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Investigación
Malaria and Emerging Parasitosis
Líneas de investigación
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Patogénesis e inmunidad viral
A) Desarrollo de metodología point of care frente a hepatitis virales en el reservorio del VIH
El tratamiento precoz de las hepatitis virales reduce el deterioro progresivo del hígado y evita el trasplante hepático. Resulta esencial disponer de métodos diagnóstico rápido, sencillos y coste-efectivos, para el cribado, en la vigilancia epidemiológica y el diagnóstico virológico temprano de enfermedades virales hepáticas. Línea de investigación llevada a cabo en colaboración con el Dr. Ricardo Madrid (BioAssays S.L).
B) Impacto de la coinfección y eliminación de las hepatitis virales en el reservorio del VIH
La coinfección por el VHC impacta en el reservorio del VIH, principal obstáculo para eliminar esta infección. Se realizan distintos abordajes del estudio del reservorio del VIH en pacientes VIH+ con distinta exposición al VHC, y tras su eliminación espontánea o con antivirales de acción directa, con el objetivo de identificar y proponer nuevas estrategias de eliminación/curación del VIH. Esta línea de Investigación se desarrolla en el seno del Grupo Multidisciplinar COVIHEP (COinfección por VIH y HEPatitis).
C) Identificación de marcadores de senescencia inducida por virus y estrategias paliativas
Las infecciones virales inducen una senescencia acelerada cuyo impacto afecta a la evolución de la enfermedad y a posibles comorbilidades. Nuestro objetivo es profundizar en los mecanismos que desencadenan la inmunosenescencia y estrés oxidativo asociado a infecciones virales e identificar nuevas estrategias terapéuticas que palien el envejecimiento prematuro en estos pacientes.
D) Impacto de SARS-CoV-2 en la infección por el VIH y hepatitis virales
Se desconocen las complicaciones a largo plazo de la infección por SARS-CoV-2 en personas que viven con VIH y/o hepatitis virales que podrían experimentar un desarrollo clínico de la enfermedad más desfavorable. La identificación de biomarcadores de gravedad no invasivos (como en sangre/plasma) resulta de especial interés en estos pacientes.
E) Origen y Epidemiología de la enfermedad hepática
Estudio del origen y la dinámica de transmisión espacio-temporal de los virus hepáticos, clave para el entendimiento de su evolución y propagación, así como en el análisis de la carga global de las enfermedades, lo que podría ayudar a desarrollar programas de Salud Pública encaminados a prevenir y frenar su transmisión.
F) Impacto de la viremia de bajo grado del VIH
Se desconoce tanto el origen como los mecanismos de la viremia de bajo grado, presente entre el 3 y 16% que las personas que viven con VIH. Su presencia podría desembocar en un mayor riesgo de sufrir comorbilidades relacionadas con enfermedades cardiovasculares, cáncer y trastornos metabólicos.
G) Calidad del aire y su impacto en poblaciones vulnerables
La contaminación del aire agrava las patologías infecciosas y la salud cardiovascular y respiratoria. La evolución de la enfermedad en personas con enfermedades crónicas con VIH y hepatitis puede verse agravada tras la inhalación continua de contaminantes ambientales. Línea de investigación llevada a cabo en colaboración con el CNSA y el CNE del ISCIII.
H) Coinfección por VHE y protistas entéricos en el reservorio humano y animal: vigilancia e investigación
La coinfección entre virus y protistas entéricos podría influir en la cotransmisión y patogenicidad de dichas especies. Línea de investigación, bajo el concepto “One Health” que se centra en la vigilancia y estudio de la coinfección del VHE y protistas entéricos. Colaboración con el grupo multidisciplinar COHEPROEN (COinfección HEpatitis y PROtistas ENtéricos).
Publicaciones destacadas
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 DOIMycobacterium 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.
DOIMycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter.
9. Muñoz-Sanz A, Rodríguez Vidigal FF, Vera-Tome A, Jimenez MS. Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter. Enfer Infecc Microbiol Clin. 2013; 31:59-6
PUBMED DOIMeasles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.
2. Gil H, Fernández-García A*, Mosquera MM, Hübschen JM, Castellanos AM, de Ory F, Masa-Calles J, Echevarría JE.Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain. PLoS One. 2018 Jul. 16;13(7):e0199975. * Corresponding author.
PUBMED DOIIsolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus
3. Banyard AC, Selden D, Wu G; Thorne L, Jennings D, Marston D, Finke S, Freuling CM, Mueller T, Echevarria JE, Fooks AR. Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus. Journal of General Virology, 2018. 99(12):1590-1599
PUBMED DOIShift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population
6. López-Perea N, Masa-Callesa J, Torres de Miera MV, Fernández-García A, Echevarría JE, de Ory F, Martínez de Aragón MV. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine, 2017, 35(34): 4339-4345.
