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Investigation
Immunobiology
Research Lines
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Hepatitis
- Diseño de métodos diagnósticos para el estudio de los virus de las hepatitis (VH) A, B, C, D, E: Diseñamos sistemas de PCR para su detección y caracterización.
- Evaluación de métodos diagnósticos de los VH. Colaboramos con empresas para estudios de sensibilidad y especificidad de equipos diagnósticos.
- Estudios de Seroprevalencia de los virus de las hepatitis.
- Epidemiología genómica de genomas completos de VHA, VHB, VHC, VHD y VHE en colaboración con el ECDC. Estudios de trazabilidad del VHE.
- Caracterización molecular de virus de las hepatitis mediante secuenciación masiva: a) VHB: mutantes de escape HBsAg (prevalencia y efectos en la detección del HBsAg). Estudio de mutaciones en epítopos de estimulación inmune y mutaciones asociadas a evolución clínica desfavorable.
- b) VHC: resistencias a los antivirales de acción directa. Análisis molecular de subtipos poco frecuentes.
c) Estudios filogenéticos del VHD.
d) Análisis genómico del VHE.
e) Investigación etiológica de hepatitis no filiadas mediante estudios de metagenómica.
- b) VHC: resistencias a los antivirales de acción directa. Análisis molecular de subtipos poco frecuentes.
Research projects
Content with Investigacion .
1. Proyecto CIBEREPS 2022. Microbiological and genomic investigation of hepatitis in children by metagenomic approach in case and control subjects (IP: Ana Avellón).
2023-2024. En colaboración con el Hospital San Joan de Deu de Barcelona.
2. MPY 501-19: Tracking hepatitis E virus infection by means of epidemiological research and whole genome sequencing. Project TrazHE. (IP: Ana Avellón). 2020-2024.
3. Proyecto CIBEREPS 2021 Metagenomic sequencing to identify viral aetiologies in undiagnosed paediatric cases of meningitis and encephalitis (IP: D. Tarragó). 2021-2022.
4. MPY 383/19 (PEJ2018-004446-A). Ayudas para la promoción de empleo joven e implantación de la garantía juvenil en I+D+I. análisis de la complejidad de secuencias de los virus de la hepatitis A, B, C; D y E (VHA, VHB, VHC, VHD y VHE) mediante técnicas de secuenciación masiva. (IP: Ana Avellón). 2020-2021.
5. MPY 1285/16 Movilidad "Salvador de Madariaga" programa estatal de promoción de talento y su empleabilidad. (IP: Ana Avellón). 2016.
Publications
Inhibition of LpxC increases antibiotic susceptibility in Acinetobacter baumannii.
8. García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell M.J.* Inhibition of LpxC increases antibiotic susceptibility in Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy. 2016 Jul 22;60(8):5076-9.
PUBMED DOIImmunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection.
9. García-Quintanilla M., Pulido M.R., Pachón J. and McConnell, M.J.* Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection. PLOS One. 2014 Dec 8;9(12).
PUBMED DOIEncephalitis associated with human herpesvirus-7 infection in an immunocompetent adult.
M. Parra; A. Alcala; C. Amoros; A. Baeza; A. Galiana; D. Tarragó; M.Á. García-Quesada; V. Sánchez-Hellín. Encephalitis associated with human herpesvirus-7 infection in an immunocompetent adult. Virology Journal. 14 - 1, 2017.
PUBMED DOIMolecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain.
M. Cabrerizo; M. Díaz-Cerio; C. Muñoz-Almagro; N. Rabella; D. Tarragó; M.P. Romero; M.J. Pena; C. Calvo; S. Rey-Cao; A. Moreno-Docón; I. Martínez-Rienda; A. Otero; G. Trallero. Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain. J Med Virol. 2017 Mar;89(3):435-442.
PUBMED DOIViral epidemic outbreaks and public health alerts studied at the National Centre of Microbiology during a two-year period (2012-2013).
