Memoria científica del Cima Universidad de Navarra. Curso 2020-21 by Clínica Universidad de Navarra

MEMORIA CIENTÍFICA 2020-2021 CIMA UNIVERSIDAD DE NAVARRA

CIMA

FACULTADES DE MEDICINA, CIENCIAS Y FARMACIA Y NUTRICIÓN

CLÍNICA UNIVERSIDAD DE NAVARRA

El Cima Universidad de Navarra es una institución biomédica de la Universidad de Navarra que apuesta por realizar una investigación traslacional de excelencia, basada en un conocimiento biológico novedoso y en una constante innovación en el desarrollo de nuevos fármacos y terapias.

Desde 2018 tiene la condición de Instituto de Investigación Universitario de la Universidad de Navarra. En este contexto, comparte su misión de servicio a los pacientes y a la sociedad, a través del trabajo excelente, la libertad, el respeto, la multidisciplinariedad, la responsabilidad, el servicio y la internacionalidad.

Su objetivo científico, como centro de investigación de la Clínica Universidad de Navarra, es afrontar problemas clínicos actuales y encontrar soluciones terapéuticas a las necesidades de los pacientes

El Cima colabora con profesionales del Hospital Universitario de Navarra, de Navarrabiomed y de la Universidad Pública de Navarra, en el marco del Instituto de Investigación Sanitaria de Navarra (IdiSNA), al que ha contribuido a constituir y acreditar.

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ÍNDICE Presentación: Carta de la directora 1. El Cima 1.1. Organigrama 1.2. Organización de la investigación (Programas y plataformas) 1.3. Profesionales: equipos multidisciplinares 1.4. Financiación 2. Actividad científica 2.1. Producción científica en datos 2.2. Publicaciones 2.3. Proyectos competitivos (nacionales e internacionales) 2.4. Eventos científicos 2.5. Sello de excelencia 3. Innovación y transferencia 3.1. Patentes y gestión de investigación 3.2. Transferencia de conocimiento 3.3. Otras alianzas con empresas e instituciones 4. Investigar para curar 4.1. Ensayos clínicos 4.2. Innovación frente a COVID Desarrollo de un prototipo de vacuna frente a SARS-CoV-2 Predicción de eficacia de la vacuna en pacientes hematológicos 4.3. Innovación en la investigación traslacional 5. Actividad docente 6. El Cima y sociedad 6.1. Acciones divulgativas 6.2. Amigos del Cima 6.3. Compromiso con la sociedad 6.4. El Cima en los medios

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1. PRESENTACIÓN Ahora que cerramos el curso 2020-2021, y a pesar de las dificultades que hemos tenido que afrontar con la pandemia, nos planteamos un nuevo horizonte de trabajo marcado por nuevos retos profesionales. Durante este tiempo, y al igual que otros centros tecnológicos y de investigación, el Cima ha impulsado proyectos científicos dirigidos específicamente a contribuir al desarrollo de terapias frente al COVID-19. En este sentido, el grupo de Inmunología e Inmunoterapia ha desarrollado un prototipo de vacuna frente a este virus cuya eficacia se ha confirmado en un modelo animal de la enfermedad, y ha dado lugar al registro de una patente. Por su parte, investigadores del Programa de Hemato-Oncología han liderado un estudio que ayuda a predecir la eficacia de vacunas contra el COVID-19 en pacientes hematológicos. El estudio de los biomarcadores inmunes de estos pacientes podría contribuir a predecir y mejorar la eficacia de las dosis que deben recibir. A pesar de la excepcionalidad de la situación, la actividad científica se ha adaptado a las circunstancias y se ha desarrollado sin contratiempos. Durante el año natural 2020 se publicaron más de 200 trabajos, 92% de los artículos originales se han publicado en revistas del primer cuartil de su especialidad. El 25% de ellos lo componen artículos que se encuentran en el 10% de los artículos más citados a nivel mundial. Se han solicitado 5 nuevas patentes generadas en el Cima y se han formalizado acuerdos con distintas empresas biotecnológicas por un importe superior a los 10 millones de euros. Todos estos datos vienen a reflejar el esfuerzo realizado por nuestros investigadores por seguir realizando una investigación de primera línea comprometida con la búsqueda de soluciones terapéuticas que puedan beneficiar a los pacientes. Muy destacada ha sido la redacción del plan estratégico del Cima 2021-2024. Los proyectos científicos que se proponen dentro de este documento están perfectamente alineados con la Estrategia 2025 de la Universidad de Navarra. Este trabajo se ha realizado con la participación de los investigadores del Cima y con una importante contribución del nuestro Comité Asesor externo a los que agradezco su dedicación y generosidad en esta tarea. En el contexto de este nuevo plan, se propone como objetivo para el nuevo periodo el impulso en terapias avanzadas, con un foco en el desarrollo de distintas estrategias de inmunoterapia y reforzando nuestra apuesta por la terapia génica. El objetivo fundamental de todos estos esfuerzos es la búsqueda de la excelencia en aquellas áreas en las que el Cima ya realiza un trabajo muy destacado. El curso ha terminado con la estupenda noticia de la concesión del Premio Nacional de Investigación en Medicina al Dr. Jesús San Miguel, Director Científico del Cima, por su importante aportación al conocimiento y tratamiento de enfermedades hematológicas, muy especialmente el mieloma. Mi enhorabuena a él y el agradecimiento por su trabajo incansable del que nos beneficiamos tantos. Me gustaría finalizar recordando que la investigación del Cima se apoya también en la ayuda de particulares, instituciones y fundaciones que en medio de enormes dificultades han continuado impulsándonos con su generosidad. Agradecemos también el compromiso y la confianza de las instituciones y agencias, públicas y privadas, que confían en nuestros proyectos de investigación. No vamos a defraudarles y afrontamos con más ilusión y empeño, si cabe, el reto que tenemos por delante para estar en el origen de la ciencia, abriendo nuevos caminos a los enfermos que nos esperan. Dra. Mª Pilar Civeira Murillo Directora general Cima Universidad de Navarra

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1. EL CIMA 1.1. Organigrama La Fundación para la Investigación Médica Aplicada (FIMA) es la entidad titular del Cima. Se rige por un patronato, dirigido por D. Enrique de Sendagorta. Miembros del Patronato: D. Jorge Lucaya (vicepresidente), D. Igor Errasti (secretario), D.ª Iciar Astiasarán (vocal), D. Miguel Sanz (vocal), D.ª Isabel Estapé (vocal). Miembros honoríficos: D. Antonio Catalán, D. Javier Olave y D. Antonio Trueba. Director de la Fundación: D. Francisco Errasti. I. Órganos de Gobierno del Cima a. Comité de Dirección: Dra. Mª Pilar Civeira, directora; Dr. Jesús San Miguel, director científico; Dra. Gloria González-Aseguinolaza, subdirectora; Dr. Antonio Pineda-Lucena, subdirector; D.ª María Mora, gerente, y Dra. Ana Fortuño, secretaria científica.

b. Consejo científico asesor: Dres. Matías Ávila, Rubén Pío, Felipe Prósper, Mª Cruz Rodríguez-Oroz, Arantxa González Miqueo, Cristian Smerdou, Juan José Lasarte, Carlos Ortiz de Solórzano, Antonio Pineda-Lucena, Bruno Paiva, Fernando Lecanda e Ignacio Melero, investigadores del Cima.

c. Comité científico externo: Dres. Vicente Vicente, catedrático de Medicina Interna de la Universidad de Murcia; Margarita Del Val, directora de la Unidad de Inmunología Viral del CSIC; Jean Charles Soria, director del Departamento de Desarrollo de Medicamentos del Centro del Cáncer Gustave Roussy Cancer Center de París, Ramón Bataller, director asociado del Centro de Investigación del Hígado de Pittsburgh (Estados Unidos), Gema Frühbeck, directora del Laboratorio de Investigación Metabólica de la Clínica Universidad de Navarra, Dr. Juan Bueren, responsable de la División de Terapias Innovadoras en el Sistema Hematopoyético del CIEMAT, Dr. Joaquín Castilla, investigador principal y profesor de Investigación de Ikerbasque (CIC bioGUNE - Bilbao) en el Laboratorio de Investigación de Priones y Dr. Ángel Carracedo, catedrático de Medicina Genómica de la Universidad de Santiago de Compostela.

II. El Cima es un Instituto de Investigación de la Universidad de Navarra, por aplicación del Art. 10 de la Ley Orgánica 6/2001, de 21 de diciembre, de Universidades.

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1.2. Organización de la investigación: programas y plataformas científicas La actividad investigadora del Cima se estructura en 5 programas verticales, 5 programas transversales, 10 plataformas y servicios técnicos de apoyo a la investigación, así como servicios de administración y gestión.

Este sólido modelo organizativo refuerza la colaboración funcional de equipos multidisciplinares que trabajan con un enfoque traslacional en el abordaje integral de las enfermedades que investiga.

ESTRUCTURA FUNCIONAL DEL CIMA

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PROGRAMAS VERTICALES

HEPATOLOGÍA

NEUROCIENCIAS

DIRECTOR Dr. Matías Ávila

DIRECTORA Dra. Mª Cruz Rodríguez-Oroz

Línea de investigación: 1. Daño hepático y carcinogénesis: 2. Porfirias agudas

Líneas de investigación: 1. Enfermedad de Alzheimer 2. Enfermedad de Parkinson 3. Esclerosis lateral amiotrófica (ELA)

TUMORES SÓLIDOS DIRECTOR Dr. Rubén Pío Líneas de investigación: 1. Biomarcadores y nuevas dianas terapéuticas en cáncer de pulmón 2. Oncologia traslacional. Cáncer de ovario 3. Avances en radioterapia 4. Modelos preclínicos y herramientas de análisis 5. Oncogenes y dianas efectoras. Cáncer de páncreas 6. Terapias avanzadas para tumores sólidos pediátricos

HEMATO-ONCOLOGÍA DIRECTORES Dres. Jesús San Miguel y Felipe Prósper Líneas de investigación: 1. Mieloma múltiple 2. Patología mieloide 3. Síndromes linfoproliferativos 4. Terapia celular adoptiva (CAR-T)

ENFERMEDADES CARDIOVASCULARES DIRECTOR Dra. Arantxa González Miqueo Líneas de investigación: 1. Insuficiencia cardíaca 2. Aterotrombosis

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PROGRAMAS TRANSVERSALES

INMUNOLOGÍA E INMUNOTERAPIA

MEDICINA REGENERATIVA

DIRECTOR Dr. Juan José Lasarte

DIRECTOR Dr. Felipe Prósper

Líneas de investigación: 1. Inmunomodulación y microambiente tumoral 2. Estrategias combinadas de inmunoterapia traslacional 3. Terapias basadas en citoquinas 4. Terapia celular adoptiva (TIL) 5. Desarrollo de vacunas

Líneas de investigación: 1. Fabricación aditiva e ingeniería de tejidos 2. Xeno-órganos 3. Estrategias de reprogramación cardíaca 4. Terapias regenerativas en enfermedades músculo-esqueléticas

TERAPIAS MOLECULARES TERAPIA GÉNICA Y REGULACIÓN DE LA EXPRESIÓN GÉNICA

DIRECTOR Dr. Antonio Pineda-Lucena

DIRECTOR Dr. Cristian Smerdou

Líneas de investigación: 1. Química médica 2. Aptámeros 3. Péptidos

Líneas de investigación: 1. Terapia génica: Aplicación en cáncer y enfermedades monogénicas 2. Expresión génica: ARN no codificante, regulación del genoma del cáncer y papel del estrés del retículo

BIOLOGÍA COMPUTACIONAL DIRECTOR Dr. Mikel Hernáez Líneas de investigación: 1. Análisis de datos transcriptómicos 2. Desarrollo de nuevos formatos de archivo para almacenar y acceder a datos ómicos.

