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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
The C-terminus of H-Ras as a target for the covalent binding of reactive compounds modulating Rasdependent pathways
Oeste CL, Díez-Dacal B, Bray F, García de Lacoba M, de la Torre BG, Andreu D, Ruiz-Sánchez AJ, Pérez-Inestrosa E, García-Domínguez CA, Rojas, JM & Pérez-Sala D. The C-terminus of H-Ras as a target for the covalent binding of reactive compounds modulating Rasdependent pathways. PloS ONE. 2011; 6(1): e15866. doi:10.1371/journal.pone.0015866
DOINetrin-1 in Glioblastoma Neovascularization: The New Partner in Crime?
Vásquez X, Sánchez-Gómez P*, Palma V*. (* Co-corresponding author) (2021) Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime? Int J Mol Sci. 2021 Jul 31;22(15):8248. PMID: 34361013 doi: 10.3390/ijms22158248.
DOIValidation of dynamic risk stratification and impact of BRAF in risk assessment of thyroid cancer, a nation-wide multicenter study
Perez-Fernandez L, Sastre-Marcos J, Zafón C, Oleaga A, Castelblanco E, Capel I, Galofré JC, Guadalix S, De la Vieja A, and Riesco-Eizaguirre G*. Validation of dynamic risk stratification and impact of BRAF in risk assessment of thyroid cancer, a nation-wide multicenter study. Frontiers in Endocrinology 2023. 13:1071775. doi: 10.3389/fendo.2022.1071775. PMID: 36714606.
PUBMED DOIIdentification of Clusterin as a Major ABri- and ADan-Binding Protein Using Affinity Chromatography
Rostagno A, Calero M, Ghiso J. Identification of Clusterin as a Major ABri- and ADan-Binding Protein Using Affinity Chromatography. Methods Mol Biol. 2022 2466:49-60. doi: 10.1007/978-1-0716-2176-9_4.
DOIListe I Amyloid Precursor Protein (APP) Regulates Gliogenesis and Neurogenesis of Human Neural Stem Cells by Several Signaling Pathways
Coronel R, Bernabeu-Zornoza A, Palmer C, González R, Mateos P, Rosca A., Lopez-Alonso V, Liste I Amyloid Precursor Protein (APP) Regulates Gliogenesis and Neurogenesis of Human Neural Stem Cells by Several Signaling Pathways, Int J Mol Sci. 2023: 24(16):12964. Q1.
Molecular effects of polystyrene nanoplastics on human neural stem cells
Martin-Folgar, R.; González-Caballero, M.C.; Torres-Ruiz, M.; Cañas-Portilla, A.I.; de Alba-González, M.; Liste, I.; Morales, M. (2024). Molecular effects of polystyrene nanoplastics on human neural stem cells. PLoS One. 19, e0295816. doi: 10.1371/journal.pone.0295816.
DOIComparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis
González-García C, Bravo B, Ballester A, Gómez-Pérez R, Eguiluz C, Redondo M, Martínez A, Gil C and Ballester S. Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis British Journal of Pharmacology (2013) 170-3, pp.602-613. PMCID: PMC3791998 doi:10.1111/bph.12308
PUBMED DOILactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients
Bartolomé F, Rosa L, Valenti P, Lopera F, Hernández-Gallego J, Cantero JL, Orive G, Carro E. Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients. Front Immunol. 2022 Apr 25;13:878201. doi: 10.3389/fimmu.2022.878201
DOIClinical and cellular consequences of the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)
Clinical and cellular consequences of the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN). Martín Jiménez, R.; Martín Hernández, E.; Cabello, A.;García Silva, MT.; Arenas, J.; Campos, Y. 2012. Mitochondrion. 12: 288-293. DOI: 10.1016/j.mito.2011.10.004
DOIStructural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase
Dubach VRA, San Segundo-Acosta P, Murphy BJ. Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase. Nature Structural & Molecular Biology. 2024
DOI,9-dehydrohispanolone-15,16-lactol diterpene prevents LPS-triggered inflammatory response by inhibiting endothelial activation
L Jiménez-García; PG Través; R López-Fontal; S Herranz; MA Higueras; B de las Heras; S Hortelano; A Luque. 2016. 8,9-dehydrohispanolone-15,16-lactol diterpene prevents LPS-triggered inflammatory response by inhibiting endothelial activation. Biochem J. 2016 Jul 15;473(14):2061-71. https://doi.org/10.1042/BCJ20160343.
