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Investigation

Immunobiology

Research Lines

Content with Investigacion Hepatitis .

Hepatitis

  1. 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.
  2. Evaluación de métodos diagnósticos de los VH. Colaboramos con empresas para estudios de sensibilidad y especificidad de equipos diagnósticos.
  3.  Estudios de Seroprevalencia de los virus de las hepatitis.
  4.  Epidemiología genómica de genomas completos de VHA, VHB, VHC, VHD y VHE en colaboración con el ECDC. Estudios de trazabilidad del VHE.
  5. 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.
    1. 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.

Research projects

Content with Investigacion Hepatitis .

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.​

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Publications

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Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study).

5. Alastruey-Izquierdo A, Alcazar-Fuoli L, Rivero-Menéndez O, Ayats J, Castro C, García-Rodríguez J, Goterris-Bonet L, Ibáñez-Martínez E, Linares-Sicilia MJ, Martin-Gomez MT, Martín-Mazuelos E, Pelaez T, Peman J, Rezusta A, Rojo S, Tejero R, Anza DV, Viñuelas J, Zapico MS, Cuenca-Estrella M; the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI. Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study). Antimicrob Agents Chemother. 2018 Aug 27;62(9).

PUBMED DOI

Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

6. Gonçalves SM, Lagrou K, Rodrigues CS, Campos CF, Bernal-Martínez L, Rodrigues F, Silvestre R, Alcazar-Fuoli L, Maertens JA, Cunha C, Carvalho A. Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients. Front Microbiol. 2017 Nov 29;8:2362.

PUBMED DOI

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium

7. Lupiañez CB, Canet LM, Carvalho A, Alcazar-Fuoli L, Springer J, Lackner M, Segura-Catena J, Comino A, Olmedo C, Ríos R, Fernández-Montoya A, Cuenca-Estrella M, Solano C, López-Nevot MÁ, Cunha C, Oliveira-Coelho A, Villaescusa T, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Potenza L, Luppi M, Lass-Flörl C, Loeffler J, Einsele H, Vazquez L; PCRAGA Study Group, Jurado M, Sainz J. Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium. Infect Immun. 2015 Dec 14;84(3):643-57.

PUBMED DOI

Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host.

9. Mesa-Arango AC, Rueda C, Román E, Quintin J, Terrón MC, Luque D, Netea MG, Pla J and Zaragoza O. Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host. Antimicrob. Agents Chemother. 2016. 60(4):2326-35.

PUBMED DOI

The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy

Benavides-Nieto M, Méndez-Echevarría A, Del Rosal T, García-García ML, Casas I, Pozo F, de la Serna O, Lopez-Granados E, Rodriguez-Pena R, Calvo C. The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy. Pediatr Pulmonol. 2019 Feb;54(2):194-199. Indice Impacto: 3,157. Revista en Q1.

PUBMED DOI

Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016.

Broberg EK, Waris M, Johansen K, Snacken R, Penttinen P; European Influenza Surveillance Network. Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016. Euro Surveill. 2018 Feb;23(5). Indice Impacto: 5,983. Revista en Decil 1

PUBMED DOI

Human Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study.

García-García ML, Calvo C, Rey C, Díaz B, Molinero MD, Pozo F, Casas I. Human Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study. PLoS One. 2017 Mar 16;12(3):e0173504. doi: 10.1371/journal.pone.0173504. eCollection 2017. Indice Impacto: 2,766. Revista en Q1.

PUBMED DOI

Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children

Calvo C, Cuevas MT, Pozo F, García-García ML, Molinero M, Calderón A, Gonzalez-Esguevillas M, Pérez-Sautu U, Casas I. Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children. Pediatr Infect Dis J. 2016 Jan;35(1):45-9.

PUBMED DOI

Clinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections.

García-Garcia ML, González-Carrasco E, Quevedo S, Muñoz C, Sánchez-Escudero V, Pozo F, Casas I, Calvo C. Clinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections. Pediatr Infect Dis J. 2015 Jul;34(7):693-9. Indice Impacto: 2,587. Revista en Q1

PUBMED DOI

Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses.

Calvo C, García-García ML, Sanchez-Dehesa R, Román C, Tabares A, Pozo F, Casas I. Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses. PLoS One. 2015 Jul 6;10(7):e0132162. eCollection 2015. Indice Impacto: 3,057. Revista en Q1

PUBMED DOI

Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study

Jiménez-Jorge S, Pozo F, de Mateo S, Delgado-Sanz C, Casas I, García-Cenoz M, Castilla J, Sancho R, Etxebarriarteun-Aranzabal L, Quinones C, Martínez E, Vega T, Garcia A, Giménez J, Vanrell JM, Castrillejo D, Larrauri A, on behalf of the Spanish Influenza Sentinel Surveillance System (SISS). Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study. Euro Surveill. 2014 Mar 6;19(9). Indice Impacto: 5,722. Revista en Q1.

PUBMED DOI

Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors

Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20. Indice Impacto: 5,722. Revista en Q1

PUBMED DOI

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case.

Rodriguez A, Falcon A, Cuevas MT, Pozo F, Guerra S, García-Barreno B, Martinez-Orellana P, Pérez-Breña P, Montoya M, Melero JA, Pizarro M, Ortin J, Casas I, Nieto A. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case. PLoS One. 2013;8(1):e53515. doi: 10.1371/journal.pone.0053515. Epub 2013 Jan 10. Indice Impacto: 3,534. Revista en Q1

PUBMED DOI

Prospective study of influenza C in hospitalized children.