PUBMED DOIThe Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years
2. Trento A, Rodriguez-Fernandez R, Gonzalez-Sanchez MI, Gonzalez-Martinez F, Mas V, Vazquez M, et al. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years. Front Microbiol. 2017;8:2301.
PUBMED DOIPotent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.
3. Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun. 2017;8:14158.
PUBMED DOIRapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors
6. Gilman MS, Castellanos CA, Chen M, Ngwuta JO, Goodwin E, Moin SM, et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol. 2016;1(6).
PUBMED DOICharacterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
8. Gilman MS, Moin SM, Mas V, Chen M, Patel NK, Kramer K, et al. Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog. 2015;11(7):e1005035.
PUBMED DOIPolyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.
9. Palomo C, Mas V, Vazquez M, Cano O, Luque D, Terron MC, et al. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology. 2014;460-461:119-27.
PUBMED DOIBiophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus
Jiménez-Zaragoza M., Yubero M.L., Martín-Forero E., Castón J.R., Reguera D., Luque D.*, de Pablo P.J., Rodríguez J.M. 2018. Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus. eLife 7: e37295. *Corresponding author.
PUBMED DOIAcquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses
Mata C.P., Luque D., Gómez-Blanco J., Rodríguez J.M., González J.M., Suzuki N., Ghabrial S.A., Carrascosa J.L., Trus B.L., Castón J.R. 2017. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 13(12):e1006755.
PUBMED DOIStructural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes
Sarker S., C. Terrón M., Khandokar Y., Aragão D., Hardy J.M., Radjainia M., Jiménez-Zaragoza M., de Pablo P.J., Coulibaly F., Luque D., Raidal D.R., Forwood J.K. 2016. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nat. Commun. 7:13014. IF: 12.124; D1.
PUBMED DOIHeterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1
Luque D., Mata C.P., González-Camacho F., González J.M., Gómez-Blanco J., Alfonso C., Rivas G., Havens W.M., Kanematsu S., Suzuki N., Ghabrial S.A., Trus B.L., Castón J.R. 2016. Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1. J Virol. 90(24):11220-11230. IF: 4.666, Q1.
PUBMED DOISelf-assembly and characterization of small and monodisperse dye nanospheres in a protein cage
Luque D., de la Escosura A., Snijder J., Brasch M., Burnley R.J, Koay M.S.T., Carrascosa J.L., Wuite G.J.L., Roos W.H., Heck A.J.R., J.J.L.M Cornelissen, Torres T., Castón J.R. 2014. Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage. Chem. Sci.,5, 575-581. IF: 9.211, D1.
DOICryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.
Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1
PUBMED DOINew insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage
Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.
PUBMED DOIEfficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates.
3. Lameijer M, Binderup T, van Leent M, Senders M, Fay F. Seijkens T, Kroon J, Stroes E, Kjaer A, Ochando J, Reiner T, Pérez-Medina C, Calcagno C, Fischer E, Zhang B, Temel R, Swirski F, Nahrendorf M, Fayad Z, Lutgens E, Mulder W and Duivenvoorden R. Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates. Nature Biomedical Engineering. 2018. 2: 279–292.
PUBMED DOINeutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.
4. Braza MS, Conde P, Garcia MR, Cortegano I, Brahmachary M, Pothula V, Fay F, Boros P, Werner SW, Ginhoux F, Mulder WJ, and Ochando J. Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance. Am J Transplant. 2018.
PUBMED DOIDC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance
9. Conde P, Rodriguez M, van der Touw W, Jimenez A, Burns M, Miller J, Brahmachary M, Chen HM, Boros P, Rausell-Palamos F, Yun TJ, Riquelme P, Rastrojo A, Aguado B, Stein-Streilein J, Tanaka M, Zhou L, Zhang J, Lowary TL, Ginhoux F, Park CG, Cheong C, Brody J, Turley SJ, Lira SA, Bronte V, Gordon S, Heeger PS, Merad M, Hutchinson J, Chen SH, Ochando J. 2015. DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance. Immunity. 16;42(6):1143-58.
PUBMED DOIProteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis
2.- Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis. Antonio Infantes-Lorenzo, Jose; Moreno, Inmaculada; Angeles Risalde, Maria; et ál. CLINICAL PROTEOMICS Volumen: 14 Número de artículo: 36 Fecha de publicación: NOV 2 2017
PUBMED DOIFunctional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications.
