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Investigación
Endotelio Funcional
Líneas de investigación
Contenidos con Investigacion .
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
Contenidos con Investigacion .
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
ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leukocyte trans-endothelial migration
S Hortelano; R López-Fontal; PG Través; N Villa; C Grashoff; L Boscá; A Luque. 2010. ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leukocyte trans-endothelial migration. Cardiovasc Res. 2010. May 1;86(2):283-92. https://doi.org/10.1093/cvr/cvq050.
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.
Phage-Derived and Aberrant HaloTag Peptides Immobilized on Magnetic Microbeads for Amperometric Biosensing of Serum Autoantibodies and Alzheimer's Disease Diagnosis
Alejandro Valverde, Ana Montero-Calle, Beatriz Arévalo, Dr. Pablo San Segundo-Acosta, Dr. Verónica Serafín, Miren Alonso-Navarro, Guillermo Solís-Fernández, Prof. José M. Pingarrón, Dr. Susana Campuzano, Dr. Rodrigo Barderas. Phage-Derived and Aberrant HaloTag Peptides Immobilized on Magnetic Microbeads for Amperometric Biosensing of Serum Autoantibodies and Alzheimer's Disease Diagnosis. Analysis and Sensing. 2021; 1:161.
DOIPGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes
Anta B, Pérez-Rodríguez A, Castro J, García-Domínguez CA, Ibiza S, Martínez N, Durá LM, Hernández S, Gragera T, Peña-Jiménez D, Yunta M, Zarich N, Crespo P, Serrador JM, Santos E, Muñoz A, Oliva JL & Rojas-Cabañeros JM. PGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes. Cell Death and Disease. 2016; 7(7):e2311. doi:10.1038/cddis.2016.219
DOIA Two-Dimensional Human Minilung System (Model) for Respiratory Syncytial Virus Infections
A Two-Dimensional Human Minilung System (Model) for Respiratory Syncytial Virus Infections. Magro-Lopez E, Guijarro T, Martinez I, Martin-Vicente M, Liste I, Zambrano A. Viruses. 2017 Dec 10;9(12):379. doi: 10.3390/v9120379. PMID: 29232863; PMCID: PMC5744153.
PUBMED DOILa Nutrición de yodo en España. Necesidades para el Futuro
Vila L, Lucas A, Donnay S, De la Vieja A, Wengrovicz S, Santiago P, Bandrés O, Velasco I, García-Fuentes E, Ares S, Moreno JC, Espada M, Muñoz JA, Galofré JC and Puig-Domingo M. La Nutrición de yodo en España. Necesidades para el Futuro. Endocrinología Diabetes y Nutrición 2019 67(1):61-69. PMID: 30962160. DOI: 10.1016/j.endinu.2019.02.009
DOIDifferentially Aquaporin 5 Expression in Submandibular Glands and Cerebral Cortex in Alzheimer's Disease
Antequera D, Carrero L, Cunha Alves V, Ferrer I, Hernández-Gallego J, Municio C, Carro E. Differentially Aquaporin 5 Expression in Submandibular Glands and Cerebral Cortex in Alzheimer's Disease. Biomedicines. 2022 Jul 8;10(7):1645. doi: 10.3390/biomedicines10071645.
DOIThe activity of interleukin-4 receptor alpha-chain promoter is regulated by a GT box element
13. Dorado B, Martín-Saavedra FM, Jerez MJ, Ballester S. The activity of interleukin-4 receptor alpha-chain promoter is regulated by a GT box element. Molecular Immunology (2006) 43-11, pp.1808-1816. ISSN 0161-5890 doi:10.1016/j.molimm.2005.10.016
PUBMED DOINovel Functions of the Neurodegenerative-Related Gene Tau in Cancer
Gargini R*, Segura-Collar B*, Sánchez-Gómez P. (* Co-1st author) (2019) Novel Functions of the Neurodegenerative-Related Gene Tau in Cancer. Front Aging Neurosci. 11:231. PMID: 31551755 doi: 10.3389/fnagi.2019.00231
DOIEffects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells
Sandoval, L., Rosca, A., Oniga, A., Zambrano, A., Ramos, J.J., González, M.C., Liste, I., Motas, M. (2019). Effects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells. Sci Total Environ. 683, 445-454. doi: 10.1016/j.scitotenv.2019.05.270.