Calvo C, García-García ML, Borrell B, Pozo F, Casas I. Prospective study of influenza C in hospitalized children. Pediatr Infect Dis J. 2013 Aug;32(8):916-9. doi: 10.1097/INF.0b013e31828fca10. Indice Impacto: 3,135. Revista en Q1

PUBMED DOI

Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement.

Gasch O, Meije Y, Espasa M, Font B, Jimenez MS, Fernandez-Hidalgo N. Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol. 2018. Jul

PUBMED DOI

Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006

3. Samper S, Gavin P, Millan-Lou MI, Iglesias M.J. Jimenez MS. Spanish Working Group on MDR-TB, Covin D, Rastogi N. Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006. Infec Genet Evol. 2017. Aug 5;55:117.

PUBMED DOI

Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor.

5. Martinez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Alvarez-Gomez D, Alvarez E, Ferrer Bazaga S, Garcia-Perez A, Ortega F, Angulo-Bartures I, Rullas-Trincado J, Blanco Ruano D, Torres P, Castañeda P, Huss S, Fernandez R, Gonzalez del Valle S, Ballel L, Barros D, Modha S, Dhar N, Signorino-Gelo F, McKinney JD, Garcia-Bustos JF, Lavandera JL, Sacchettini JC, Jimenez MS, Martin-Casabona N, Castro-PIchel J, Mendoza-Losana A. Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor. EBioMedicine. 2016; 8:291-301

PUBMED DOI

Peritoneal tuberculosis due to Mycobacterium caprae.

6. Nebreda T, Alvarez-Prida E, Blanco B, Remacha MS, Samper S, Jimenez MS. Peritoneal tuberculosis due to Mycobacterium caprae. ID Cases 2016; 4:50-52.

PUBMED DOI

Pediatric drug-resistant tuberculosis in Madrid family matters

7. Santiago B, Baquero-Artiago F, Mejias A, Blázquez D, Jimenez MS, Mellado-Peña MJ, EREMITA Study group. Pediatric drug-resistant tuberculosis in Madrid: family matters. The Pediatric Infectious Disease Journal. 2014; 33:345-350.

PUBMED DOI

Mycobacterium kumamotonense, another Member of the Mycobacterium terrae Complex Unusually Carrying Two Copies of the Ribosomal RNA Operon

8. Menéndez MC, Jiménez MS, Yubero J, García MJ. Mycobacterium kumamotonense, another Member of the Mycobacterium terrae Complex Unusually Carrying Two Copies of the Ribosomal RNA Operon. Mycobac Dis; 2014; 4:176.

DOI

Content with Investigacion Hepatitis .

List of staff

Additional Information

Our group is interested in the mechanisms of generation of hematopoietic cells throughout ontogeny and the influence that the first hematopoietic cells, belonging to the innate/pseudoinnate immune system, exert on the adaptive immune system in the adult individual. Our lines of research include the analysis of pseudoinnate lymphoid populations, which connect the innate and adaptive immune systems, and whose origin is in progenitors of early ontogeny. We are trying to understand its role in the immune response through TLR receptors (“Toll-like receptors”) throughout life, particularly in animal models of bacterial infection, with the aim of designing new vaccine therapies. We analyze immune diversity in animal models and in human samples of children and elderly people diagnosed with respiratory disease, by: a) analyzing the lymphoid subpopulations of the local response. b) the study of the genetic rearrangements of the immunoglobulins that are produced. c) the systemic effector response and in peripheral organs. These approaches, carried out both in the mouse model and in human samples, will facilitate the design of more effective therapies and the characterization of biomarkers, adapted to the pediatric and elderly population, useful for the health field and technological innovation.rupo está interesado en los mecanismos de generación de células hematopoyéticas a lo largo de la ontogenia y la influencia que las primeras células hematopoyéticas, pertenecientes al sistema inmune innato/pseudoinnato, ejercen sobre el sistema inmune adaptativo en el individuo adulto. Nuestras líneas de investigación incluyen el análisis de poblaciones linfoides pseudoinnatas, que conectan el sistema inmune innato y adaptativo, y cuyo origen está en progenitores de la ontogenia temprana. Intentamos entender su papel en la respuesta inmune a través de receptores TLR (“Toll-like receptors”) a lo largo de la vida, en particular en modelos animales de infección bacteriana, con objeto de diseñar nuevas terapias vacunales. Analizamos la diversidad inmune en modelos animales y en muestras humanas de niños y ancianos diagnosticados de enfermedad respiratoria, mediante: a) el análisis de las subpoblaciones linfoides de la respuesta local. b) el estudio de los reordenamientos genéticos de las inmunoglobulinas que se producen. c) la respuesta efectora sistémica y en órganos periféricos. Estas aproximaciones, realizadas tanto en el modelo de ratón como en muestras humanas, facilitarán el diseño de terapias más eficaces y la caracterización de biomarcadores, adaptados a la población infantil y envejecida, de utilidad para el ámbito sanitario y de innovación tecnológica.

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”

Content with Investigacion Hepatitis .