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PLATAFORMAS DE APOYO A LA INVESTIGACIÓN

BIOBANCO

GENÓMICA

RESPONSABLE Dra. Mª Antonia Fortuño

RESPONSABLE Dr. Josep María Argemí

Actúa de nexo de unión entre donantes, clínicos e investigadores con el propósito de asegurar un tratamiento seguro y eficaz de las muestras biológicas y datos asociados.

Esta plataforma tiene como finalidad generar información genómica a partir de muestras biológicas, tanto clínicas como de experimentación. Para ello, dispone de un catálogo de tecnologías de última generación, que están a disposición de investigadores, pacientes y empresas.

MORFOLOGÍA RESPONSABLE Dra. Laura Guembe Tiene la finalidad de proporcionar a la comunidad científica un servicio especializado en el procesamiento de muestras histológicas. Durante el curso 2021 se han atendido 890 solicitudes.

PRODUCCIÓN Y EXPERIMENTACIÓN ANIMAL RESPONSABLE Dra. Elena Ciordia Da soporte a todos los proyectos de investigación de la Universidad de Navarra, Cima y Clínica Universidad de Navarra que requieran el uso de animales. En su laboratorio P3 se han realizado este año las pruebas de eficacia del prototipo de vacuna frente a COVID-19 desarrollado en el Cima.

CITOMETRÍA RESPONSABLE Dr. Bruno Paiva La citometría de flujo es una técnica esencial para el diagnóstico diferencial, clasificación pronóstica, y monitorización de enfermedad mínima residual (EMR) en múltiples neoplasias hematológicas. Además, el potencial de la citometría para detectar y caracterizar un número reducido de células resulta cada vez más atractivo para monitorizar también los tumores sólidos. En 2021 los investigadores de esta plataforma han descubierto los mecanismos de resistencia al tratamiento en pacientes con mieloma múltiple de alto riesgo.

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PLATAFORMAS DE APOYO A LA INVESTIGACIÓN

BIOINFORMÁTICA

INSTALACIÓN RADIACTIVA

RESPONSABLE Dr. Mikel Hernáez

RESPONSABLE Dra. Lourdes Ortiz

Gracias a los datos provenientes de la experimentación en proteómica, la plataforma de bioinformática facilita la identificación de biomarcadores o de nuevas dianas terapéuticas para el desarrollo de medicamentos. Asimismo, impulsa el desarrollo de cualquier estudio de DNA/RNA a escala masiva, bien sea en humanos o en otros organismos.

Supervisa la utilización de productos radiactivos y equipos emisores de radiaciones ionizantes, fundamentales para el desarrollo de las líneas de investigación que se llevan a cabo en nuestro centro de investigación, de acuerdo con la normativa vigente establecida por el Consejo de Seguridad Nuclear.

IMAGEN

ANÁLISIS BIOQUÍMICOS Y METABOLISMO CELULAR

RESPONSABLE Dr. Carlos Ortiz de Solórzano

RESPONSABLE Dra. Eva Santamaría

Proporciona un servicio de adquisición y análisis cuantitativo de imagen microscópica y de imagen no invasiva en animales de laboratorio.

Gracias a tecnología de vanguardia analiza múltiples parámetros bioquímicos en muestras de suero, plasma u orina, y estudia el metabolismo y la bioenergética celular a tiempo real.

PLATAFORMA DE MICRO-PET RESPONSABLE Dr. Iván Peñuelas La PET (Positron Emission Tomography) es una técnica de imagen molecular in vivo que permite visualizar y cuantificar una gran cantidad de procesos biológicos y fisiológicos. El Micro-PET aplica esta técnica al estudio de pequeños animales. Al tener un carácter no invasivo permite el seguimiento longitudinal del animal a lo largo de todo el proceso experimental.

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SERVICIOS DE ADMINISTRACIÓN Y GESTIÓN La actividad investigadora del Cima se gestiona a través de una gerencia y distintos departamentos como dirección financiera y administrativa, la Unidad de Traslación e Innovación y Servicios Generales, que reciben el apoyo de Comunicación y Desarrollo Institucional o Fundraising.

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423

PROFESIONALES

1.3. Profesionales: equipos multidisciplinares En el Cima trabajan 423 profesionales.

68 INVESTIGADORES

104

132

38 INVESTIGADORES POSTDOCTORALES

41 INVESTIGADORES EN FORMACIÓN (ESTUDIANTES PREDOCTORALES)

PERSONAL TÉCNICO DE INVESTIGACIÓN

PERSONAL DE ADMINISTRACIÓN Y GESTIÓN

40 OTRAS CATEGORÍAS

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1.4. Financiación

El presupuesto destinado a la investigación durante este año ha sido de: 20.900.000 € Su financiación se obtiene de 3 pilares fundamentales: - Acuerdos de colaboración: 41,00% - Proyectos competitivos nacionales e internacionales: 32% - Aportaciones sin ánimo de lucro de particulares, empresas y fundaciones: 27%

3.000.000 €

IMPORTE TOTAL OBTENIDO DE FUNDRAISING Y MECENAZGO

Aportaciones sin ánimo de lucro de particulares, empresas y fundaciones 27,00%

Proyectos competitivos nacionales e internacionales 32,00%

Acuerdos de colaboración 41,00%

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FUENTES DE FINANCIACIÓN DEL CIMA ACUERDOS DE COLABORACIÓN, 41,00% PROYECTOS COMPETITIVOS NACIONALES, 32,00% APORTACIONES DE PARTICULARES Y FUNDACIONES, 27,00%

ANTONIO CATALÁN Presidente de AC Hotels

FUNDACIÓN FUENTES DUTOR

FUNDACIÓN CULTURA Y ASISTENCIA

AGANSA S.L.

FUNDACIÓN ECHÉBANO

ALFREDO MAHOU

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2. ACTIVIDAD CIENTÍFICA 2.1. Producción científica en datos Durante el año 2020 la actividad científica del Cima ha dado lugar a 247 publicaciones. 210 en primer cuartil Factor de impacto medio 8.624 Factor de impacto medio con autoría 9.099

247

PUBLICACIONES

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9,10

FACTOR DE IMPACTO MEDIO DE PUBLICACIONES CON AUTORÍA DEL CIMA

PUBLICACIONES EN REVISTAS DE ALTO IMPACTO

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2.2. Publicaciones Selección de publicaciones destacadas en 2020 1. Givosiran - Running RNA Interference to Fight Porphyria Attacks. Gonzalez-Aseguinolaza, G. New England Journal of Medicine. 2020 Jun 11;382(24):2366-2367. doi: 10.1056/NEJMe2010986. Programa de Terapia Génica y Regulación de la Expresión Génica Primer decil Top 3

5. Endogenous retroelement activation by epigenetic therapy reverses the Warburg effect and elicits mitochondrial-mediated cancer cell death. Fresquet V et al. Cancer Discovery. 2021 May;11(5):1268-1285. doi: 10.1158/2159-8290.CD-20-1065. Epub 2020 Dec 18. Programa de Hemato-oncología Primer decil

2. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, openlabel, phase 3 trial. Mateos, MV et al. Lancet. 2020 Jan 11;395(10218):132-141. doi: 10.1016/ S0140-6736(19)32956-3. Epub 2019 Dec 10. Programa de Hematooncología Primer decil Top 3

6. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Teijeira, A et al. Immunity. 2020 May 19;52(5):856-871.e8. doi:10.1016/j.immuni.2020.03.001. Epub 2020 Apr 13. Programa de Inmunología e Inmunoterapia Primer decil Top 3

3. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors. Schalper, KA et al. Nature Medicine. 2020 May;26(5):688-692. doi: 10.1038/s41591-020-0856-x. Epub 2020 May 11. Programa de Inmunología e Inmunoterapia Primer decil Top 3 4. Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma. Paiva, B et al. Journal of Clinical Oncology Vol. 38, No. 8, March 10, 2020 Programa de Hemato-oncología Primer decil

7. Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction. Ruiz-Villalba, A et al. Circulation. 2020 Nov 10; 142(19): 1831–1847. Programa de Medicina Regenerativa Primer decil Top 3 8. Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD). SaenzPipaon, et al. Journal of Extracellular Vesicles. 2020 Feb 19;9(1):1729646. doi: 10.1080/20013078.2020.1729646. eCollection 2020. Programa de Enfermedades Cardiovasculares Primer decil

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9. SMIM30, a tiny protein with a big role in liver cancer. Unfried, JP t al. Journal of Hepatology. 2020 Nov;73(5):1010-1012. doi: 10.1016/j.jhep.2020.07.015. Epub 2020 Aug 22 Programa de Terapia Génica y regulación de la expresión génica Primer decil Top 3 10. Myocardial Interstitial Fibrosis in Nonischemic Heart Disease. Diez, J et al. Journal of the American College of Cardiology. 2020 May 5;75(17):2204-2218. doi: 10.1016/j.jacc.2020.03.019. Programa de Enfermedades Cardiovasculares Primer decil 11. Recent advances in alcoholrelated liver disease (ALD): summary of a Gut round table meeting. Avila, MA et al. Gut. 2020 Apr;69(4):764-780. doi: 10.1136/gutjnl-2019-319720. Epub 2019 Dec 26. Programa de Hepatogía Primer decil

12. Liver Kinase B1 (LKB1) Loss Has its p-ERKs: ERK Inactivation as a Vulnerability in NSCLC With LKB1 Mutations. Macaya, I et al. Journal of Thoracic Oncology. 2020 Mar;15(3):311-313. doi: 10.1016/j. jtho.2019.11.017. Programa de Tumores Sólidos Primer decil 13. A IncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions. Grossi, E at al. Nature Communications. 2020 Feb 18;11(1):936. doi: 10.1038/s41467020-14623-3. Programa de Terapia Génica y Regulación de la Expresión Génica Primer decil 14. The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas. Valencia, K et al; Journal of Clinical Investigation. 2020 Apr 1; 130(4): 1879–1895. Programa de Tumores Sólidos Primer decil

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PUBLICACIONES POR PROGRAMAS

HEPATOLOGÍA Ancin, M; Sanz-Barrio, R; Santamaria, E; Fernandez-San Millan, A; Larraya, L; Veramendi, J; Farran, I. Functional Improvement of Human Cardiotrophin 1 Produced in Tobacco Chloroplasts by Co-Expression with Plastid Thioredoxin m. Plants (Basel). 2020 Feb 2;9(2):183. doi: 10.3390/ plants9020183. Article Arasanz, H; Hernandez, C; Bocanegra, A; Chocarro, L; Zuazo, M; Gato, M; Ausin, K; Santamaria, E; Fernandez-Irigoyen, J; Fernandez, G; Santamaria, E; Rodriguez, C; Blanco-Luquin, I; Vera, R; Escors, D; Kochan, G Arasanz, Hugo; Hernandez, Carlos; Bocanegra, Ana; Chocarro, Luisa; Zuazo, Miren; Gato, Maria; Ausin, Karina; Santamaria, Enrique; Fernandez-Irigoyen, Joaquin; Fernandez, Gonzalo; Santamaria, Eva; Rodriguez, Carlos; Blanco-Luquin, Idoia; Vera, Ruth; Escors, David; Kochan, Grazyna. Profound Reprogramming towards Stemness in Pancreatic Cancer Cells as Adaptation to AKT Inhibition. Cancers (Basel). 2020 Aug 5;12(8):2181. doi: 10.3390/cancers12082181. Article Arechederra, M; Berasain, C; Avila, MA; FernandezBarrena, MG. Chromatin dynamics during liver regeneration. Semin Cell Dev Biol. 2020 Jan;97:3846. doi: 10.1016/j.semcdb.2019.03.004. Epub 2019 Apr 9 Review Argemi, J; Ventura-Cots, M; Rachakonda, V; Bataller, R Argemi, Josepmaria; VenturaCots, Meritxell; Rachakonda, Vikrant; Bataller, R. Alcoholic-related liver disease: pathogenesis, management and future therapeutic developments. Rev Esp Enferm Dig. 2020 Nov;112(11):869-878. doi: 10.17235/reed.2020.7242/2020.

