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Investigación
Patología Mitocondrial y ELA
Líneas de investigación
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Biotecnología de Células Troncales y Organoides
a) Generación de organoides del tracto respiratorio (minipulmones) a partir de células troncales pluripotentes humanas: embrionarias (hESCs) e inducidas (hiPSCs).
b) Modelización de enfermedades representativas de fibrosis pulmonar de los conductos aéreos y del parénquima pulmonar mediante minipulmones: Fibrosis Pulmonar Idiopática (FPI), Fibrosis Quística (FQ), Enfermedad Pulmonar Obstructiva Crónica (EPOC), etc.
c) Análisis del daño genómico y de la senescencia celular prematura y programada en el contexto de las enfermedades de interés.
d) Terapias avanzadas para enfermedades fibrosantes humanas, basadas en nuevos antifibróticos pertenecientes a la superfamilia de los receptores nucleares o con dianas en las rutas de señalización del daño genómico y de la senescencia celular.
e) Modelización de enfermedades de origen infeccioso mediante minipulmones y minihígados.
Proyectos de investigación
Content with Investigacion .
Generación de minipulmones a partir de células troncales pluripotentes embrionarias humanas: modelización de enfermedades respiratorias. 01/01/2020 hasta 31/12/2022. ISCIII-AESI 2019 (PI19CIII/00003; UFIECPY 498/19). Investigador Principal.
Influencia del VRSH en daño genómico y senescencia celular. 31/12/2015 hasta 31/12/2018. ISCIII-AESI 2015 (PI15CIII/00035; MPY 1146/16). Investigador Principal.
Exploring the potential therapeutic use of prosenescence and antisenescence compounds for the disease caused by HRSV. (CTA Pfizer) 2015-2017. Investigador Principal.
Regulación transcripcional de la respuesta inflamatoria por el VRSH. 31/12/2013 hasta 31/12/2017. ISCIII-FIS (MPY 1038/14). Investigador Principal. Investigador Principal.
Publicaciones destacadas
Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis
Solís-Fernández G, Montero-Calle A, Martínez-Useros J, López-Janeiro Á, de los Ríos V, Sanz R, Dziakova J, Milagrosa E, Fernández-Aceñero MJ, Peláez-García A, et al. Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis. Cells. 2022; 11(3):447
DOIPKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability
Martínez N, Gragera T, de Lucas MP, Cámara AB, Ballester A, Anta B, Fernández-Medarde A, López-Briones T, Ortega J, Peña-Jiménez D, Barbáchano A, Montero-Calle A, Cordero V, Barderas R, Iglesias T, Yunta M, Oliva JL, Muñoz A, Santos E, Zarich N & Rojas-Cabañeros JM. PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability. Oncogenesis. 2023; 12:20. doi.org/10.1038/s41389-023-00465-3
DOIApplied mathematics and nonlinear sciences in the war on cancer
Pérez-García VM, Fitzpatrick S, Pérez-Romasanta LA, Pesic M, Schucht P, Arana E, Sánchez-Gómez P. (2016) Applied mathematics and nonlinear sciences in the war on cancer. App. Math. Nonlin. Sci. 1(2): 423–436 doi: 10.21042/AMNS.2016.2.00036
DOInull
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. (*co-corresponding authors) (IF: 6,337)
PUBMED 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. 2021 144:108041. doi: 10.1016/j.bioelechem.2021.108041.
DOIThe project MinE databrowser: bringing large-scale whole-genome sequencing in ALS to researchers and the public
van der Spek RAA, van Rheenen W, Pulit SL, Kenna KP, van den Berg LH, Veldink JH, et al. The project MinE databrowser: bringing large-scale whole-genome sequencing in ALS to researchers and the public. Amyotroph Lateral Scler Frontotemporal Degener. 2019,20(5-6):432-40. Q1
Physiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved
Coronel, R.; Palmer, C.; Bernabeu-Zornoza, A.; Monteagudo, M.; Rosca, A.; Zambrano, A.; Liste, I. (2019). Physiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved. Neural Regen Res. 14, 1661-1671. doi: 10.4103/1673-5374.257511.
DOISalivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging
Reseco L, Atienza M, Fernandez-Alvarez M, Carro E, Cantero JL. Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging. Alzheimers Res Ther. 2021 Sep 6;13(1):150. doi: 10.1186/s13195-021-00891-8.
DOIBrain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis
Torres Iglesias G, Fernández-Fournier M, Botella L, Piniella D, Laso-García F, Gómez-de Frutos MC, Chamorro B, Puertas I, Tallón Barranco A, Fuentes B, de Leciñana MA, Alonso-López E, Bravo SB, Miranda-Carús ME, Montero-Calle A, Barderas R, Díez-Tejedor E, Gutiérrez-Fernández M, Otero-Ortega L. Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis. Brain, Behavior, and Immunity. 2023; 113:44
DOIPreclinical test of dacomitinib, an irreversible EGFR inhibitor, confirms its effectiveness for glioblastoma
Zahonero C, Aguilera P, Ramírez-Castillejo C, Pajares M, Bolós MV, Cantero C, Pérez-Núñez A, Hernández-Laín A, Sánchez-Gómez P*, Sepúlveda JM*. (*Co-corresponding authors) (2015) Preclinical test of dacomitinib, an irreversible EGFR inhibitor, confirms its effectiveness for glioblastoma. Mol. Can. Ther. 14(7):1548-58. PMID: 25939761 doi: 10.1158/1535-7163.MCT-14-0736
DOIInsulin drives glucose-dependent insulinotropic peptide expression via glucose-dependent regulation of FoxO1 and LEF1/β-catenin
García-Martínez JM, Chocarro-Calvo A, De la Vieja A, García-Jiménez C. Insulin drives glucose-dependent insulinotropic peptide expression via glucose-dependent regulation of FoxO1 and LEF1/β-catenin. Biochim Biophys Acta. 2014 Nov; 1839(11):1141-50. (https://www.ncbi.nlm.nih.gov/pubmed/25091498) doi:10.1016/j.bbagrm.2014.07.020
PUBMED DOIImpaired glucose metabolism reduces the neuroprotective action of adipocytokines in cognitively normal older adults with insulin resistance
Lopez-Vilaret KM, Cantero JL, Fernandez-Alvarez M, Calero M, Calero O, Lindín M, Zurrón M, Díaz F, Atienza M. Impaired glucose metabolism reduces the neuroprotective action of adipocytokines in cognitively normal older adults with insulin resistance. Aging (Albany NY). 2021 13(21):23936-23952. doi: 10.18632/aging.203668.
DOIWhole-Genome Sequences of Seven Listeria monocytogenes Strains from Different Stages of a Poultry Meat Production Chain
Lopez-Alonso V, Ortiz S, Martinez-Suarez JV. Whole-Genome Sequences of Seven Listeria monocytogenes Strains from Different Stages of a Poultry Meat Production Chain. Microbiol Resour Announc. 2019,8(11). Q4
Role 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. (2018). Role of amyloid precursor protein (APP) and its derivatives in the biology and cell fate specification of neural stem cells. Mol Neurobiol. 55, 7107-7117. doi: 10.1007/s12035-018-0914-2.
DOIStandardizing salivary lactoferrin measurements to obtain a robust diagnostic biomarker for Alzheimer's disease
Bartolome F, Orive G, Carro E. Standardizing salivary lactoferrin measurements to obtain a robust diagnostic biomarker for Alzheimer's disease. Alzheimers Dement (Amst). 2021 May 2;13(1):e12173. doi: 10.1002/dad2.12173.