3.- Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications. Subias Hidalgo, Marta; Yebenes, Hugo; Rodriguez-Gallego, Cesar; et ál..EUROPEAN JOURNAL OF IMMUNOLOGY Volumen: 47 Número: 3 Páginas: 504-515 Fecha de publicación: MAR 2017
PUBMED DOIImmunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot
5.- Immunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot. Churchward, Colin P.; Rosales, Ruben S.; Gielbert, Adriana; et ál..JOURNAL OF PHARMACY AND PHARMACOLOGY Volumen: 67 Número: 3 Número especial: SI Páginas: 364-371 Fecha de publicación: MAR 2015
PUBMED DOIEfficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis.
6.- Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis. Corral, M. Jesus; Serrano, Dolores R.; Moreno, Inmaculada; et ál..JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Volumen: 69 Número: 12 Páginas: 3268-3274 Fecha de publicación: DEC 2014
PUBMED DOIA Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models
7.- A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models. Subias, Marta; Tortajada, Agustin; Gastoldi, Sara; et ál..JOURNAL OF IMMUNOLOGY Volumen: 193 Número: 11 Páginas: 5567-5575 Fecha de publicación: DEC 2014
PUBMED DOIDetection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test
8.- Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test. Moreno, Inmaculada; Alvarez, Julio; Garcia, Nerea; et ál..VETERINARY PARASITOLOGY Volumen: 199 Número: 3-4 Páginas: 264-267 Fecha de publicación: 2014
PUBMED DOIEvidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain.
9.- Evidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain. Garcia, Nerea; Moreno, Inmaculada; Alvarez, Julio; et ál..BIOMED RESEARCH INTERNATIONAL Número de artículo: 318254 Fecha de publicación: 2014
PUBMED DOIMucus-Activatable Shiga Toxin Genotype stx2d in Escherichia coli O157:H7
2. Sánchez, S., Llorente, M.T., Herrera-León, L., Ramiro, R., Nebreda, S., Remacha, M.A., Herrera-León, S. Mucus-activatable shiga toxin genotype stx2d in Escherichia coli O157:H7. (2017) Emerging Infectious Diseases, 23 (8), pp. 1431-1433.
PUBMED DOIMultinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015
3. Fonteneau, L., Da Silva, N.J., Fabre, L., Ashton, P., Torpdahl, M., Müller, L., Bouchrif, B., El Boulani, A., Valkanou, E., Mattheus, W., Friesema, I., Herrera Leon, S., Varela Martínez, C., Mossong, J., Severi, E., Grant, K., Weill, F., Gossner, C.M., Bertrand, S., Dallman, T., Le Hello, S. Multinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015. (2017) Eurosurveillance, 22 (7).
PUBMED DOIProspective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis
4. Inns, T., Ashton, P.M., Herrera-Leon, S., Lighthill, J., Foulkes, S., Jombart, T., Rehman, Y., Fox, A., Dallman, T., De Pinna, E., Browning, L., Coia, J.E., Edeghere, O., Vivancos, R. Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis (2017) Epidemiology and Infection, 145 (2), pp. 289-298.
PUBMED DOIPlasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases.
5. Herrera-Leon, S., Llorente, M.T., Sanchez, S. Plasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases. (2016) Antimicrobial Agents and Chemotherapy, 60 (3), pp. 1950-1951.
PUBMED DOIMolecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014.
6. Eibach, D., Herrera-León, S., Gil, H., Hogan, B., Ehlkes, L., Adjabeng, M., Kreuels, B., Nagel, M., Opare, D., Fobil, J.N., May, J. Molecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014. (2016) PLoS Neglected Tropical Diseases, 10 (5).
PUBMED DOIInformación adicional
Despite progress, parasitic diseases remain a major challenge for humans. Its rapid and accurate detection, as well as the identification of specific genes related to virulence and/or resistance to treatments, is a necessity for management and planning control strategies.
The main objective of the group is to carry out quality, competitive and innovative research, to acquire, disseminate and apply in clinical parasitology with the ultimate goal of improving and innovating in the diagnoses, therapies and control of parasitic diseases. This general objective is implemented through external projects and collaborations with different funding sources:
- Characterization of submicroscopic malaria. National Hospital Network. (FIS-ISCIII).
- Design, optimization and validation of advanced diagnostic methods for the detection of blood parasites (Retos-MICINN).
- Control of onchocerciasis in Equatorial Guinea. CNMTrop-ISCIII (Task Force, USA).
- Characterization and control of Mansonellosis and Onchocerciasis in the Amazon region in Brazil. FIOCRUZ from Amazonas, Brazil. (Cpnqt-Brazil).
- Plasmodium knowlesi and its implication as the fifth species of human malaria. MRC, Malaysia.
- Intestinal parasitosis in Egypt from Cryptosporidium (protozoan) to Capillaria (Nematode). Cairo University and Al-Azhar University, Egypt. (MHESR, AECID).