DOIEffects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells
Effects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells. Sandoval L, Rosca A, Oniga A, Zambrano A, Ramos JJ, González MC, Liste I, Motas M. Sci Total Environ. 2019 Sep 15;683:445-454. doi: 10.1016/j.scitotenv.2019.05.270. Epub 2019 May 20. PMID: 31136966
PUBMED DOISprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids
García-Domínguez CA, Martínez N, Gragera T, Pérez-Rodríguez A, Retana D, León G, Sánchez A, Oliva JL, Pérez-Sala D & Rojas JM. Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids. PloS ONE. 2011; 6(2): e16787. doi:10.1371/journal.pone.0016787
DOITumor-derived pericytes driven by EGFR mutations govern the vascular and immune microenvironment of gliomas
Segura-Collar B, Garranzo-Asensio M, Herranz B, Hernández-SanMiguel E, Cejalvo T, Casas BS, Matheu A, Pérez-Núñez Á, Sepúlveda-Sánchez JM, Hernández-Laín A, Palma V, Gargini R, Sánchez-Gómez P. (2021) Tumor-derived pericytes driven by EGFR mutations govern the vascular and immune microenvironment of gliomas. Cancer Res. 81(8):2142-2156. PMID: 33593822 doi: 10.1158/0008-5472.CAN-20-3558
DOIBasolateral sorting of the sodium iodide symporter (NIS) is mediated by AP-1 clathrin adaptor complexes
Koumarianou P, Fernández-Méndez C, Mielu LM, Fajardo-Delgado D, Santisteban P* and De la Vieja A*. Basolateral sorting of the sodium iodide symporter (NIS) is mediated by AP-1 clathrin adaptor complexes. Thyroid 2022. doi: 10.1089/thy.2022.0163. PMID: 35833460. NOTA: Artículo seleccionado para portada de la revista.
PUBMED DOIIntensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi
Anzibar Fialho M, Vázquez Alberdi L, Martínez M, Calero M, Baranger J, Tanter M, Damián JP, Negreira C, Rubido N, Kun A, Brum J. Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi. Sci Rep. 2022 12(1):6784. doi: 10.1038/s41598-022-10457-9. Erratum in: Sci Rep. 2022 10;12(1):7626.
DOIAge-dependent nasal immune responses in non-hospitalized bronchiolitis children
Cortegano I, Rodriguez M, Hernan-Gomez S, Arrabal A, Garcia-Vao C, Rodriguez J, et al. Age-dependent nasal immune responses in non-hospitalized bronchiolitis children. Front Immunol. 2022;13:1011607. Q1.
Low levels of amyloid precursor protein (APP) promote neurogenesis and decrease gliogenesis in human neural stem cells
Coronel, R.; López-Alonso, V.; Gallego, M.I.; Liste, I. (2023). Low levels of amyloid precursor protein (APP) promote neurogenesis and decrease gliogenesis in human neural stem cells. Int J Mol Sci. 24, 14635. doi: 10.3390/ijms241914635.
DOICombined use of pharmacophoric models together with drug metabolism and genotoxicity "in silico" studies in the hit finding process
Jerez MJ, Jerez M, González-García C, Ballester S and Castro A. Combined use of pharmacophoric models together with drug metabolism and genotoxicity "in silico" studies in the hit finding process. Journal of Computer-Aided Molecular Design (2013) 27-1, pp.79-90. ISSN 1573-4951 doi:10.1007/s10822-012-9627-1
PUBMED DOIDisturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
Carrero L, Antequera D, Alcalde I, Megías D, Figueiro-Silva J, Merayo-Lloves J, Municio C, Carro E. Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease. Acta Neuropathol Commun. 2023 Mar 31;11(1):55. doi: 10.1186/s40478-023-01529-6.
DOIAn HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation
Bonfiglio JJ, Leidecker O, Dauben H, Longarini EJ, Colby T, San Segundo-Acosta P, Perez KA, Matic I. An HPF1/PARP1-Based Chemical Biology Strategy for Exploring ADP-Ribosylation. Cell. 2020; 183:1086-1102.e23.
DOIRegulation of endothelial dynamics by PGC-1alpha relies on ROS control of VEGF-A signaling Free Radic Biol Med
I Prieto; C Sánchez-Ramos; A Luque; E Arza; Y Olmos; M Monsalve. (3/6). 2016. Regulation of endothelial dynamics by PGC-1alpha relies on ROS control of VEGF-A signaling Free Radic Biol Med. 2016 Apr;93:41-51. https://doi.org/10.1016/j.freeradbiomed.2016.01.021
DOIEarly induction of senescence and immortalization in PGC-1α-deficient mouse embryonic fibroblasts
Early induction of senescence and immortalization in PGC-1α-deficient mouse embryonic fibroblasts. Prieto I, Zambrano A, Laso J, Aranda A, Samper E, Monsalve M. Free Radic Biol Med. 2019 Jul;138:23-32. doi: 10.1016/j.freeradbiomed.2019.04.015. Epub 2019 Apr 25. PMID: 31029787.