Avila, MA; Dufour, JF; Gerbes, AL; Zoulim, F; Bataller, R; Burra, P; Cortez-Pinto, H; Gao, B; Gilmore, I; Mathurin, P; Moreno, C; Poznyak, V; Schnabl, B; Szabo, G; Thiele, M; Thursz, MR. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting. Gut. 2020 Apr;69(4):764780. doi: 10.1136/gutjnl-2019-319720. Epub 2019 Dec 26. Review Canale, M; Casadei-Gardini, A; Ulivi, P; Arechederra, M; Berasain, C; Lollini, PL; Fernandez-Barrena, MG; Avila, MA. Epigenetic Mechanisms in Gastric Cancer: Potential New Therapeutic Opportunities. Int J Mol Sci. 2020 Jul 31;21(15):5500. doi: 10.3390/ijms21155500. Review Claveria-Cabello A, Colyn L, Arechederra M, Urman JM, Berasain C, Avila MA, Fernandez-Barrena MG. Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? Cells 2020 Oct 19;9(10):2321. doi: 10.3390/cells9102321. Article Claveria-Cabello A, Colyn L, Uriarte I, Latasa MU, Arechederra M, Herranz JM, Alvarez L, Urman JM, Martinez-Chantar ML, Banales JM, Sangro B, Rombouts K, Oyarzabal J, Marin JJG, Berasain C, Avila MA, Fernandez-Barrena MG. Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary Inflammation and Fibrosis. Cancers (Basel) 2020 Dec 13;12(12):3748. doi: 10.3390/ cancers12123748. Article Colyn L, Bárcena-Varela M, Álvarez-Sola G, Latasa MU, Uriarte I, Santamaría E, Herranz JM, SantosLaso A, Arechederra M, Ruiz de Gauna M, Aspichueta P, Canale M, Casadei-Gardini A, Francesconi M, Carotti S, Morini S, Nelson LJ, Iraburu MJ, Chen C, Sangro B, Marin JJ, Martinez-Chantar ML, Banales

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Baraibar I, Roman M, Rodríguez-Remírez M, López I, Vilalta A, Guruceaga E, Ecay M, Collantes M, Lozano T, Alignani D, Puyalto A, Oliver A, Ortiz-Espinosa S, Moreno H, Torregrosa M, Rolfo C, Gaglevic C, García-Ros D, Villalba-Esparza M, de Andrea C, Vicent S, Pio R, Lasarte JJ, Calvo A, Ajona D, Gil-Bazo I. Id1 and PD-1 combined blockade impairs tumor growth and survival of KRAS-mutant lung cancer by stimulating PD-L1 expression and tumor infiltrating CD8+ T cells. Cancers (Basel). 2020 Oct 28;12(11):3169. doi: 10.3390/cancers12113169. Article

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Lonial, S; Ghori, RU; Farooqui, MZH; Marinello, P; San-Miguel, J. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. LANCET HAEMATOLOGY. 2019. Valcarcel, LV; Torrano, V; Tobalina, L; Carracedo, A; Planes, FJ. rMTA: robust metabolic transformation analysis. BIOINFORMATICS. 2019. Vicente, C; Arriazu, E; Martinez-Balsalobre, E; Peris, I; Marcotegui, N; Garcia-Ramirez, P; Pippa, R; Rabal, O; Oyarzabal, J; Guruceaga, E; Prosper, F; Mateos, MC; Cayuela, ML; Odero, MD. A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity. CANCER LETTERS. 2019. Walker, BA; Mavrommatis, K; Wardell, CP; Ashby, TC; Bauer, M; Davies, F; Rosenthal, A; Wang, HW; Qu, PP; Hoering, A; Samur, M; Towfic, F; Ortiz, M; Flynt, E; Yu, ZN; Yang, ZH; Rozelle, D; Obenauer, J; Trotter, M; Auclair, D; Keats, J; Bolli, N; Fulciniti, M; Szalat, R; Moreau, P; Durie, B; Stewart, AK; Goldschmidt, H; Raab, MS; Einsele, H; Sonneveld, P; San Miguel, J; Lonial, S; Jackson, GH; Anderson, KC; Avet-Loiseau, H; Munshi, N; Thakurta, A; Morgan, G. A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis. LEUKEMIA. 2019.

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NEUROCIENCIAS Bugallo, R; Marlin, E; Baltanas, A; Toledo, E; Ferrero, R; Vinueza-Gavilanes, R; Larrea, L; Arrasate, M; Aragon, T. Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis. Cell Death Dis. 2020 May 26;11(5):397. doi: 10.1038/s41419020-2601-2. Article Carmona-Abellan, M; Martinez-Valbuena, I; Marcilla, I; DiCaudo, C; Gil, I; Nunez, J; Luquin, MR. Microglia is associated with p-Tau aggregates in the olfactory bulb of patients with neurodegenerative diseases. Neurol Sci. 2021 Apr;42(4):1473-1482. doi: 10.1007/s10072-020-04686-x. Epub 2020 Aug 20. Article; Early Access Dautan, D; Huerta-Ocampo, I; Gut, NK; Valencia, M; Kondabolu, K; Kim, Y; Gerdjikov, TV; Mena-Segovia, J. Cholinergic midbrain afferents modulate striatal circuits and shape encoding of action strategies. Nat Commun. 2020 Apr 8;11(1):1739. doi: 10.1038/ s41467-020-15514-3. di Caudo C, Ivan Martínez-Valbuena , Iñaki-Carril Mundiñano , Aurelie Gennetier , Maria Hernandez , Mar Carmona-Abellan , Irene Marcilla Garcia , Eric J Kremer , Rosario Luquin. CAV-2-Mediated GFP and LRRK2 G2019S Expression in the Macaca fascicularis Brain. Front Mol Neurosci. 2020 Mar 25;13:49. doi: 10.3389/fnmol.2020.00049. eCollection Article Gao, YX; Wang, T; Yu, XH; Zhao, HS; Zeng, P; Ferrari, R; Hernandez, DG; Nails, MA; Rohrers, JD; Ramasamys, A; Kwok, JBJ; Dobson-Stone, C; Brooks, WS; Schofield, PR; Halliday, GM; Hodges, JR; Piguet, O; Bartley, L; Thompson, E; Haan, E; Hernandez, I; Ruiz, A; Boada, M; Borronils, B; Padovani, A; Cruchaga, C;

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Minguez-Olaondo, A; Martinez-Valbuena, I; Romero, S; Fruhbeck, G; Luquin, MR; Martinez-Vila, E; Irimia, P. Excess abdominal fat is associated with cutaneous allodynia in individuals with migraine: a prospective cohort study. J Headache Pain. 2020 Feb 4;21(1):9. doi: 10.1186/s10194-020-1082-0. Article Navalpotro-Gomez, I; Kim, J; Paz-Alonso, PM; Delgado-Alvarado, M; Quiroga-Varela, A; Jimenez-Urbieta, H; Carreiras, M; Strafella, AP; Rodriguez-Oroz, MC. Disrupted salience network dynamics in Parkinson’s disease patients with impulse control disorders. Parkinsonism Relat Disord. 2020 Jan;70:74-81. doi: 10.1016/j.parkreldis.2019.12.009. Epub 2019 Dec 16. Article Pagonabarraga, J; Arbelo, JM; Grandas, F; Luquin, MR; Martin, PM; Rodriguez-Oroz, MC; Valldeoriola, F; Kulisevsky, J. A Spanish Consensus on the Use of Safinamide for Parkinson’s Disease in Clinical Practice. Brain Sci. 2020 Mar 18;10(3):176. doi: 10.3390/brainsci10030176. Review Paz-Alonso, PM; Navalpotro-Gomez, I; Boddy, P; Dacosta-Aguayo, R; Delgado-Alvarado, M; Quiroga-Varela, A; Jimenez-Urbieta, H; Carreiras, M; Rodriguez-Oroz, MC. Functional inhibitory control dynamics in impulse control disorders in Parkinson’s disease. Mov Disord. 2020 Feb;35(2):316-325. doi: 10.1002/mds.27885. Epub 2019 Nov 11. Article Perez-Gonzalez, M; Mendioroz, M; Badesso, S; Sucunza, D; Roldan, M; Espelosin, M; Ursua, S; Lujan, R; Cuadrado-Tejedor, M; Garcia-Osta, A. PLA2G4E, a candidate gene for resilience in Alzheimer’s disease and a new target for dementia treatment. Prog Neurobiol. 2020 Aug;191:101818. doi: 10.1016/j. pneurobio.2020.101818. Epub 2020 May 5. Article Rodriguez-Chinchilla, T; Quiroga-Varela, A; Molinet-Dronda, F; Belloso-Iguerategui, A; Meri-

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Steeds RP. Myocardial fibrosis in asymptomatic and symptomatic severe chronic primary mitral regurgitation and relationship to tissue characterisation and LV function on cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2020 Dec 14;22(1):86. doi: 10.1186/s12968-02000674-4. Article Matilla, L; Roncal, C; Ibarrola, J; Arrieta, V; GarciaPena, A; Fernandez-Celis, A; Navarro, A; Alvarez, V; Gainza, A; Orbe, J; Cachofeiro, V; Zalba, G; Sadaba, R; Rodriguez, JA; Lopez-Andres, N. A Role for MMP-10 (Matrix Metalloproteinase-10) in Calcific Aortic Valve Stenosis. Arterioscler Thromb Vasc Biol. 2020 May;40(5):1370-1382. doi: 10.1161/ ATVBAHA.120.314143. Epub 2020 Mar 19. Article Mora-Gutierrez, JM; Rodriguez, JA; FernandezSeara, MA; Orbe, J; Escalada, FJ; Soler, MJ; Roblero, MFS; Riera, M; Paramo, JA; Garcia-Fernandez, N. MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade. Sci Rep. 2020 Jan 8;10(1):26. doi: 10.1038/s41598019-56856-3. Article Moreno-Ajona, D; Irimia, P; Rodriguez, JA; Garcia-Velloso, MJ; Lopez-Fidalgo, J; FernandezAlonso, L; Grochowitz, L; Munoz, R; Dominguez, P; Gallego-Cullere, J; Martinez-Vila, E. Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study. BMC Cardiovasc Disord. 2020 Feb 26;20(1):93. doi: 10.1186/s12872-020-01387-3. Article Navarro-Oviedo, M; Munoz-Arrondo, R; Zandio, B; Marta-Enguita, J; Bonaterra-Pastra, A; Rodriguez,