DOIUnraveling autoimmune and neurodegenerative diseases by amperometric serological detection of antibodies against aquaporin-4
Arévalo B, Blázquez M, Serafín V, Montero-Calle A, Calero M, Valverde A, Barderas R, Campuzano S, Yáñez-Sedeño P, Pingarrón JM. Unraveling autoimmune and neurodegenerative diseases by amperometric serological detection of antibodies against aquaporin-4. Bioelectrochemistry. 2022 144:108041. doi: 10.1016/j.bioelechem.2021.108041.
DOIOligomeric and Fibrillar Species of Abeta42 Diversely Affect Human Neural Stem Cells
Bernabeu-Zornoza A, Coronel R, Palmer C, Lopez-Alonso V, Liste I. Oligomeric and Fibrillar Species of Abeta42 Diversely Affect Human Neural Stem Cells. Int J Mol Sci. 2021,22(17). Q1
The Molecular Misreading of APP and UBB Induces a Humoral Immune Response in Alzheimer’s Disease Patients with Diagnostic Ability
Montero-Calle, A., San Segundo-Acosta, P., Garranzo-Asensio, M., Rábana, A, Barderas, R. The Molecular Misreading of APP and UBB Induces a Humoral Immune Response in Alzheimer’s Disease Patients with Diagnostic Ability. Mol Neurobiol 57, 1009–1020 (2020)
DOIThe CSN3 subunit of the COP9 signalosome interacts with the HD region of Sos1 regulating stability of this GEF protein.
Zarich N, Anta B, Fernández-Medarde A, Ballester A, de Lucas MP, Cámara AB, Anta B, Oliva JL, Rojas-Cabañeros JM & Santos E. The CSN3 subunit of the COP9 signalosome interacts with the HD region of Sos1 regulating stability of this GEF protein. Oncogenesis. 2019; 8(1):2. doi:10.1038/s41389-018-0111-1
DOIInduction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus
Induction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus. Martínez I, García-Carpizo V, Guijarro T, García-Gomez A, Navarro D, Aranda A, Zambrano A. Virulence. 2016 May 18;7(4):427-42. doi: 10.1080/21505594.2016.1144001. Epub 2016 Jan 25. PMID: 26809688; PMCID: PMC4871660.
PUBMED DOIIncreased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer's Disease
Blanco-Palmero VA, Rubio-Fernández M, Antequera D, Villarejo-Galende A, Molina JA, Ferrer I, Bartolome F, Carro E. Increased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer's Disease. Biomedicines. 2021 Aug 27;9(9):1094. doi: 10.3390/biomedicines9091094.
DOIGrb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1
Zarich N, Oliva JL, Martínez N, Jorge R, Ballester A, Gutiérrez-Eisman S, García-Vargas S, Rojas JM. Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1. Molecular Biology of the Cell (2006) 17-8, pp.3591-3597.PMCID: PMC1525251 doi:10.1091/mbc.E05-12-1104
PUBMED DOIOncogenic dependence of glioma cells to Kish/TMEM167A regulation of vesicular trafficking
Portela M#, Segura B#, Argudo I, Sáiz A, Gargini R, Sánchez-Gómez P*, Casas-Tintó S*. (* Co-corresponding authors) (# Co-1st author) (2019) Oncogenic dependence of glioma cells to Kish/TMEM167A regulation of vesicular trafficking. GLIA 67(2):404-417. PMID: 30506943 doi: 10.1002/glia.23551
DOIBrain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: Achievements and weaknesses
Coronel, R.; García-Moreno, E.; Siendones, E.; Barrero, M.J.; Martinez-Delgado, B.; Santos-Ocaña, C.; Liste, I.; Cascajo- Almenara, M.V. (2024). Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: Achievements and weaknesses. Front Cell Neurosci. 18. doi: 10.3389/fncel.2024.1403734.
