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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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Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.

Palladino C, Navarro Gomez ML, Soler-Palacin P, Gonzalez-Tome MI, Jiménez de Ory S, Espiau M, Pérez-Hoyos S, León-Leal JA, Méndez M, Moreno-Pérez D, Fortuny C, uer A, Pocheville I, Moreno S, Briz V, on behalf of the CoRISpe Working Group. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AIDS 2015; 29-16, pp.2155-2159. (A; FI= 4,407; Q1 Infectious Disease).

PUBMED DOI

Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.

Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. J Med Virol. 2015 Nov;87(11):1934-9. Epub 2015 May 29.

PUBMED DOI

Relative telomere length impact on mortality of COVID-19: sex differences.

Virseda-Berdices A, Concostrina-Martinez L, Martínez-González O, Blancas R, Resino S, Ryan P, De Juan C, Moreira-Escriche P, Martin-Vicente M, Brochado-Kith O, Blanca-López N, Jiménez-Sousa MA (‡,*), Fernández-Rodríguez A (‡). Relative telomere length impact on mortality of COVID-19: sex differences. J Med Virol 2023; 98 (1): e28368 (A; FI= 20.96; D1, Virology; JCR 2021).

PUBMED

Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide

García-Quintanilla, M., Pulido, M. R., Moreno-Martínez, P., Martín-Peña, R., López-Rojas, R., Pachón, J. and McConnell, M.J.* Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide. Antimicrobial Agents and Chemotherapy 2014. May;58(5):2972-5.

PUBMED DOI

Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors

Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors. González N, McKee K, Lynch RM, Georgiev IS, Jimenez L, Grau E, Yuste E, Kwong PD, Mascola JR, Alcamí J. PLoS One. 2018;13:e0193773.

PUBMED DOI

Diverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain

Delgado E, Benito S, Montero V, Cuevas MT, Fernández-García A, Sánchez-Martínez M, García-Bodas E, Díez-Fuertes F, Gil H, Cañada J, Carrera C, Martínez-López J, Sintes M, Pérez-Álvarez L, Thomson MM; Spanish Group for the Study of New HIV Diagnoses. Diverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain. Front Microbiol. 2019; 3;10:655.

PUBMED DOI

Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier.

Díez-Fuertes F, Delgado E, Vega Y, Fernández-García A, Cuevas MT, Pinilla M, García V, Pérez-Álvarez L, Thomson MM. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother. 2013; 68:1471-1485.

PUBMED DOI

Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections.

Pérez-Álvarez L, Delgado E, Vega Y, Montero V, Cuevas T, Fernández-García A, García-Riart B, Pérez-Castro S, Rodríguez-Real R, López-Álvarez MJ, Fernández-Rodríguez R, Lezaun MJ, Ordóñez P, Ramos C, Bereciartua E, Calleja S, Sánchez-García AM, Thomson MM. Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections. J Antimicrob Chemother. 2014; 69:246-253.

PUBMED DOI

Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia.

Shcherbakova NS, Shalamova LA, Delgado E, Fernández-García A, Vega Y, Karpenko LI, Ilyichev AA, Sokolov YV, Shcherbakov DN, Pérez-Álvarez L, Thomson MM. Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia. AIDS Res Hum Retroviruses. 2014; 30:912-919.

PUBMED DOI

Epidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations.

Vega Y, Delgado E, Fernández-García A, Cuevas MT, Thomson MM, Montero V, Sánchez M, Sánchez AM, Pérez-Álvarez L; Spanish Group for the Study of New HIV-1 Diagnoses in Galicia and Basque Country. Epidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations. PLoS One. 2015; 10:e0125699.

PUBMED DOI

Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe.

Delgado E, Cuevas MT, Domínguez F, Vega Y, Cabello M, Fernández-García A, Pérez-Losada M, Castro MÁ, Montero V, Sánchez M, Mariño A, Álvarez H, Ordóñez P, Ocampo A, Miralles C, Pérez-Castro S, López-Álvarez MJ, Rodríguez R, Trigo M, Diz-Arén J, Hinojosa C, Bachiller P, Hernáez-Crespo S, Cisterna R, Garduño E, Pérez-Álvarez L, Thomson MM. Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe. PLoS One. 2015; 10:e0143325.

PUBMED DOI

Identification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain.

Fernández-García A, Delgado E, Cuevas MT, Vega Y, Montero V, Sánchez M, Carrera C, López-Álvarez MJ, Miralles C, Pérez-Castro S, Cilla G, Hinojosa C, Pérez-Álvarez L, Thomson MM. Identification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain. PLoS One. 2016; 11:e0148549.

PUBMED DOI

Sequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes

Vega Y, Delgado E, de la Barrera J, Carrera C, Zaballos Á, Cuesta I, Mariño A, Ocampo A, Miralles C, Pérez-Castro S, Álvarez H, López-Miragaya I, García-Bodas E, Díez-Fuertes F, Thomson MM. Sequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes. PLoS One. 2016; 11:e0158525.

PUBMED DOI

HIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant.

Karamov E, Epremyan K, Siniavin A, Zhernov Y, Cuevas MT, Delgado E, Sánchez-Martínez M, Carrera C, Kornilaeva G, Turgiev A, Bacqué J, Pérez-Álvarez L, Thomson MM. HIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant. AIDS Res Hum Retroviruses. 2018; 34:629-634.

PUBMED DOI

Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries.

Díez-Fuertes F, Cabello M, Thomson MM. Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries. Infect Genet Evol. 2015; 33:197-205.

PUBMED DOI

Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.

Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.

PUBMED DOI

Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.

Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).​

DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.

Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.

Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients

Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3

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 .