JA; Roncal, C; Paramo, JA; Toledo, E; Montaner, J; Hernandez-Guillamon, M; Orbe, J. Circulating TIMP1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage. Sci Rep. 2020 Jun 25;10(1):10329. doi: 10.1038/ s41598-020-67250-9. Article Pei, JY; Harakalova, M; Treibel, TA; Lumbers, RT; Boukens, BJ; Efimov, IR; van Dinter, JT; Gonzalez, A; Lopez, B; El Azzouzi, H; van den Dungen, N; van Dijk, CGM; Krebber, MM; den Ruijter, HM; Pasterkamp, G; Duncker, DJ; Nieuwenhuis, EES; de Weger, R; Huibers, MM; Vink, A; Moore, JH; Moon, JC; Verhaar, MC; Kararigas, G; Mokry, M; Asselbergs, FW; Cheng, C. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts. Clin Epigenetics. 2020 Jul 14;12(1):106. doi: 10.1186/s13148-020-008955. Article Pejenaute, A; Cortes, A; Marques, J; Montero, L; Beloqui, O; Fortuno, A; Marti, A; Orbe, J; Zalba, G. NADPH Oxidase Overactivity Underlies Telomere Shortening in Human Atherosclerosis. Int J Mol Sci. 2020 Feb 20;21(4):1434. doi: 10.3390/ ijms21041434. Article Pellicori P, Ferreira JP, Mariottoni B, Brunner-La Rocca H-P, Ahmed FZ, Job V, Collier T, Cuthbert JJ, Petutschnigg J; Mujaj B, Girerd N, González A, Clark AL, Cosmi F, Staessen JA, Heymans S, Latini R, Rossignol P, Zannad F , Cleland JGF. Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure: rationale, design and baseline characteristics of a proof-of-concept, randomised, precisionmedicine, prevention trial. The « Heart OMics in AGing » (HOMAGE) trial. Eur J Heart Fail. 2020

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Sep;22(9):1711-1723. doi: 10.1002/ejhf.1716. Epub 2020 Jan 16. Article Pichler G, Redon J, Martínez F, Solaz E, Calaforra O, Andrés MS, Lopez B, Díez J, Oberbauer R, Adlbrecht C, Karth GD, Maceira A. Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease. J Hypertens. 2020 Oct;38(10):20362042. doi: 10.1097/HJH.0000000000002504. Article Ravassa S, Beaumont J, Cediel G, Lupón J, López B, Querejeta R, Díez J, Bayés-Genís A, González A. Cardiorenal interaction and heart failure outcomes. A role for IGFBP2? Rev Esp Cardiol (Engl Ed). 2020 Oct;73(10):835-843. doi: 10.1016/j. rec.2019.10.012. Epub 2020 Jan 14. Article Ravassa, S; Gonzalez, A; Bayes-Genis, A; Lupon, J; Diez, J. Myocardial interstitial fibrosis in the era of precision medicine. Biomarker-based phenotyping for a personalized treatment. Rev Esp Cardiol (Engl Ed). 2020 Mar;73(3):248-254. doi: 10.1016/j. rec.2019.09.010. Epub 2019 Nov 20. Article Rincón LM, Sanmartín M, Alonso GL, Rodríguez JA, Muriel A, Casas E, Navarro M, Carbonell A, Lázaro C, Fernández S, González P, Rodríguez M, Jiménez-Mena M, Fernández-Golfín C, Esteban A, García-Bermejo ML, Zamorano JL. A genetic risk score predicts recurrent events after myocardial infarction in young adults. Rev Esp Cardiol (Engl Ed). 2020 Aug;73(8):623-631. doi: 10.1016/j. rec.2019.08.006. Epub 2019 Oct 17. Article Romero-González G, Susana Ravassa, Omar González, Ignacio Lorenzo, Miguel Angel Rojas, Isabel García-Trigo, Nuria García-Fernández,

Javier Lavilla, Paloma L Martín, Begoña López, Arantxa González, Francisco J Beaumont, Gorka San José, María U Moreno, Noelia Ania, Elena Osacar, Pilar Amézqueta, Javier Díez. Burden and challenges of heart failure in patients with chronic kidney disease. A call to action. Nefrologia. May-Jun 2020;40(3):223-236. doi: 10.1016/j. nefro.2019.10.005. Review Saenz-Pipaon, G; San Martin, P; Planell, N; Maillo, A; Ravassa, S; Vilas-Zornoza, A; MartinezAguilar, E; Rodriguez, JA; Alameda, D; LaraAstiaso, D; Prosper, F; Paramo, JA; Orbe, J; Gomez-Cabrero, D; Roncal, C. Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD). J Extracell Vesicles. 2020 Feb 19;9(1):1729646. doi: 10.1080/20013078.2020.1729646. eCollection 2020. Article Schimmel, K; Jung, M; Foinquinos, A; San Jose, G; Beaumont, J; Bock, K; Grote-Levi, L; Xiao, K; Bar, C; Pfanne, A; Just, A; Zimmer, K; Ngoy, S; Lopez, B; Ravassa, S; Samolovac, S; Janssen-Peters, H; Remke, J; Scherf, K; Dangwal, S; Piccoli, MT; Kleemiss, F; Kreutzer, FP; Kenneweg, F; Leonardy, J; Hobuss, L; Santer, L; Do, QT; Geffers, R; Braesen, JH; Schmitz, J; Brandenberger, C; Muller, DN; Wilck, N; Kaever, V; Bahre, H; Batkai, S; Fiedler, J; Alexander, KM; Wertheim, BM; Fisch, S; Liao, R; Diez, J; Gonzalez, A; Thum, T. Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction. Circulation. 2020 Mar 3;141(9):751767. doi: 10.1161/CIRCULATIONAHA.119.042559. Epub 2020 Jan 17. Article

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INMUNOLOGÍA E INMUNOTERAPIA Abengozar-Muela, M; Esparza, MV; Garcia-Ros, D; Vasquez, CE; Echeveste, JI; Idoate, MA; Lozano, MD; Melero, I; de Andrea, CE. Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence. Mod Pathol. 2020 Dec;33(12):25072519. doi: 10.1038/s41379-020-0600-6. Epub 2020 Jun 26. Article Alvarez, M; Dunai, C; Khuat, LT; Aguilar, EG; Barao, I; Murphy, WJ. IL-2 and Anti-TGF-beta Promote NK Cell Reconstitution and Anti-tumor Effects after Syngeneic Hematopoietic Stem Cell Transplantation. Cancers (Basel). 2020 Oct 29;12(11):3189. doi: 10.3390/cancers12113189. Article Alvarez, M; Ochoa, MC; Minute, L; Melero, I; Berraondo, P. Rapid isolation and enrichment of mouse NK cells for experimental purposes. Methods Enzymol. 2020;631:257-275. doi: 10.1016/ bs.mie.2019.10.025. Epub 2019 Nov 20. Review; Book Chapter Alvarez, M; Simonetta, F; Baker, J; Morrison, AR; Wenokur, AS; Pierini, A; Berraondo, P; Negrin, RS. Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion Front Immunol. 2020 Feb 11;11:7. doi: 10.3389/fimmu.2020.00007. eCollection 2020. Article Arasanz, H; Zuazo, M; Bocanegra, A; Gato, M; Martinez-Aguillo, M; Morilla, I; Fernandez, G; Hernandez, B; Lopez, P; Alberdi, N; Hernandez, C; Chocarro, L; Teijeira, L; Vera, R; Kochan, G; Escors, D. Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell

Dynamics. Cancers (Basel). 2020 Feb 4;12(2):344. doi: 10.3390/cancers12020344. Article Arribillaga, L; Echeverria, I; Belsue, V; Gomez, T; Lozano, T; Casares, N; Villanueva, L; Domingos-Pereira, S; Romero, PJ; Nardelli-Haefliger, D; Hervas-Stubbs, S; Sarobe, P; Rodriguez, MJ; Carrascosa, JL; Zurcher, T; Lasarte, JJ. Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens. J Immunother Cancer. 2020 Jun;8(1):e000704. doi: 10.1136/jitc-2020-000704. Article Athie, A; Marchese, FP; Gonzalez, J; Lozano, T; Raimondi, I; Juvvuna, PK; Abad, A; Marin-Bejar, O; Serizay, J; Martinez, D; Ajona, D; Pajares, MJ; Sandoval, J; Montuenga, LM; Kanduri, C; Lasarte, JJ; Huarte, M. Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion. J Cell Biol. 2020 Sep 7;219(9):e201908078. doi: 10.1083/ jcb.201908078. Article Aznar, MA; Molina, C; Teijeira, A; Rodriguez, I; Azpilikueta, A; Garasa, S; Sanchez-Paulete, AR; Cordeiro, L; Etxeberria, I; Alvarez, M; Rius-Rocabert, S; Nistal-Villan, E; Berraondo, P; Melero, I. Repurposing the yellow fever vaccine for intratumoral immunotherapy EMBO EMBO Mol Med. 2020 Jan 9;12(1):e10375. doi: 10.15252/emmm.201910375. Epub 2019 Nov 19. Article Baraibar I, Roman M, Rodríguez-Remírez M, López I, Vilalta A, Guruceaga E, Ecay M, Collantes M, Lozano T, Alignani D, Puyalto A, Oliver A, Ortiz-Espinosa S, Moreno H, Torregrosa M, Rolfo C, Gaglevic C, García-Ros D, Villalba-Esparza M, de Andrea C, Vi-

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cent S, Pio R, Lasarte JJ, Calvo A, Ajona D, Gil-Bazo I. Id1 and PD-1 combined blockade impairs tumor growth and survival of KRAS-mutant lung cancer by stimulating PD-L1 expression and tumor infiltrating CD8+ T cells. Cancers (Basel). 2020 Oct 28;12(11):3169. doi: 10.3390/cancers12113169. Article Cirella A, Berraondo P, Di Trani CA, Melero I. 2020 Dec 1;26(23):6080-6082. Interleukin-12 Message in a Bottle. Clin Cancer Res. 2020 Dec 1;26(23):6080-6082. Comment Eguren-Santamaria, I; Sanmamed, MF; Gil-Bazo, I Are Immune Checkpoint Inhibitors Effective Against Uncommon Oncogene-Driven NSCLC Subtypes?. J Thorac Oncol. 2020 Apr;15(4):489-492. doi: 10.1016/j.jtho.2020.02.003. Editorial Eguren-Santamaria, I; Sanmamed, MF; Goldberg, SB; Kluger, HM; Idoate, MA; Lu, BY; Corral, J; Schalper, KA; Herbst, RS; Gil-Bazo, I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clin Cancer Res. 2020 Aug 15;26(16):4186-4197. doi: 10.1158/10780432.CCR-20-0798. Epub 2020 Apr 30. Review Etxeberria I, Glez-Vaz J, Teijeira Á, Melero I. New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis. ESMO Open 2020 Jul;4(Suppl 3):e000733. Review Etxeberria, I; Olivera, I; Bolanos, E; Cirella, A; Teijeira, A; Berraondo, P; Melero, I. Engineering bionic T cells: signal 1, signal 2, signal 3, reprogramming and the removal of inhibitory mechanisms. Cell Mol Immunol. 2020 Jun;17(6):576-586. doi: 10.1038/ s41423-020-0464-1. Epub 2020 May 20. Review