DOISurvival Patterns of Human Prion Diseases in Spain, 1998-2018: Clinical Phenotypes and Etiological Clues
Tejedor-Romero L, López-Cuadrado T, Almazán-Isla J, Calero M, García López FJ, de Pedro-Cuesta J. Survival Patterns of Human Prion Diseases in Spain, 1998-2018: Clinical Phenotypes and Etiological Clues. Front Neurosci. 2022 15:773727. doi: 10.3389/fnins.2021.773727. eCollection 2021.
DOIATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
Tazelaar GHP, Boeynaems S, De Decker M, van Vugt J, Kool L, Goedee HS, et al. ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization. Brain Commun. 2020,2(2):fcaa064. Q1
Magnetic microbeads-based amperometric immunoplatform for the rapid and sensitive detection of N6-methyladenosine to assist in metastatic cancer cells discrimination
Eloy Povedano, María Gamella, Rebeca M. Torrente-Rodríguez, Ana Montero-Calle, María Pedrero, Guillermo Solís-Fernández, Fernando Navarro-Villoslada, Rodrigo Barderas, Susana Campuzano, José M. Pingarrón. Magnetic microbeads-based amperometric immunoplatform for the rapid and sensitive detection of N6-methyladenosine to assist in metastatic cancer cells discrimination. Biosensors and Bioelectronics. 2021; 171:112708
DOISOS GEFs in health and disease
Baltanás FC, Zarich N, Rojas- Cabañeros JM & Santos E. SOS GEFs in health and disease. BBA-Reviews on Cancer. 2020; 188445. doi: 10.1016/j.bbcan.2020.188445
DOIThyroid hormone increases bulk histones expression by enhancing translational efficiency
Thyroid hormone increases bulk histones expression by enhancing translational efficiency. Zambrano A, García-Carpizo V, Villamuera R, Aranda A. Mol Endocrinol. 2015 Jan;29(1):68-75. doi: 10.1210/me.2014-1235. PMID: 25422881; PMCID: PMC5414774.
PUBMED DOIEpidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer
Gutiérrez-Salmerón M, Chocarro-Calvo A, García-Martínez JM, de la Vieja A, García-Jiménez C. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer. Endocrinol Diabetes Nutr. 2017 Feb; 64(2):109-117. (https://www.ncbi.nlm.nih.gov/pubmed/28440775) doi:10.1016/j.endinu.2016.10.005
PUBMED DOISalivary lactoferrin as biomarker for Alzheimer's disease: Brain-immunity interactions
Bermejo-Pareja F, Del Ser T, Valentí M, de la Fuente M, Bartolome F, Carro E. Salivary lactoferrin as biomarker for Alzheimer's disease: Brain-immunity interactions. Alzheimers Dement. 2020 Aug;16(8):1196-1204. doi: 10.1002/alz.12107.
DOIOcoxin Modulates Cancer Stem Cells and M2 Macrophage Polarization in Glioblastoma
Hernández SanMiguel, E.; Gargini, R.; Cejalvo, T., Segura-Collar B, Núñez-Hervada P, Hortigüela R, Sepúlveda-Sánchez JM, Hernández-Laín A, Pérez-Núñez A, Sanz E, Sánchez Gómez, P. (2019) Ocoxin Modulates Cancer Stem Cells and M2 Macrophage Polarization in Glioblastoma. Oxid.Med.Cell. Longev. pp.9719730. PMID: 31467641. doi: 10.1155/2019/9719730
DOIImpact of environmental neurotoxic: current methods and usefulness of human stem cells
Rosca, A.; Coronel, R.; Moreno, M.; González, R.; Oniga, A.; Martín, A.; López, V.; González, M.C.; Liste, I. (2020). Impact of environmental neurotoxic: current methods and usefulness of human stem cells. Heliyon. 6, e05773. doi: 10.1016/j.heliyon.2020.e05773.
DOIGenomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study
de Rojas I, Hernández I, Montrreal L, Quintela I, Calero M, Royo JL, Huerto Vilas R, González-Pérez A, Franco-Macías E, Macías J, Menéndez-González M, Frank-García A, Diez-Fairen M, Lage C, García-Madrona S, Aguilera N, García-González P, Puerta R, Sotolongo-Grau O, Alonso-Lana S, Rábano A, Arias Pastor A, Pastor AB, Corma-Gómez A, Martín Montes A, Martínez Rodríguez C, Buiza-Rueda D, Periñán MT, Rodriguez-Rodriguez E, Alvarez I, Rosas Allende I, Pineda JA, Bernal Sánchez-Arjona M, Fernández-Fuertes M, Mendoza S, Del Ser T, Gr Ace/Degesco Consortium, Garcia-Ribas G, Sánchez-Juan P, Pastor P, Bullido MJ, Álvarez V, Real LM, Mir P, Piñol-Ripoll G, García-Alberca JM, Medina M, Orellana A, Butler CR, Marquié M, Sáez ME, Carracedo Á, Tárraga L, Boada M, Ruiz A. Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study. J Pers Med. 2021 11(12):1318. doi: 10.3390/jpm11121318.
DOIImpact of environmental neurotoxic: current methods and usefulness of human stem cells
Rosca A, Coronel R, Moreno M, Gonzalez R, Oniga A, Martin A, et al. Impact of environmental neurotoxic: current methods and usefulness of human stem cells. Heliyon. 2020,6(12):e05773. Q1
Bringing to Light the Importance of the miRNA Methylome in Colorectal Cancer Prognosis Through Electrochemical Bioplatforms
Povedano E, Ruiz-Valdepeñas Montiel V, Sebuyoya R, Torrente-Rodríguez RM, Garranzo-Asensio M, Montero-Calle A, Pingarrón JM, Barderas R, Bartosik M, Campuzano S. Bringing to Light the Importance of the miRNA Methylome in Colorectal Cancer Prognosis Through Electrochemical Bioplatforms. Analytical Chemistry 2024;96:4580
DOIMinilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract
Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza O, Yuste J & Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiology Spectrum. 2022; 10(3):e00453-22. doi: 10.1128/spectrum.00453-22
DOIThe thyroid hormone receptor β induces DNA damage and premature senescence
The thyroid hormone receptor β induces DNA damage and premature senescence. Zambrano A, García-Carpizo V, Gallardo ME, Villamuera R, Gómez-Ferrería MA, Pascual A, Buisine N, Sachs LM, Garesse R, Aranda A. J Cell Biol. 2014 Jan 6;204(1):129-46. doi: 10.1083/jcb.201305084. PMID: 24395638; PMCID: PMC3882795.
PUBMED DOIFrom obesity to diabetes and cancer: epidemiological links and role of therapies
García-Jiménez C, Gutiérrez-Salmerón M, Chocarro-Calvo A, García-Martínez JM, Castaño A, De la Vieja A. From obesity to diabetes and cancer: epidemiological links and role of therapies. Br J Cancer. 2016 Mar 29; 114(7):716-22. (https://www.ncbi.nlm.nih.gov/pubmed/26908326) doi: 10.1038/bjc.2016.37
PUBMED DOIAquaporin 5 in Alzheimer's disease: a link between oral and brain pathology?
Municio C, Carro E. Aquaporin 5 in Alzheimer's disease: a link between oral and brain pathology? Neural Regen Res. 2023 Jul;18(7):1491-1492. doi: 10.4103/1673-5374.361545.