J.M. Echevarría Mayo; A.A. Avellón Calvo; M. Cabrerizo Sanz; I. Casas Flecha; J.E. Echevarría Mayo; Fd.eO. de Ory Manchón; A. Negredo Antón; F. Pozo Sánchez; M.P. Sánchez-Seco Fariñas; D. Tarragó Asensio; G. Trallero Masó. Viral epidemic outbreaks and public health alerts studied at the National Centre of Microbiology during a two-year period (2012-2013). Revista española de salud pública. 90, pp. E16 - E16. 2016
PUBMEDAdditional Information
Doctoral theses
“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.” Carolina Ruiz Sánchez. Complutense University of Madrid, 2022
Master's thesis
Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024
Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023
Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023
Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022
Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022
Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020
Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020
B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020
Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018
Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018
Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017
Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017
Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017
Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016
Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015
Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015
Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015
Final degree projects
Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021
Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021
Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.
Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.
Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014
Teaching in training courses
Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)
Outreach / Citizen Science
• Collaboration in the 4th+Company CAM program.
• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII
• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”
Doctoral theses
“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.” Carolina Ruiz Sánchez. Complutense University of Madrid, 2022
Master's thesis
Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024
Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023
Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023
Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022
Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022
Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020
Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020
B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020
Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018
Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018
Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017
Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017
Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017
Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016
Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015
Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015
Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015
Final degree projects
Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021
Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021
Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.
Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.
Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014
Teaching in training courses
Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)
Outreach / Citizen Science
• Collaboration in the 4th+Company CAM program.
• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII
• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”
The current director of CNM is Dr. José Miguel Rubio Muñoz.
Dr. José Miguel Rubio has a degree in Biological Sciences from the Universidad Autónoma de Madrid (1986) and a PhD in Biological Sciences from the same university (1992). He carried out his doctoral thesis at the Department of Genetics of the Universidad Autónoma de Madrid, as Associate Professor (1988-1989), and at the School of Biology of the University of East Anglia in Norwich, UK, as Senior Research Assistant (1989-1992).
During his postdoctoral period he obtained a grant from the European Commission within the Human Capital and Mobility Program to be carried out at the University of “La Sapienza” in Rome, Italy and the Institute of Molecular Biology and Biotechnology in Crete, Greece (1993-1994). Subsequently, he made a further stay funded by the WHO and the university itself at the Department of Entomology, Wageningen University, The Netherlands (1994-1996).
Since 1997 he has been a member of the Instituto de Salud Carlos III (ISCIII), where he joined the Department of Parasitology of the National Center of Microbiology, as an EU-INCO postdoctoral fellow and later with a grant from the Autonomous Community of Madrid (CAM). She was part of the founding group of the National Center for Tropical Medicine (2003-2006) and of the 24/7 Alerts and Emergencies Unit (2006-2018) and is currently Head of the Malaria and Emerging Parasitosis Unit of the National Microbiology Center and is part, as research staff, of the Center for Biomedical Research Network on Infectious Diseases (CIBERINFEC/ISCIII).
During his scientific career he has been Visiting Scientist at the Leonidas e Marie Dean Center (FIOCRUZ-AMAZONAS, Manaus, Brazil) and is an External Consultant of the Parasitology Departments of Cairo University (Egypt) and the Medical Research Center (MRC) of Kuala Lumpur (Malaysia). He also belongs or has belonged to different national and international committees: Member of the expert group for malaria control of the European Centre for Disease Control (ECDC) since 2011; Expert-Evaluator for health programs of the European Commission since 2004; Spanish Representative (commissioned by ISCIII and MSC) in the Technical Scientific Committee of the TDR (WHO) 2007-2008; Spanish Deputy Focal Point for microbiology at the European Centre for Disease Control (ECDC) from 2012 to 2020; and, member of the Research Ethics Committee of ISCIII until 2019.
In this period he has published more than 100 articles in international indexed journals, 10 book chapters and has been co-editor of two books in the area of malaria, tropical medicine and neglected diseases. He has participated in 58 competitively funded research projects, 20 of them international, having been the principal investigator in 8 national and 11 international projects as PI of the project or WP leader. In addition, he has led five agreements with companies. Currently he has been awarded four sexenios of research, being presented this year 2025 to the fifth. In the teaching field, he participates in different postgraduate programs in the areas of microbiology and parasitology, having directed seven doctoral theses and more than 20 Master's or Degree final projects, both nationally and internationally.