Fernandez-Sendin, M; Tenesaca, S; Vasquez, M; Aranda, F; Berraondo, P. Production and use of adeno-associated virus vectors as tools for cancer immunotherapy. Methods Enzymol. 2020;635:185203. doi: 10.1016/bs.mie.2019.05.007. Epub 2019 Jun 8.; Book Chapter Fossati, S; Valvi, D; Martinez, D; Cirach, M; Estarlich, M; Fernandez-Somoano, A; Guxens, M; Iniguez, C; Irizar, A; Lertxundi, A; Nieuwenhuijsen, M; Tamayo, I; Vioque, J; Tardon, A; Sunyer, J; Vrijheid, M. Prenatal air pollution exposure and growth and cardio-metabolic risk in pre-schoolers. Environ Int. 2020 May;138:105619. doi: 10.1016/j.envint.2020.105619. Epub 2020 Mar 16. Article Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB, Chan TA, Coukos G, Demaria S, Deutsch E, Draganov D, Edelson RL, Formenti SC, Fucikova J, Gabriele L, Gaipl US, Gameiro SR, Garg AD, Golden E, Han J, Harrington KJ, Hemminki A, Hodge JW, Hossain DMS, Illidge T, Karin M, Kaufman HL, Kepp O, Kroemer G, Lasarte JJ, Loi S, Lotze MT, Manic G, Merghoub T, Melcher AA, Mossman KL, Prosper F, Rekdal Ø, Rescigno M, Riganti C, Sistigu A, Smyth MJ, Spisek R, Stagg J, Strauss BE, Tang D, Tatsuno K, van Gool SW, Vandenabeele P, Yamazaki T, Zamarin D, Zitvogel L, Cesano A, Marincola FM. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020 Mar;8(1):e000337. doi: 10.1136/jitc-2019-000337. Review Gonzalez-Aparicio, M; Alfaro, C. Significance of the IL-8 pathway for immunotherapy. Hum Vaccin Immunother. 2020 Oct 2;16(10):2312-2317. doi: 10.1080/21645515.2019.1696075. Epub 2019 Dec 20. Article

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Ivars, M; Espana, A; Alzuguren, P; Pelacho, B; Lasarte, JJ; Lopez-Zabalza, MJ. The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient. Br J Dermatol. 2020 May;182(5):1194-1204. doi: 10.1111/bjd.18382. Epub 2019 Oct 15. Article Lopez-Janeiro, A; Padilla-Ansala, C; de Andrea, CE; Hardisson, D; Melero, I. Prognostic value of macrophage polarization markers in epithelial neoplasms and melanoma. A systematic review and meta-analysis. Mod Pathol. 2020 Aug;33(8):1458-1465. doi: 10.1038/s41379-020-0534-z. Epub 2020 Apr 14. Review Márquez-Rodas I, Longo F, Rodriguez-Ruiz ME, Calles A, Ponce S, Jove M, Rubio-Viqueira B, Perez-Gracia JL, Gómez-Rueda A, López-Tarruella S, Ponz-Sarvise M, Álvarez R, Soria-Rivas A, de Miguel E, Ramos-Medina R, Castañon E, Gajate P, Sempere-Ortega C, Jiménez-Aguilar E, Aznar MA, Calvo A, Lopez-Casas PP, Martín-Algarra S, Martín M, Tersago D, Quintero M, Melero I. Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors. Sci Transl Med. 2020 Oct 14;12(565):eabb0391. doi: 10.1126/scitranslmed. abb0391. Article Mastelic-Gavillet, B; Sarivalasis, A; Lozano, LE; Wyss, T; Inoges, S; de Vries, IJM; Dartiguenave, F; Jichlinski, P; Derre, L; Coukos, G; Melero, I; Harari, A; Romero, P; Vigano, S; Kandalaft, LE. Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer. Eur J Cancer. 2020 Aug;135:173-182. doi: 10.1016/j. ejca.2020.04.036. Epub 2020 Jun 23. Article

Melero I, Berraondo P. 4-1BB (CD137) in anticancer chimeras. J Exp Med. 2020 Dec 7;217(12):e20201562. doi: 10.1084/jem.20201562. Comment Melero I, Gato M 2, Tala Shekarian 3, Angela Aznar 2, Sandrine Valsesia-Wittmann 3, Christophe Caux 3, Iñaki Etxeberrria 2, Alvaro Teijeira 2, Aurelien Marabelle 4. Repurposing infectious disease vaccines for intratumoral immunotherapy. J Immunother Cancer. 2020 Feb;8(1):e000443. doi: 10.1136/ jitc-2019-000443. Article Melero, I; Alvarez, M; Minute, L; Berraondo, P Premortem Tumor Stress in Radioimmunotherapy. Trends Cancer. 2020 Mar;6(3):173-174. doi: 10.1016/j.trecan.2020.01.001. Epub 2020 Jan 27. Article Mielgo-Rubio X, Calvo V, Luna J, Remon J, Martín M, Berraondo P, Jarabo JR, Higuera O, Conde E, De Castro J, Provencio M, Hernando Trancho F, LópezRíos F, Couñago F. 2020 Nov 20;12(11):3459. Immunotherapy Moves to the Early-Stage Setting in Non-Small Cell Lung Cancer: Emerging Evidence and the Role of Biomarkers. Cancers (Basel). 2020 Nov 20;12(11):3459. doi: 10.3390/cancers12113459. Review Minute, L; Teijeira, A; Sanchez-Paulete, AR; Ochoa, MC; Alvarez, M; Otano, I; Etxeberrria, I; Bolanos, E; Azpilikueta, A; Garasa, S; Casares, N; Gracia, JLP; Rodriguez-Ruiz, ME; Berraondo, P; Melero, I. Cellular cytotoxicity is a form of immunogenic cell death. J Immunother Cancer. 2020 Mar;8(1):e000325. doi: 10.1136/jitc-2019-000325. Article Olivera, I; Etxeberria, I; Bolanos, E; Gato-Canas, M; Melero, I. Exploiting TCR Recognition of Shared

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Hotspot Oncogene-encoded Neoantigens. Clin Cancer Res. 2020 Mar 15;26(6):1203-1204. doi: 10.1158/1078-0432.CCR-19-3813. Epub 2020 Jan 30. Comment Otano, I; Alvarez, M; Minute, L; Ochoa, MC; Migueliz, I; Molina, C; Azpilikueta, A; de Andrea, CE; Etxeberria, I; Sanmamed, MF; Teijeira, A; Berraondo, P; Melero, I. Human CD8 T cells are susceptible to TNF-mediated activation-induced cell death. Theranostics. 2020 Mar 15;10(10):4481-4489. doi: 10.7150/thno.41646. eCollection 2020. Article Pérez-Ruiz E, Melero I, Kopecka J, Sarmento-Ribeiro AB, García-Aranda M, De Las Rivas J. Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies. Drug Resist Updat. 2020 Dec;53:100718. doi: 10.1016/j.drup.2020.100718. Epub 2020 Jul 15. Review Rodriguez-Ruiz, ME; Vitale, I; Harrington, KJ; Melero, I; Galluzzi, L. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat Immunol. 2020 Feb;21(2):120-134. doi: 10.1038/s41590-019-0561-4. Epub 2019 Dec 23. Review Rodriguez-Ruiz, ME; Yamazaki, T; Buque, A; Bloy, N; Silva, VAO; Stafford, L; Sato, A; Galluzzi, L. Monitoring abscopal responses to radiation in mice. Methods Enzymol. 2020;635:111-125. doi: 10.1016/ bs.mie.2019.04.014. Epub 2019 Apr 15. Book Chapter Sanmamed, MF; Eguren-Santamaria, I; Schalper, KA Overview of Lung Cancer Immunotherapy. Cancer J. Nov/Dec 2020;26(6):473-484. doi: 10.1097/ PPO.0000000000000488. Review

Schalper, KA; Carleton, M; Zhou, M; Chen, T; Feng, Y; Huang, SP; Walsh, AM; Baxi, V; Pandya, D; Baradet, T; Locke, D; Wu, QY; Reilly, TP; Phillips, P; Nagineni, V; Gianino, N; Gu, JL; Zhao, HY; Perez-Gracia, JL; Sanmamed, MF; Melero, I. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors. Nat Med. 2020 May;26(5):688-692. doi: 10.1038/s41591-0200856-x. Epub 2020 May 11. Article Silva L, Egea J, Villanueva L, Ruiz M, Llopiz D, Repáraz D, Aparicio B, Lasarte-Cia A, Lasarte JJ, Ruiz de Galarreta M, Lujambio A, Sangro B, Sarobe P. Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses Against Hepatocellular Carcinoma. Cancers (Basel). 2020 Nov 16;12(11):3397. doi: 10.3390/cancers12113397. Article Silva-Pilipich N, Martisova E, Ballesteros-Briones MC, Hervas-Stubbs S, Casares N, González-Sapienza G, Smerdou C, Vanrell L. Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity. Biomedicines. 2020 Dec 2;8(12):562. doi: 10.3390/biomedicines8120562. Article Teijeira A, Garasa S, Ochoa MC, Villalba Esparza M, Olivera I, Cirella A, Eguren-Santamaria I, Berraondo P, Schalper KA, de Andrea CE, Sanmamed MF, Melero I. 2020 Dec 29:clincanres.. Interleukin-8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy. Clin Cancer Res. 2020 Dec 29. doi: 10.1158/1078-0432.CCR20-1319. Online ahead of print. Review Teijeira, A; Garasa, S; Gato, M; Alfaro, C; Migueliz, I; Cirella, A; de Andrea, C; Ochoa, MC; Otano, I;

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Etxeberria, I; Andueza, MP; Nieto, CP; Resano, L; Azpilikueta, A; Allegretti, M; de Pizzol, M; Ponz-Sarvise, M; Rouzaut, A; Sanmamed, MF; Schalper, K; Carleton, M; Mellado, M; Rodriguez-Ruiz, ME; Berraondo, P; Perez-Gracia, JL; Melero, I. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. Immunity. 2020 May 19;52(5):856-871.e8. doi: 10.1016/j.immuni.2020.03.001. Epub 2020 Apr 13. Article Tenesaca, S; Vasquez, M; Fernandez-Sendin, M; Di Trani, CA; Ardaiz, N; Gomar, C; Cuculescu, D; Alvarez, M; Otano, I; Melero, I; Berraondo, P. Scavenger Receptor Class B Type I is Required for 25-Hydroxycholecalciferol Cellular Uptake and Signaling in Myeloid Cells. Mol Nutr Food Res. 2020 Aug;64(15):e1901213. doi: 10.1002/ mnfr.201901213. Epub 2020 Jul 8. Article Velasco-de Andres, M; Casado-Llombart, S; Catala, C; Leyton-Pereira, A; Lozano, F; Aranda, F. Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents. Cells. 2020 Dec 3;9(12):2589. doi: 10.3390/cells9122589. Review Vrijheid, M; Fossati, S; Maitre, L; Marquez, S; Roumeliotaki, T; Agier, L; Andrusaityte, S; Cadiou, S; Casas, M; de Castro, M; Dedele, A; Donaire-Gonzalez, D; Grazuleviciene, R; Haug, LS; McEachan, R; Meltzer, HM; Papadopouplou, E; Robinson, O; Sakhi, AK; Siroux, V; Sunyer, J; Schwarze, PE; Tamayo-Uria, I; Urquiza, J; Vafeiadi, M; Valentin, A; Warembourg, C; Wright, J; Nieuwenhuijsen, MJ; Thomsen, C; Basagana, X; Slama, R; Chatzi, L. Early -Life Environmental Exposures and Childhood Obesity: An Exposome-Wide Approach. Environ Health