DOIThe Netrin-4/ Neogenin-1 axis promotes neuroblastoma cell survival and migration
Villanueva AA, Falcón P, Espinoza N, R LS, Milla LA, Hernández-SanMiguel E, Torres VA, Sanchez-Gomez P, Palma V. (2017) The Netrin-4/ Neogenin-1 axis promotes neuroblastoma cell survival and migration. Oncotarget 8(6):9767-9782. PMID: 28038459 doi: 18632/oncotarget.14213
DOIAnalysis of Benzalkonium Chloride Resistance and Potential Virulence of Listeria monocytogenes Isolates Obtained from Different Stages of a Poultry Production Chain in Spain
Lopez-Alonso V, Ortiz S, Corujo A, Martinez-Suarez JV. Analysis of Benzalkonium Chloride Resistance and Potential Virulence of Listeria monocytogenes Isolates Obtained from Different Stages of a Poultry Production Chain in Spain. J Food Prot. 2020,83(3):443-51. Q2
Physiological and pathological effects of amyloid-β species in neural stem cell biology
Bernabeu-Zornoza, A.; Coronel, R.; Palmer, C.; Monteagudo, M.; Zambrano, A.; Liste, I. (2019). Physiological and pathological effects of amyloid-β species in neural stem cell biology. Neural Regen Res. 14, 2035-2042. doi: 10.4103/1673-5374.262571.
DOISelenium Increases Thyroid-Stimulating Hormone-Induced Sodium/Iodide Symporter Expression Through Thioredoxin/Apurinic/Apyrimidinic Endonuclease 1-Dependent Regulation of Paired Box 8 Binding Activity. Antioxid Redox Signal. 2016 May 20; 24(15):855-66. (*co-corresponding authors) (IF: 6,337)
Leoni SG, Sastre-Perona A, De la Vieja A, Santisteban P. Selenium Increases Thyroid-Stimulating Hormone-Induced Sodium/Iodide Symporter Expression Through Thioredoxin/Apurinic/Apyrimidinic Endonuclease 1-Dependent Regulation of Paired Box 8 Binding Activity. Antioxid Redox Signal. 2016 May 20; 24(15):855-66. (https://www.ncbi.nlm.nih.gov/pubmed/26908326) doi: 10.1089/ars.2014.6228
PUBMED DOIContenidos con Investigacion .
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Alfonso Luque Jiménez
Investigador Principal - Científico Titular
Código ORCID: 0000-0003-4022-0748
Tras la realización de mi Tesis de Licenciatura en la Universidad de Alcalá de Henares durante el año académico 1991-1992, en 1992 comencé mi Tesis Doctoral en la UCM, Madrid, sobre la regulación funcional de las moléculas de adhesión integrinas Beta1 en diferentes sistemas celulares, endoteliales e inmunes, y en varias situaciones fisiopatológicas.
A continuación, realicé un postdoctoral en el Hospital de La Princesa, Madrid, trabajando en la regulación funcional del ligando de la molécula de adhesión P-selectina denominado PSGL-1 durante la respuesta inflamatoria y migración transendotelial. En el 2000 me incorporé a un laboratorio de Investigación en Biología Vascular en UCLA, Los Ángeles, EE.UU. Participé en el estudio del mecanismo de acción del inhibidor de la angiogénesis tumoral ADAMTS1 y en la evaluación de animales integrinas beta 1 knockout endoteliales por el sistema cre-loxP.
En septiembre de 2005 me incorporé al CNIC, Madrid, con un contrato de Investigador Ramón y Cajal para estudiar el papel de la quinasa ILK en la regulación de la activación endotelial durante la respuesta inflamatoria y en proyectos relacionados con la funcionalidad del gen supresor de tumores ARF en la regulación de la respuesta inmune innata. Entre 2011-2013 estuve trabajando en el Hospital Niño Jesús, Madrid, en un proyecto relacionado con el papel del sistema inmune en enfermedades pediátricas y en el CISA-INIA, Valdeolmos-Madrid, en la caracterización de los linfocitos B y el sistema endotelial de un nuevo modelo animal de trucha.
En el 2013 me incorporé como Investigador Miguel Servet y en octubre de 2016 como Investigador Distinguido en el IIER-ISCIII, Majadahonda, Madrid, participando en estudios de la regulación de la polarización de macrófagos y funcionalidad endotelial. En mayo del 2021, me incorporé a la UFIEC-ISCIII y he constituido la Unidad de Endotelio Funcional.
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