DOIFlat clathrin lattices are linked to metastatic potential in colorectal cancer
Cresens C, Solís-Fernández G, Tiwari A, Nuyts R, Hofkens J, Barderas R, Rocha S. Flat clathrin lattices are linked to metastatic potential in colorectal cancer. iScience. 2023; 26: 107327
DOIControlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma
González-Gómez P, Crecente-Campo J, Zahonero C, de la Fuente M, Hernández-Laín A, Mira H*, Sánchez-Gómez P*, García-Fuentes M* (* Co-corresponding authors). (2015) Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma. Oncotarget, 6 (13): 10950-10963. PMID: 25860932 doi: 10.18632/oncotarget.3459
DOINIS mediates iodide uptake in the female reproductive tract and is a poor prognostic factor in ovarian cancer
Riesco-Eizaguirre G, Leoni SG, Mendiola M, Estévez-Cebrero MA, Gallego MI, Redondo A, Hardisson D, Santisteban P, De la Vieja A. NIS mediates iodide uptake in the female reproductive tract and is a poor prognostic factor in ovarian cancer. J Clin Endocrinol Metab. 2014 Jul; 99(7):E1199-208. (https://www.ncbi.nlm.nih.gov/pubmed/24708099) doi: 10.1210/jc.2013-4249
PUBMED DOIMedial Temporal Lobe Involvement in Human Prion Diseases: Implications for the Study of Focal Non Prion Neurodegenerative Pathology
Rábano A, Guerrero Márquez C, Juste RA, Geijo MV, Calero M. Medial Temporal Lobe Involvement in Human Prion Diseases: Implications for the Study of Focal Non Prion Neurodegenerative Pathology. Biomolecules. 2021 Mar 10;11(3):413. doi: 10.3390/biom11030413.
DOIAdvances in Alzheimer’s Disease Research: Human Cerebral Organoids
Mateos P., González R., Coronel R., Rosca A, Martín S., Bernabeu A, López-Alonso V and Liste I. Advances in Alzheimer’s Disease Research: Human Cerebral Organoids. American Journal of Biomedical Science & Research. 2023; 715:719.
Advances in Alzheimer’s disease research: Human cerebral organoids
Mateos-Martínez, P.; González-Sastre, R.; Coronel, R.; Rosca, A.; Martín-Benito, S.; Bernabeu-Zornoza, A.; López-Alonso, V.; Liste, I. (2023). Advances in Alzheimer’s disease research: Human cerebral organoids. Am J Biomed Sci & Res. 18, AJBSR.MS.ID.002421. doi: 10.34297/AJBSR.2023.18.002421.
DOIKynurenic Acid Levels are Increased in the CSF of Alzheimer's Disease Patients
González-Sánchez M, Jiménez J, Narváez A, Antequera D, Llamas-Velasco S, Martín AH, Arjona JAM, Munain AL, Bisa AL, Marco MP, Rodríguez-Núñez M, Pérez-Martínez DA, Villarejo-Galende A, Bartolome F, Domínguez E, Carro E. Kynurenic Acid Levels are Increased in the CSF of Alzheimer's Disease Patients. Biomolecules. 2020 Apr 8;10(4):571. doi: 10.3390/biom10040571.
DOIMultiomics Profiling of Alzheimer’s Disease Serum for the Identification of Autoantibody Biomarkers
San Segundo-Acosta P, Montero-Calle A, Jernbom-Falk A, Alonso-Navarro M, Pin E, Andersson E, Hellström C, Sánchez-Martínez M, Rábano A, Solís-Fernández G, Peláez-García A, Martínez-Useros J, Fernández-Aceñero MJ, Månberg A, Nilsson P, Barderas R. Multiomics Profiling of Alzheimer’s Disease Serum for the Identification of Autoantibody Biomarkers. Journal of Proteome Research 2021 20 (11), 5115-5130.
DOIEGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy
Zahonero C and Sánchez-Gómez P. (2014) EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy. Cel. Mol. Life Sci. 71 (18): 3465-88. PMID: 24671641 doi: 10.1007/s00018-014-1608-1
DOIWorking Group on Disorders Related to Iodine Deficiency and Thyroid Dysfunction of the Spanish Society of Endocrinology and Nutrition. Iodine supplementation during pregnancy and lactation. Position statement of the working group on disorders related to iodine deficiency and thyroid dysfunction of the Spanish Society of Endocrinology and Nutrition
Donnay S, Arena J, Lucas A, Velasco I, Ares S; Working Group on Disorders Related to Iodine Deficiency and Thyroid Dysfunction of the Spanish Society of Endocrinology and Nutrition.. Iodine supplementation during pregnancy and lactation. Position statement of the working group on disorders related to iodine deficiency and thyroid dysfunction of the Spanish Society of Endocrinology and Nutrition. Endocrinol Nutr. 2014 Jan; 61(1):27-34. (https://www.ncbi.nlm.nih.gov/pubmed/24035326) doi:10.1016/j.endonu.2013.05.004
PUBMED DOIValidation of a novel and accurate ApoE4 assay for automated chemistry analyzers
Veiga S, Rodríguez-Martín A, Garcia-Ribas G, Arribas I, Menacho-Román M, Calero M. Validation of a novel and accurate ApoE4 assay for automated chemistry analyzers. Sci Rep. 2020 10(1):2138. doi: 10.1038/s41598-020-58841-7.
DOIHuman neural stem cells in developmental neurotoxicology: Current scenario and future prospects. Alternative Methods in Neurotoxicology
Rosca A., Coronel R., López-Alonso V, Liste I, González-Caballero M. Carmen. Human neural stem cells in developmental neurotoxicology: Current scenario and future prospects. Alternative Methods in Neurotoxicology. Advances in Neurotoxicology. 2023; 197:226.
Treatment of Parkinson’s disease using human stem cells
Palmer, C.; Coronel, R.; Liste, I. (2016). Treatment of Parkinson’s disease using human stem cells. J Stem Cell Res Med. 1, 71-77. doi: 10.15761/JSCRM.1000113.
DOIAnnexin A5 prevents amyloid-β-induced toxicity in choroid plexus: implication for Alzheimer's disease
Bartolome F, Krzyzanowska A, de la Cueva M, Pascual C, Antequera D, Spuch C, Villarejo-Galende A, Rabano A, Fortea J, Alcolea D, Lleo A, Ferrer I, Hardy J, Abramov AY, Carro E. Annexin A5 prevents amyloid-β-induced toxicity in choroid plexus: implication for Alzheimer's disease. Sci Rep. 2020 Jun 10;10(1):9391. doi: 10.1038/s41598-020-66177-5.
DOIIn-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression
Montero-Calle A, López-Janeiro Á, Mendes ML, Perez-Hernandez D, Echevarría I, Ruz-Caracuel I, Heredia-Soto V, Mendiola M, Hardisson D, Argüeso P, Peláez-García A, Guzman-Aranguez A, Barderas R. In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression. Cell Oncol. 46, 697–715 (2023).
DOIDYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth
Pozo Zahonero, Fernández P, Liñares JM, Ayuso A, Hagiwara M, Pérez A, Ricoy JR, Hernández-Laín A, Sepúlveda JM, Sánchez-Gómez P. (2013) Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth. J. Clin. Invest. 123(6):2475-87. PMID: 23635774 doi: 10.1172/JCI63623
DOIA new link between diabetes and cancer: enhanced Wnt/beta-catening signaling by high glucose
García-Jiménez C, Garcia-Martinez JM, Chocarro-Calvo A, and De la Vieja A. A new link between diabetes and cancer: enhanced Wnt/beta-catening signaling by high glucose. Journal of Molecular Endocrinology 2014 52(1): R51-R66. (https://www.ncbi.nlm.nih.gov/pubmed/24049067) doi: 10.1530/JME-13-0152
PUBMED DOISpanish CJD Surveillance Group. Human prion disease surveillance in Spain, 1993-2018: an overview
De Pedro-Cuesta J, Almazán-Isla J, Tejedor-Romero L, Ruiz-Tovar M, Avellanal F, Rábano A, Calero M, García López FJ; Spanish CJD Surveillance Group. Human prion disease surveillance in Spain, 1993-2018: an overview. Prion. 2021. 15(1):94-106. doi: 10.1080/19336896.2021.1933873.