Perspect. 2020 Jun;128(6):67009. doi: 10.1289/ EHP5975. Epub 2020 Jun 24. Article Wculek, SK; Cueto, FJ; Mujal, AM; Melero, I; Krummel, MF; Sancho, D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020 Jan;20(1):7-24. doi: 10.1038/s41577-0190210-z. Epub 2019 Aug 29. Review Wischhusen, J; Melero, I; Fridman, WH Growth/ Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020 May 19;11:951. doi: 10.3389/fimmu.2020.00951. eCollection 2020. Review Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, Melero I, Kudo M, Hou MM, Matilla A, Tovoli F, Knox JJ, Ruth He A, El-Rayes BF, Acosta-Rivera M, Lim HY, Neely J, Shen Y, Wisniewski T, Anderson J, Hsu C. . 2020 Oct 1;6(11):e204564. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(11):e204564. doi: 10.1001/jamaoncol.2020.4564. Online ahead of print. Article

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TERAPIA GÉNICA Y REGULACIÓN DE LA EXPRESIÓN GÉNICA Anasagasti A, Lara-López A, Milla-Navarro S, Escudero-Arrarás L, Rodríguez-Hidalgo M, Zabaleta N, González Aseguinolaza G, de la Villa P, Ruiz-Ederra J. Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa. Pharmaceutics 2020 Sep 24;12(10):913. doi: 10.3390/ pharmaceutics12100913. Arcas, A; Wilkinson, DG; Nieto, MA. The Evolutionary History of Ephs and Ephrins: Toward Multicellular Organisms. Mol Biol Evol 2020 Feb 1;37(2):379394. Armengaud, J; Delaunay-Moisan, A; Thuret, JY; van Anken, E; Acosta-Alvear, D; Aragón, T; Arias, C; Blondel, M; Braakman, I; Collet, JF; Courcol, R; Danchin, A; Deleuze, JF; Lavigne, JP; Lucas, S; Michiels, T; Moore, ERB; Nixon-Abell, J; RosselloMora, R; Shi, ZL; Siccardi, AG; Sitia, R; Tillett, D; Timmis, KN; Toledano, MB; van der Sluijs, P; Vicenzi, E. The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19. Environ Microbiol 2020 Jun;22(6):1997-2000. Editorial Material Athie, A; Marchese, FP; Gonzalez, J; Lozano, T; Raimondi, I; Juvvuna, PK; Abad, A; Marin-Bejar, O; Serizay, J; Martinez, D; Ajona, D; Pajares, MJ; Sandoval, J; Montuenga, LM; Kanduri, C; Lasarte, JJ; Huarte, M. Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion. J Cell Biol. 2020 Sep 7;219(9):e201908078. doi: 10.1083/ jcb.201908078.

Ballesteros-Briones MC, Noelia Silva-Pilipich, Guillermo Herrador-Cañete, Lucia Vanrell, Cristian Smerdou. A new generation of vaccines based on alphavirus self-amplifying RNA. Curr Opin Virol. 2020 Oct;44:145-153. Review Biswas M, Marsic D, Li N, Zou C, GonzalezAseguinolaza G, Zolotukhin I, Kumar SRP, Rana J, Butterfield JSS, Kondratov O, de Jong YP, Herzog RW, Zolotukhin S. Engineering and In Vitro Selection of a Novel AAV3B Variant with High Hepatocyte Tropism and Reduced Seroreactivity. Mol Ther Methods Clin Dev 2020 Oct 4;19:347-361. Bugallo, R; Marlin, E; Baltanas, A; Toledo, E; Ferrero, R; Vinueza-Gavilanes, R; Larrea, L; Arrasate, M; Aragon, T. Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis. Cell Death Dis 2020 May 26;11(5):397. doi: 10.1038/s41419020-2601-2. Castroviejo, N; Ocaña, OH; Rago, L; Coskun, H; Arcas, A; Galceran, J; Nieto, MA. Reply to: Zebrafish prrx1a mutants have normal hearts. Nature 2020 Sep;585(7826):E17-E19. Editorial Material Diaz-Perdigon, T; Belloch, FB; Ricobaraza, A; Elboray, EE; Suzuki, T; Tordera, RM; Puerta, E. Early sirtuin 2 inhibition prevents age-related cognitive decline in a senescence-accelerated mouse model. Neuropsychopharmacology 2020 Jan;45(2):347357. Fresquet V, Garcia-Barchino MJ, Larrayoz M, Celay J, Vicente C, Fernandez-Galilea M, Larrayoz MJ, Calasanz MJ, Panizo C, Junza A, Han J, Prior C, Fortes P, Pio R, Oyarzabal J, Martinez-Baztan A, Paiva B, Moreno-Aliaga MJ, Odero MD, Agirre

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X, Yanes O, Prosper F, Martinez-Climent JA. Endogenous retroelement activation by epigenetic therapy reverses the Warburg effect and elicits mitochondrial-mediated cancer cell death. Cancer Discovery 2020 Dec 18;CD-20-1065. doi: 10.1158/2159-8290.CD-20-1065. Garcia-Olloqui, P; Rodriguez-Madoz, JR; Di Scala, M; Abizanda, G; Vales, A; Olague, C; Iglesias-Garcia, O; Larequi, E; Aguado-Alvaro, LP; Ruiz-Villalba, A; Prosper, F; Gonzalez-Aseguinolaza, G; Pelacho, B. Effect of heart ischemia and administration route on biodistribution and transduction efficiency of AAV9 vectors. J Tissue Eng Regen Med 2020 Jan;14(1):123-134. Gonzalez-Aparicio, M; Alfaro, C. Significance of the IL-8 pathway for immunotherapy. Hum Vaccin Immunother. 2020 Oct 2;16(10):2312-2317. Review Gonzalez-Aseguinolaza, G. Givosiran - Running RNA Interference to Fight Porphyria Attacks. N Engl J Med. 2020 Jun 11;382(24):2366-2367. Editorial Material Grossi, E; Raimondi, I; Goni, E; Gonzalez, J; Marchese, FP; Chapaprieta, V; Martin-Subero, JI; Guo, SL; Huarte, M. A IncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions. Nat Commun 2020 Feb 18;11(1):936. doi: 10.1038/s41467-020-14623-3. Jericó D, Luis EO, Cussó L, Fernández-Seara MA, Morales X, Córdoba KM, Benito M, Sampedro A, Larriva M, Ramírez MJ, de Salamanca RE, Ortiz-deSolorzano C, Alegre M, Prieto J, Lanciego JL, D’Avola D, González-Aseguinolaza G, Pastor MA, Desco M, Fontanellas A. Brain ventricular enlargement in

human and murine acute intermittent porphyria. Hum Mol Genet 2020 Nov 25;29(19):3211-3223. Lasa M, Neri L, Carte B, Gázquez C, Aragón T, Aldabe R. Maturation of NAA20 Aminoterminal End Is Essential to Assemble NatB N-Terminal Acetyltransferase Complex. J Mol Biol. 2020 Nov 6;432(22):5889-5901. López-Manzaneda S, Ojeda-Pérez I, Zabaleta N, García-Torralba A, Alberquilla O, Torres R, SánchezDomínguez R, Torella L, Olivier E, Mountford J, Ramírez JC, Bueren JA, González-Aseguinolaza G, Segovia JC. In Vitro and In Vivo Genetic Disease Modeling via NHEJ-Precise Deletions Using CRISPR-Cas9. Mol Ther Methods Clin Dev 2020 Oct 15;19:426-437. Martin-Suarez, S; Abiega, O; Ricobaraza, A; Hernandez-Alcoceba, R; Encinas, JM. Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome. Front Cell Dev Biol 2020 Jul 21;8:654. doi: 10.3389/fcell.2020.00654. eCollection 2020. Mas, AM; Huarte, M. lncRNA-DNA hybrids regulate distant genes. EMBO Rep. 2020 Mar 4;21(3):e50107. doi: 10.15252/embr.202050107. Editorial Material Ricobaraza, A; Gonzalez-Aparicio, M; MoraJimenez, L; Lumbreras, S; Hernandez-Alcoceba, R. High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy. Int J Mol Sci. 2020 May 21;21(10):3643. doi: 10.3390/ijms21103643. Review Santos-Laso, A; Izquierdo-Sanchez, L; Rodrigues, PM; Huang, BQ; Azkargorta, M; Lapitz, A; Munoz-

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Garrido, P; Arbelaiz, A; Caballero-Camino, FJ; Fernandez-Barrena, MG; Jimenez-Aguero, R; Argemi, J; Aragon, T; Elortza, F; Marzioni, M; Drenth, JPH; LaRusso, NF; Bujanda, L; Perugorria, MJ; Banales, JM. Proteostasis disturbances and endoplasmic reticulum stress contribute to polycystic liver disease: New therapeutic targets. Liver Int. 2020 Jul;40(7):1670-1685. Silva-Pilipich N, Martisova E, Ballesteros-Briones MC, Hervas-Stubbs S, Casares N, GonzálezSapienza G, Smerdou C, Vanrell L. Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity. Biomedicines. 2020 Dec 2;8(12):562. doi: 10.3390/biomedicines8120562. Simões IT, Aranda F, Casadó-Llombart S, Velascode Andrés M, Català C, Álvarez P, ConsuegraFernández M, Orta-Mascaró M, Merino R, Merino J, Alberola-Ila J, González-Aseguinolaza G, Carreras E, Martínez V, Lozano F. Multifaceted effects of soluble human CD6 in experimental cancer models. Journal for ImmunoTherapy of Cancer. J Immunother Cancer. 2020 Mar;8(1):e000172. doi: 10.1136/jitc-2019-000172. Suarez, B; Prats-Mari, L; Unfried, JP; Fortes, P. LncRNAs in the Type I Interferon Antiviral Response. Int J Mol Sci 2020 Sep 3;21(17):6447. doi: 10.3390/ijms21176447. Review Unfried, JP; Fortes, P. LncRNAs in HCV Infection and HCV-Related Liver Disease. Int J Mol Sci. 2020 Mar 24;21(6):2255. doi: 10.3390/ijms21062255. Review

Unfried, JP; Fortes, P. SMIM30, a tiny protein with a big role in liver cancer. J Hepatol. 2020 Nov;73(5):1010-1012. Valencia, K; Erice, O; Kostyrko, K; Hausmann, S; Guruceaga, E; Tathireddy, A; Flores, NM; Sayles, LC; Lee, AG; Fragoso, R; Sun, TQ; Vallejo, A; Roman, M; Entrialgo-Cadierno, R; Migueliz, I; Razquin, N; Fortes, P; Lecanda, F; Lu, J; Ponz-Sarvise, M; Chen, CZ; Mazur, PK; Sweet-Cordero, EA; Vicent, S. The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas. J Clin Invest 2020 Apr 1;130(4):1879-1895. Vinueza-Gavilanes, R; Inigo-Marco, I; Larrea, L; Lasa, M; Carte, B; Santamaria, E; Fernandez-Irigoyen, J; Bugallo, R; Aragon, T; Aldabe, R; Arrasate, M. N-terminal acetylation mutants affect alphasynuclein stability, protein levels and neuronal toxicity. Neurobiol Dis. 2020 Apr;137:104781. doi: 10.1016/j.nbd.2020.104781. Zalba, S; Contreras-Sandoval, AM; Martisova, E; Debets, R; Smerdou, C; Garrido, MJ. Quantification of Pharmacokinetic Profiles of PD-1/PD-L1 Antibodies by Validated ELISAs. Pharmaceutics 2020 Jun 26;12(6):595.