PUBMED DOISos GEFs: old concepts and new perspectives
Rojas JM, Oliva JL & Santos E. Mammalian Sos GEFs: old concepts and new perspectives. Genes & Cancer. 2011; 2: 298-305. doi: 10.1177/1947601911408078
DOIBlood-Brain Barrier Disruption: A Common Driver of Central Nervous System Diseases
Segura-Collar B, Mata-Martínez P, Hernández-Laín A, Sánchez-Gómez P*, Gargini R*. (* co-corresponding) (2021) Blood-Brain Barrier Disruption: A Common Driver of Central Nervous System Diseases. The Neuroscientist. Jan 15: 1073858420985838. PMID: 33446074 doi: 10.1177/1073858420985838
DOIMesenchymal Stem Cells delivery in individuals with different pathologies. Multimodal tracking, safety and future applications
Belmar-López C, Vassaux G, Medel-Martinez A, Burnet J, Quintanilla M, Ramón Y Cajal S, Hernandez-Losa J, De la Vieja A*, and Martin-Duque P*. Mesenchymal Stem Cells delivery in individuals with different pathologies. Multimodal tracking, safety and future applications. International Journal of Molecular Sciences 2022 Jan 31;23(3):1682. doi: 10.3390/ijms23031682. PMID: 35163605
PUBMED DOICurcumin and Ethanol Effects in Trembler-J Schwann Cell Culture
Vázquez Alberdi L, Rosso G, Velóz L, Romeo C, Farias J, Di Tomaso MV, Calero M, Kun A. Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture. Biomolecules. 2022 12(4):515. doi: 10.3390/biom12040515.
DOITelomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data
Al Khleifat A, Iacoangeli A, Jones AR, van Vugt J, Moisse M, Shatunov A, et al. Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data. Front Cell Neurosci. 2022;16:1050596. Q1.
Amyloid precursor protein (APP) regulates gliogenesis and neurogenesis of human neural stem cells by several signaling pathways
Coronel, R.; Bernabeu-Zornoza, A.; Palmer, C.; González-Sastre, R.; Rosca, A.; Mateos-Martínez, P.; López-Alonso, V.; Liste, I. (2023). Amyloid precursor protein (APP) regulates gliogenesis and neurogenesis of human neural stem cells by several signaling pathways. Int J Mol Sci. 24, 12964. doi: 10.3390/ijms241612964.
DOIIntraepithelial paracrine Hedgehog signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland
García-Zaragoza, E.; Pérez-Tavarez, R.; Ballester, A.; Lafarga, V.; Jiménez- Reinoso, A.; Jiménez-Reinoso, A.; Ramírez, A.; Murillas, R. and Gallego, M.I. Intraepithelial paracrine Hedgehog signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland. Dev. Biol. (2012) 372-1, pp.28-44. PMID: 23000969 doi:10.1016/j.ydbio.2012.09.005
PUBMED DOIAltered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
Carrero L, Antequera D, Alcalde I, Megias D, Ordoñez-Gutierrez L, Gutierrez C, Merayo-Lloves J, Wandosell F, Municio C, Carro E. Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina. Int J Mol Sci. 2023 Oct 27;24(21):15679. doi: 10.3390/ijms242115679.
DOITelomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data
Al Khleifat A, Iacoangeli A, Jones AR, van Vugt J, Moisse M, Shatunov A, et al. Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data. Front Cell Neurosci. 2022;16:1050596. Q1.
Intersectin 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
DOIEuropean mitochondrial DNA haplogroups and liver fibrosis in HIV and hepatitis C virus coinfected patients
European mitochondrial DNA haplogroups and liver fibrosis in HIV and hepatitis C virus coinfected patients. García-Álvarez M, Guzmán-Fulgencio M, Berenguer J, Micheloud D, Campos Y, López JC, Cosín J, Miralles P, Alvarez E, Resino S. AIDS. 2011;25:1619-926. DOI: 10.1097/QAD.0b013e328349820f
DOIEuropean mitochondrial DNA haplogroups and metabolic disorders in HIV/HCV-coinfected patients on highly active antiretroviral therapy
European mitochondrial DNA haplogroups and metabolic disorders in HIV/HCV-coinfected patients on highly active antiretroviral therapy. Micheloud D, Berenguer J, Guzmán-Fulgencio M, Campos Y, García-Álvarez M, Catalán P, Cosín J, Miralles P, López JC, Resino S.J Acquir Immune Defic Syndr. 2011 ; 58:371-8. DOI: 10.1097/QAI.0b013e31822d2629
DOIMultiplexed monitoring of a novel autoantibody diagnostic signature of colorectal cancer using HaloTag technology-based electrochemical immunosensing platform
Garranzo-Asensio M, Guzmán-Aránguez A, Povedano E, Ruiz-Valdepeñas Montiel V, Poves C, Fernandez-Aceñero MJ, Montero-Calle A, Solís-Fernández G, Fernandez-Diez S, Camps J, Arenas M, Rodríguez-Tomàs E, Joven J, Sanchez-Martinez M, Rodriguez N, Dominguez G, Yáñez-Sedeño P, Pingarrón JM, Campuzano S, Barderas R. Multiplexed monitoring of a novel autoantibody diagnostic signature of colorectal cancer using HaloTag technology-based electrochemical immunosensing platform. Theranostics 2020; 10(7):3022-3034.
DOITumor suppressor ARF regulates tissue microenvironment and tumorgrowth through modulation of macrophage polarization Oncotarget
L Jiménez-García; S Herranz; MA Higueras; (AC); A Luque; S Hortelano. 2016. Tumor suppressor ARF regulates tissue microenvironment and tumorgrowth through modulation of macrophage polarization Oncotarget. 2016 Oct 11;7(41):66835-66850. https://doi.org/10.18632/oncotarget.11652.
DOIAβ42 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 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
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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