomas de pacientes con ELA, como parte de su colaboración con el Consorcio Internacional MinE, cuyo fin es el estudio del genoma de miles de pacientes, entre ellos cerca de 500 de origen español de los que se dispone de muestras en el laboratorio. En este proyecto se pretenden detectar nuevos genes candidatos responsables de la enfermedad, genes de susceptibilidad y asociaciones génicas. Además, a partir de nuevas mutaciones posiblemente patogénicas detectadas, estudia su patofisiología en la línea celular de motoneurona NSC-34.