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MEDICINA REGENERATIVA Garcia-Olloqui, P; Rodriguez-Madoz, JR; Di Scala, M; Abizanda, G; Vales, A; Olague, C; Iglesias-Garcia, O; Larequi, E; Aguado-Alvaro, LP; Ruiz-Villalba, A; Prosper, F; Gonzalez-Aseguinolaza, G; Pelacho, B. Effect of heart ischemia and administration route on biodistribution and transduction efficiency of AAV9 vectors. J Tissue Eng Regen Med 2020 Jan;14(1):123-134. Ivars, M; Espana, A; Alzuguren, P; Pelacho, B; Lasarte, JJ; Lopez-Zabalza, MJ. The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient. Br J Dermatol 2020 May;182(5):1194-1204. Lamo-Espinosa JM, Blanco JF, Sánchez M, Moreno V, Granero-Moltó F, Sánchez-Guijo F, Crespo-Cullel Í, Mora G, San Vicente DD, Pompei-Fernández O, Aquerreta JD, Núñez-Córdoba JM, Vitoria Sola M, Valentí-Azcárate A, Andreu EJ, Del Consuelo Del Cañizo M, Valentí-Nin JR, Prósper F. Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis. J Transl Med 2020 Sep 18;18(1):356. López-Muneta L, Miranda-Arrubla J, Carvajal-Vergara X. The Future of Direct Cardiac Reprogramming: Any GMT Cocktail Variety? Int J Mol Sci 2020 Oct 26;21(21):7950. doi: 10.3390/ijms21217950. Montero, P; Flandes-Iparraguirre, M; Musquiz, S; Araluce, MP; Plano, D; Sanmartin, C; Orive, G; Gavira, JJ; Prosper, F; Mazo, MM. Cells, Materials, and Fabrication Processes for Cardiac Tissue Engineer-

ing. Front Bioeng Biotechnol 2020 Aug 11;8:955. doi: 10.3389/fbioe.2020.00955. eCollection 2020. Review Nandi, R; Yucknovsky, A; Mazo, MM; Amdursky, N. Exploring the inner environment of protein hydrogels with fluorescence spectroscopy towards understanding their drug delivery capabilities. J Mater Chem B 2020 Aug 12;8(31):6964-6974. Rivaud, MR; Marchal, GA; Wolswinkel, R; Jansen, JA; van der Made, I; Beekman, L; Ruiz-Villalba, A; Baartscheer, A; Rajamani, S; Belardinelli, L; van Veen, TAB; Basso, C; Thiene, G; Creemers, EE; Bezzina, CR; Remme, CA Rivaud, Mathilde R.; Marchal, Gerard A.; Wolswinkel, Rianne; Jansen, John A.; van der Made, Ingeborg; Beekman, Leander; Ruiz-Villalba, Adrian; Baartscheer, Antonius; Rajamani, Sridharan; Belardinelli, Luiz; van Veen, Toon A. B.; Basso, Cristina; Thiene, Gaetano; Creemers, Esther E.; Bezzina, Connie R.; Remme, Carol Ann. Functional modulation of atrio-ventricular conduction by enhanced late sodium current and calcium-dependent mechanisms in Scn5a(1798insDl+) mice. Europace. 2020 Oct 1;22(10):1579-1589. Ruiz-Villalba A, Romero JP, Hernández SC, Vilas-Zornoza A, Fortelny N, Castro-Labrador L, San Martin-Uriz P, Lorenzo-Vivas E, García-Olloqui P, Palacio M, Gavira JJ, Bastarrika G, Janssens S, Wu M, Iglesias E, Abizanda G, de Morentin XM, Lasaga M, Planell N, Bock C, Alignani D, Medal G, Prudovsky I, Jin YR, Ryzhov S, Yin H, Pelacho B, Gomez-Cabrero D, Lindner V, Lara-Astiaso D, Prósper F. Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction. Circulation. 2020 Nov 10;142(19):1831-1847.

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Sanchez-Guijo, F; Garcia-Olmo, D; Prosper, F; Martinez, S; Zapata, A; Fernandez-Aviles, F; Toledo-Aral, JJ; Torres, M; Farinas, I; Badimon, L; Labandeira-Garcia, JL; Garcia-Sancho, J; Moraleda, JM. Spanish Cell Therapy Network (TerCel): 15 years of successful collaborative translational research. Cytotherapy 2020 Jan;22(1):1-5. Review Sanchez-Herrero A, Calvo IA, Flandes-Iparraguirre M, Landgraf M, Lahr CA, Shafiee A, Granero-Molto F, Saez B, Mazo MM, Paiva B, de Juan Pardo E, Nicol A, Prosper F, Bray LJ, McGovern JA. Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer. Cancers (Basel) 2020 Aug 6;12(8):2205. doi: 10.3390/cancers12082205. TERAPIAS MOLECULARES Fresquet V, Garcia-Barchino MJ, Larrayoz M, Celay J, Vicente C, Fernandez-Galilea M, Larrayoz MJ, Calasanz MJ, Panizo C, Junza A, Han J, Prior C, Fortes P, Pio R, Oyarzabal J, Martinez-Baztan A, Paiva B, Moreno-Aliaga MJ, Odero MD, Agirre X, Yanes O, Prosper F, Martinez-Climent JA. Endogenous retroelement activation by epigenetic therapy reverses the Warburg effect and elicits mitochondrial-mediated cancer cell death. Cancer Discovery 2020 Dec 18;CD-20-1065. doi: 10.1158/2159-8290.CD20-1065. Garbayo, E; Pascual-Gil, S; Rodriguez-Nogales, C; Saludas, L; de Mendoza, AEH; Blanco-Prieto, MJ. Nanomedicine and drug delivery systems in cancer and regenerative medicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020 Sep;12(5):e1637. Review

Vicente, C; Arriazu, E; Martinez-Balsalobre, E; Peris, I; Marcotegui, N; Garcia-Ramirez, P; Pippa, R; Rabal, O; Oyarzabal, J; Guruceaga, E; Prosper, F; Mateos, MC; Cayuela, ML; Odero, MD. A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity. Cancer Lett. 2020 Jan 1;468:1-13. Sola, M; Menon, AP; Moreno, B; Meraviglia-Crivelli, D; Soldevilla, MM; Carton-Garcia, F; Pastor, F. Aptamers Against Live Targets: Is In Vivo SELEX Finally Coming to the Edge?. Mol Ther Nucleic Acids 2020 Sep 4;21:192-204. Review Codony, S; Pujol, E; Pizarro, J; Feixas, F; Valverde, E; Loza, MI; Brea, JM; Saez, E; Oyarzabal, J; Pineda-Lucena, A; Perez, B; Perez, C; Rodriguez-Franco, MI; Leiva, R; Osuna, S; Morisseau, C; Hammock, BD; Vaquez-Carrera, M; Vazquez, S. 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors: In Vivo Evaluation in a Murine Model of Acute Pancreatitis. J Med Chem 2020 Sep 10;63(17):9237-9257. Pereira-Caro, G; Clifford, MN; Polyviou, T; Ludwig, IA; Alfheeaid, H; Moreno-Rojas, JM; Garcia, AL; Malkova, D; Crozier, A. Plasma pharmacokinetics of (poly)phenol metabolites and catabolites after ingestion of orange juice by endurance trained men. Free Radic Biol Med 2020 Nov 20;160:784-795. Claveria-Cabello, A; Colyn, L; Uriarte, I; Latasa, MU; Arechederra, M; Herranz, JM; Alvarez, L; Urman, JM; Martinez-Chantar, ML; Banales, JM; Sangro, B; Rombouts, K; Oyarzabal, J; Marin, JJG; Berasain, C; Avila, MA; Fernandez-Barrena, MG. Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary In-

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flammation and Fibrosis. Cancers (Basel) 2020 Dec 13;12(12):3748. doi: 10.3390/cancers12123748. Urman, JM; Herranz, JM; Uriarte, I; Rullan, M; Oyon, D; Gonzalez, B; Fernandez-Urien, I; Carrascosa, J; Bolado, F; Zabalza, L; Arechederra, M; Alvarez-Sola, G; Colyn, L; Latasa, MU; Puchades-Carrasco, L; Pineda-Lucena, A; Iraburu, MJ; Iruarrizaga-Lejarreta, M; Alonso, C; Sangro, B; Purroy, A; Gil, I; Carmona, L; Cubero, FJ; Martinez-Chantar, ML; Banales, JM; Romero, MR; Macias, RIR; Monte, MJ; Marin, JJG; Vila, JJ; Corrales, FJ; Berasain, C; Fernandez-Barrena, MG; Avila, MA. Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach. Cancers (Basel) 2020 Jun 21;12(6):1644. doi: 10.3390/cancers12061644. Albors-Vaquer A, Rizvi A, Matzapetakis M, Lamosa P, Coelho AV, Patel AB, Mande SC, Gaddam S, Pineda-Lucena A, Banerjee S, Puchades-Carrasco L. Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers. Emerg Microbes Infect 2020 Dec;9(1):1131-1139. Yuste, S; Macia, A; Motilva, MJ; Prieto-Diez, N; Romero, MP; Pedret, A; Sola, R; Ludwig, IA; Rubio, L. Yuste, Silvia; Macia, Alba; Motilva, Maria-Jose; Prieto-Diez, Neus; Romero, Maria-Paz; Pedret, Anna; Sola, Rosa; Ludwig, Iziar A.; Rubio, L. Thermal and non-thermal processing of red-fleshed apple: how are (poly)phenol composition and bioavailability affected?. Food Funct 2020 Dec 1;11(12):1043610447.

Gomez-Cebrian, N; Garcia-Flores, M; Rubio-Briones, J; Lopez-Guerrero, JA; Pineda-Lucena, A; Puchades-Carrasco, L. Targeted Metabolomics Analyses Reveal Specific Metabolic Alterations in High-Grade Prostate Cancer Patients. J Proteome Res 2020 Oct 2;19(10):4082-4092. Vicente-Munoz, S; Cobo, T; Puchades-Carrasco, L; Sanchez-Garcia, AB; Agust, N; Palacio, M; Pineda-Lucena, A; Gratacos, E. Vaginal metabolome: towards a minimally invasive diagnosis of microbial invasion of the amniotic cavity in women with preterm labor. Sci Rep 2020 Mar 25;10(1):5465. doi: 10.1038/s41598-020-62542-6.

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2.3. Proyectos competitivos

PROYECTOS

Durante el curso 2020-2021 se han obtenido 63 proyectos en convocatorias nacionales e internacionales, públicas y privadas.