DOIGenetic Diversity, Antimicrobial Resistance and Survival upon Manure Storage of Campylobacter jejuni Isolated from Dairy Cattle Farms in the Cantabric Coast of Spain
Varsaki, A.; Ortiz, S.; Santorum, P.; López, P.; López-Alonso, V.; Martínez-Suárez, J.V. Genetic Diversity, Antimicrobial Resistance and Survival upon Manure Storage of Campylobacter jejuni Isolated from Dairy Cattle Farms in the Cantabric Coast of Spain. Zoonotic Dis. 2022, 2, 82–94
Pursuing precision in medicine and nutrition: the rise of electrochemical biosensing at the molecular level
Campuzano S, Barderas R, Moreno-Casbas MT, Almeida A. Pursuing precision in medicine and nutrition: the rise of electrochemical biosensing at the molecular level. Anal Bioanal Chem 416, 2151–2172 (2024)
DOIGlucose-Induced b-Catenin Acetylation Enhances Wnt Signaling in Cancer
Chocarro-Calvo A, Garcia-Martinez JM, Ardila-González S, De la Vieja A and García-Jiménez C*. Glucose-Induced b-Catenin Acetylation Enhances Wnt Signaling in Cancer. Molecular Cell 2013 49(3):474-486. PMID: 23273980. doi: 10.1016/j.molcel.2012.11.022
DOIAlzheimer’s Disease Neuroimaging Initiative. Long runs of homozygosity are associated with Alzheimer's disease
Moreno-Grau S, Fernández MV, de Rojas I, Garcia-González P, Hernández I, Farias F, Budde JP, Quintela I, Madrid L, González-Pérez A, Montrreal L, Alarcón-Martín E, Alegret M, Maroñas O, Pineda JA, Macías J; GR@ACE study group; DEGESCO consortium, Marquié M, Valero S, Benaque A, Clarimón J, Bullido MJ, García-Ribas G, Pástor P, Sánchez-Juan P, Álvarez V, Piñol-Ripoll G, García-Alberca JM, Royo JL, Franco-Macías E, Mir P, Calero M, Medina M, Rábano A, Ávila J, Antúnez C, Real LM, Orellana A, Carracedo Á, Sáez ME, Tárraga L, Boada M, Cruchaga C, Ruiz A; Alzheimer’s Disease Neuroimaging Initiative. Long runs of homozygosity are associated with Alzheimer's disease. Transl Psychiatry. 2021 11(1):142. doi: 10.1038/s41398-020-01145-1.
DOIEndothelial-specific deficiency of megalin in the brain protects mice against high-fat diet challenge
Bartolome F, Antequera D, de la Cueva M, Rubio-Fernandez M, Castro N, Pascual C, Camins A, Carro E. Endothelial-specific deficiency of megalin in the brain protects mice against high-fat diet challenge. J Neuroinflammation. 2020 Jan 14;17(1):22. doi: 10.1186/s12974-020-1702-2.
DOIExperimental Radiation System for Effects Assessment in Biological in Vitro and in Vivo Models
V. Ramos, P. Marina, M. Torres-Ruiz, O. J. Suárez, V. López, I. Liste, M. de Alba. "Experimental Radiation System for Effects Assessment in Biological in Vitro and in Vivo Models," 2021 Photonics & Electromagnetics Research Symposium (PIERS), 2021, pp. 2800-2807, doi: 10.1109/PIERS53385.2021.9695112
DOIp53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins
Montero-Calle A, Garranzo-Asensio M, Torrente-Rodríguez RM, Ruiz-Valdepeñas Montiel V, Poves C, Dziaková J, Sanz R, Díaz del Arco C, Pingarrón JM, Fernández-Aceñero MJ, et al. p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins. Cancers. 2023; 15(7):2102.
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.