El laboratorio de Referencia e Investigación en Resistencia a Antibióticos ofrece una amplia cartera de servicios al Sistema Nacional de Salud, las cuales pueden solicitarse en cnm-laboratorios.isciii.es. Jefe del Laboratorio: Jesús Oteo Iglesias (Punto focal Nacional de Resistencia antibiótica).
Dispone de dos programas de Vigilancia oficiales y gratuitos que engloban los ensayos ofertados ya sea como aislamientos individuales o mediante estudio de brotes. El Laboratorio utiliza asimismo técnicas de PCR en tiempo real para la detección de genes de resistencia, estas técnicas se han adaptado a un formato multiplex que permite detectar varios genes en la misma reacción. En los últimos años se han incluido metodologías basadas en la secuenciación de genomas completos para el análisis de bacterias multiresistentes (WGS).
Programa de vigilancia de Haemophilus influenzae. Responsables: María Pérez Vázquez (Punto focal Nacional de Haemophilus influenzae) y Belén Aracil. Laboratorio encargado de la identificación, estudio de sensibilidad y análisis genotípico de aislados de Haemophilus influenzae, centrándose esencialmente en la patología invasiva debida este patógeno.
Programa de vigilancia de Resistencia a Antibióticos. Responsables: María Pérez Vázquez y Belén Aracil (Punto focal Nacional de Resistencia antibiótica). Laboratorio encargado de la identificación, el estudio de sensibilidad antibiótica, y el diagnóstico fenotípico y genotípico de los diferentes mecanismos de resistencia a antibióticos fundamentalmente en enterobacterias y gram-negativos no fermentadores y Enterococcus spp.
Estudio de brotes. Responsables: Belén Aracil y María Pérez Vázquez. El programa incluye la caracterización de brotes nosocomiales y clones emergentes de alto riesgo mediante diferentes técnicas moleculares (tabla resumen). Éstas, nos permiten realizar estudios filogenéticos con el fin de obtener una información detallada acerca la relación entre los diferentes aislados y su trazabilidad. El objetivo final es generar datos que se transfieren a los hospitales como ayuda para la prevención o control de la propagación del brote.
Acreditación y Calidad. Responsable: Belén Aracil. El laboratorio Referencia e Investigación en Resistencia a Antibióticos ha sido de los primeros en el ISCIII en la utilización de técnicas acreditadas por la Entidad Nacional de Acreditaciones (ENAC). Este laboratorio consiguió la primera acreditación homologada de técnicas diagnósticas en 2012, programa que ha sido ampliado, de manera que en la actualidad más de la mitad de las técnicas ofrecidas al Sistema Nacional de Salud están debidamente acreditadas por ENAC.
Técnicos responsables de las técnicas realizadas en el Laboratorio: Noelia Lara Fuella y Verónica Bautista Sánchez.
En la siguiente imagen se resumen las técnicas ofrecidas al Sistema Nacional de Salud.
| PROGRAMAS | NOMBRE CARTERA SERVICIO | PATÓGENO | DETERMINACIÓN, DETECCIÓN, ANÁLISIS | MÉTODOS |
|
Programa de vigilancia de Haemophilus Programa de vigilancia de resistencia a antibióticos. |
Identificación bacteriana |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus spp |
Identificación bacteriana |
Bioquímicos MALDI TOF Secuenciación de RNAr |
| | Identificación capsular |
Haemophilus influenzae
|
Identificación capsular fenotípica y genotípica |
Aglutinación serológica en latex PCR ind/multiplex |
| | Determinación de Sensibilidad |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
Determinación de Sensibilidad |
Microdilución Tiras epsilon Kirby Bauer |
| | Métodos fenotípicos de detección de mecanismos de resistencia |
Enterobacterias, gram-negativos no fermentadores,
|
Métodos fenotípicos de detección de mecanismos de resistencia |
Discos y tabletas combinados con inhibidores Tiras combinadas Test de Hodge modificado CabaNP Inmunocromatografía CBP |
| | Métodos genotípicos de detección de mecanismos de resistencia |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
ADN, PCR y secuenciación |
PCR ind/multiplex Análisis comparativo de las secuencias |
| | Tipificación molecular/análisis filogenéticos |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
Corte enzimas de restricción, electroforesis ADN, PCR y secuenciación Preparación de librerías y secuenciación y análisis de genomas completos |
PFGE
MLST
WGS |