6.700.000 €

IMPORTE TOTAL DE CONCESIONES NACIONALES E INTERNACIONALES

PROYECTO INTERNACIONALES ACRÓNIMO

TÍTULO

INVESTIGADOR CONVOCATORIA

DESTINATION

AI-enabled RNA nanotechnology DElivery SysTem for INformATION transfer into cells. Medicina de precisión en las enfermedades hepatobiliares: el valor de un “bilebank” regional Advanced bioengineering of an allhuman platform to study transthyretin amyloid cardiomyopathy

Fernando Pastor

H2020-FETOPEN-2020 509.183,75 €

19/01/2021

Carmen Berasain

15/01/2021

Red de Excelencia para el desarrollo de Terapias Avanzadas de tratamiento del Infarto de Miocardio basadas en medicina regenerativa e impresión 3D Tratamiento personalizado en radioterapia mediante modelado integrado de nuevas restricciones y efectos dosimétricos locales

Beatríz Pelacho

Eurorregión Nueva 75.000€ Aquitania-EuskadiNavarra 2020 Pfizer Global $149,907.66 medical Grants: Junior Investigator Transthyretin Amyloid Cardiomyopathy (ATTRCM) Research Interreg Sudoe SOE4/ 123.750€ P1/E1063

EraPerMed 2020

24/11/2020

BILEBANK

CARDIOPATCH

PerPlanRT

Olalla Iglesias

Felipe Calvo

FINANCIACIÓN

108.150€

CONCESIÓN

02/07/2021

21/10/2020

Cima Universidad de Navarra 62

PROYECTO NACIONALES

FINANCIADOR

INVESTIGADOR PRINCIPAL

TÍTULO COMPLETO

Asociación Española Contra el Cáncer (Lab AECC 2020)

GARCÍA FERNÁNDEZ DE BARRENA, MAITE

New Epigenetic Approaches For The Treatment of Liver and Digestive Tumors

Asociación Española Contra el Cáncer (Estrategicos AECC 2020)

LECANDA CORDERO, FERNANDO

Combinatorial Immunotherapies in a novel GEMM platform for sarcomas: Identification of Therapeutic Efficacy and anticipating Adverse Events

Asociación Española Contra el Cáncer (AECC Cáncer Innova 2020) SAN JOSÉ ENÉRIZ, EDURNE

Towards a new paradigm in the treatment of bladder carcinoma: the combination of an epigenetic agent and an immune checkpoint inhibitor

Asociación Española Contra el Cáncer (Estrategicos AECC 2020)

VICENT CAMBRA, SILVESTRE

Rational gene signature-based drug combinations for lung cancer treatment

Astra Zeneca Farmaceutica Spain

PARDO SAGANTA, ANA

Los mecanismos fisiopatológicos implicados en el desarrollo de enfermedades respiratorias y la regeneración del tejido pulmonar dañado

Dravet Syndrome Foundation

HERNÁNDEZ ALCOCEBA, RUBËN

Reduction of inflammatory responses against adenoviral vectors to improve safety and efficacy of gene therapy for Dravet syndrome (RIRADS)

Fundación Bancaria La Caixa (CAIXAIMPULSE Validate)

FORTES ALONSO, MARIA PURIFICACION

Riboswitches On U1 snRNP for Therapeutic Expression Regulation

Fundación Bancaria La Caixa (CAIXAIMPULSE Validate)

GARCÍA OSTA, ANA MARÍA

PLA2G4E: a new target for dementia treatment

Fundación Bancaria La Caixa (Health Research)

HUARTE MARTÍNEZ, MAITE

lncRNAs-RS-CRC. Understanding lncRNAs in replicative stress and colorectal cancer: from cancer biology to single-molecules

Fundación Bancaria La Caixa (Health Research)

MELERO BERMEJO, IGNACIO JAVIER

ACTILNET. INTERLEUKIN-8 AND NEUTROPHIL EXTRACELULAR TRAPS AS ACTIONABLE HURDLES FOR CANCER IMMUNOTHERAPY

Fundación Bancaria La Caixa (Convenio)

HERNÁNDEZ ALCOCEBA, RUBÉN

Optimización del protocolo de producción de vectores adenovirales de alta capacidad y aplicación a vectores específicos para el síndrome de Dravet (VEASID).

Fundación Bancaria La Caixa (Convenio)

VALENCIA LEOZ, KARMELE

Identificación de inhibidores de DSTYK con actividad antitumoral (DSTYK-INH)

Fundación Bancaria La Caixa (Convenio)

PÉREZ RUIZ, ANA ISABEL

Tratamiento anti-adipogénico en lesiones tendinomusculares (ANTIADIPOTEN)

Fundación Olga Torres

TEIJEIRA SÁNCHEZ, ALVARO

Spatiotemporal dynamics of antitumor and pro-tumor immune responses in nascent and evolving colorectal cancer metastases to the liver

GOBIERNO DE NAVARRA (Colaborativos 2020)

ARRASATE IRAGUI, MONTSERRAT

Identificación de dianas terapéuticas para la enfermedad de Parkinson basadas en la interacción de la neuroinflamación y la expresión de sinucleína

GOBIERNO DE NAVARRA (Colaborativos 2020)

BERASAIN LASARTE, MARIA DEL CARMEN

Desarrollo de algoritmos de respuesta al tratamiento nutricional frente a la EHGNA: integración de datos mediante inteligencia artificial

GOBIERNO DE NAVARRA (Colaborativos 2020)

ORTIZ DE SOLÓRZANO AURUSA, CARLOS

Desarrollo nanotecnológico de antimicrobianos innovadores y su evaluación farmacológica mediante dispositivos microfluídicos “airway on a chip”

GOBIERNO DE NAVARRA (Colaborativos 2020)

CORTÉS DOMÍNGUEZ, IVÁN

Desarrollo de un sistema microfluídico para el aislamiento y enriquecimiento de células tumorales circulantes (CTCs) en biopsia líquida

GOBIERNO DE NAVARRA (Colaborativos 2020)

RODRÍGUEZ MADOZ, JUAN ROBERTO

Desarrollo y evaluación de inmunoterapia celular mediante CART alogénicas para el tratamiento de la Leucemia Mieloide Aguda

GOBIERNO DE NAVARRA (Colaborativos 2020)

LÓPEZ SALAZAR, MARIA BEGOÑA

Caracterización de un perfil de biomarcadores no invasivos asociados a daño Cardiaco en pacientes infEctados por SARS-CoV-2. Implicaciones diagnósticas y pronósticas.

GOBIERNO DE NAVARRA (Colaborativos 2020)

ORBE LOPATEGUI, JOSUNE

Caracterización de la NADPH oxidasa 5 como diana terapeutica en el ictus

GOBIERNO DE NAVARRA (Colaborativos 2020)

RODRÍGUEZ GARCÍA, JOSE ANTONIO

Identificación de nuevas dianas y desarrollo de alternativas terapéuticas para el tratamiento de la endocarditis infecciosa

GOBIERNO DE NAVARRA (Colaborativos 2020)

HERVÁS STUBBS, SANDRA

IDENTIFICACION Y DESARROLLO DE TCR TRANSGÉNICOS PARA TERAPIA CELULAR ADOPTIVA DE TUMORES SÓLIDOS

MEMORIA CIENTÍFICA 2020/21 63

PROYECTOS NACIONALES

FINANCIADOR

INVESTIGADOR PRINCIPAL

TÍTULO COMPLETO

GOBIERNO DE NAVARRA (Colaborativos 2020)

GN2020 CENTROS AUDITORÍA PROYECTOS

GOBIERNO DE NAVARRA (Empresas 2020)

ARANGUREN LÓPEZ, XABIER

Quimerismo inter-especie y edición génica en embriones de cerdo: QuimPig

GOBIERNO DE NAVARRA (Doctorados Industriales 2021-2022)

GARITANO LARREA, NEREA

Desarrollo de nanopartículas de CRISPR para el tratamiento del remodelado adverso en la cardiomiopatía isquémica

GOBIERNO DE NAVARRA (Estrategicos 2021)

GONZÁLEZ MIQUEO, ARANZAZU

Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia Cardíaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra)-II (MINERVA-II)

GOBIERNO DE NAVARRA (Estrategicos 2021)

FORTES ALONSO, MARIA PURIFICACIÓN

Utilización de datos genómicos para generar una vacuna contra el cáncer (BLANCA: Breast Long non coding ANti-Cancer Antigens)

GOBIERNO DE NAVARRA (Estrategicos 2021)

PINEDA LUCENA, ANTONIO ÁNGEL

Aplicaciones del estudio multi-ómico de la microbiota al desarrollo de soluciones biotecnológicas innovadoras en el área de la salud (microBiomics)

Gob. Navarra Dep. Educación (Predoctorales)

AGUADO ALVARO, LAURA PILAR

IDENTIFICATION OF NEW MOLECULAR TARGETS INVOLVED IN THE DEVELOPMENT OF ADVERSE CARDIAC REMODELING

Gob. Navarra Dep. Educación (Predoctorales)

DIAZ MAZQUIARAN, AINTZANE

GNE 2020 PREDOC AINTZANE DIAZ F. PROSPER

Gob. Navarra Dep. Educación (Predoctorales)

GONZALEZ BURGOS, IRENE

GNE 2020 PREDOC IRENE GONZALEZ M.VALENCIA

Gob. Navarra Dep. Educación (Predoctorales)

OCHOA MARTÍNEZ, JOSÉ ÁNGEL

GNE 2020 PREDOC JOSE ANGEL OCHOA M. VALENCIA

Gob. Navarra Dep. Educación (Predoctorales)

GOÑI ECHEVERRIA, ENRIQUE

GNE 2020 ENRIQUE GOÑI M. HUARTE Y M. HERNAEZ

Gob. Navarra Dep. Salud/FEDER (Proyectos I+D COVID)

SÁEZ OCHOA, BORJA

Studying the Effect of the Presence of Clonal Hematopoiesis on the Pathogenesis of COVID-19

ISCIII/FEDER (Proyectos I+D)

ARANDA VEGA, FERNANDO

Inmunoterapia experimental en la carcionomatosis peritoneal de cáncer de ovario: enfoque local, mecanismos inmunológicos y hallazgo de biomarcadores

ISCIII/FEDER (Proyectos I+D)

SAEZ OCHOA, BORJA

Papel de la hematopoiesis clonal en el declive funcional del organismo asociado a la edad: la enfermedad pulmonar crónica como modelo de estudio

ISCIII/FEDER (Proyectos I+D)

SAROBE UGARRIZA, PABLO

Diseño de inmunoterapias de combinación frente al hepatocarcinoma basadas en el perfil genómico e inmunológico

ISCIII/FEDER (Proyectos I+D)

SMERDOU PICAZO, CRISTIAN

Terapia génica del cáncer colorrectal utilizando un vector de RNA autorreplicativo para expresar inhibidores de adhesión y migración tumoral en combinación con anticuerpos inmunoestimuladores

ISCIII/FEDER (Proyectos I+D)

PIO OSES, RUBEN

Modulating the complement system to improve the antitumor activity and attenuate the side effects of lung cancer immunotherapy

ISCIII/FEDER (Proyectos I+D)

PASTOR RODRIGUEZ, FERNANDO

Inmunoedición antigénica regulada por “Nonsense Mediated MRNA Decay”: una nueva posibilidad para la inmunoterapia del cáncer

ISCIII/FEDER (Proyectos I+D)

SAN JOSË ENÉRIZ, EDURNE

Terapia epigenética diferenciadora e innovadora para la cura de la Leucemia Mieloide Aguda

ISCIII/FEDER (Proyectos I+D)

RAVASSA ALBÉNIZ, SUSANA

Identificación de una huella molecular basada en biomarcadores en la insuficiencia cardiaca con enfermedad renal crónica. Implicaciones mecanisticas, pronosticas y terapéuticas

ISCIII/FSE (PFIS)

BERRAONDO LÓPEZ, PEDRO

IdiSNA-FIS2020 FIMA ANGELA BELLA CARREÑO

ISCIII/FSE (PFIS)

MONTUENGA BADÍA, LUIS

IdiSNA FIS2020 FIMA MIRARI ECHEPARE TABERNA

Cima Universidad de Navarra 64

PROYECTOS NACIONALES

FINANCIADOR

INVESTIGADOR PRINCIPAL

TÍTULO COMPLETO

MCIU (Predoctoral FPU)

RODRÍGUEZ MÁRQUEZ, PAULA

FPU 2019 PAULA RODRIGUEZ MÁRQUEZ JRRM-JJL

MCIU/AEI/FEDER (Proyectos I+D Retos-Colaboración)

MELERO BERMEJO, IGNACIO JAVIER

Ensayo clínico fase I/II: nuevo enfoque terapéutico para el tratamiento de tumores sólidos con metástasis hepática

MCIU/AEI/FSE (Ramón y Cajal)

TEIJEIRA SÁNCHEZ, ÁLVARO

RYC2019-026406-I ALVARO TEIJEIRA SÁNCHEZ