Hepatitis C and VIH/VHC coinfection
Research Lines
Content with Investigacion .
Mechanisms of pathogenic fungal host adaptation: Morphogenesis in Cryptococcus neoformans
One of the main mechanisms by which fungi are able to cause disease in humans is their ability to evade the immune response and adapt to the environmental conditions found in the host. In this regard, one of the yeasts that has the greatest ability to adapt to the host is Cryptococcus neoformans. This fungus is found in the environment, and is acquired by inhalation, although the most typical picture is meningitis in immunocompromised patients, mainly HIV+. The main phenotypic characteristic is the presence of a polysaccharide capsule surrounding the cell, which is considered a virulence factor. In addition, C. neoformans is able to increase cell size significantly forming “titan” cells, which can reach a diameter of more than 70 microns. In the laboratory, we are interested in the role of these titan cells in the virulence of C. neoformans. Recently, we have described in vitro media in which C. neoformans forms pseudo-titan cells, which has allowed us to identify new factors and pathways involved in this process.
Mechanisms of action of antifungals
In parallel, we have a line whose main objective is to characterize the mechanisms of action of antifungals. Specifically, we have focused our work on the effect of Amphotericin B (AmB). For decades it has been thought that this antifungal causes cell death after binding to ergosterol and pore formation. Our results indicate that this antifungal also induces strong oxidative stress in the cell, which occurs before cell integrity is lost. Furthermore, we have shown that oxidative stress is necessary for the fungicidal action of AmB. These results open the door to design new strategies to improve its efficiency in patients.
New therapeutic strategies
Work with AmB has led to research aimed at improving antifungal therapies. In particular, we have used the strategy of “off-patent” drug repositioning to search for new activities. Using this approach, we have identified several drugs that increase the effectiveness of AmB against major pathogenic yeasts, such as the antibiotic erythromycin. This approach has allowed us to identify drugs with antifungal activity against emerging pathogens, such as Candida auris.
Research projects
Content with Investigacion .
Projects with public funding
TITLE: Virulence factors of pathogenic yeasts and their influence on the host.
FUNDING ENTITY: Ministry of Education and Science.
POSITION HELD: Principal Investigator, Contracted “Ramón y Cajal”.
START/FINISH: 2006-2007
AMOUNT: 15,000 EUROS
TITLE: Characterization of fungal giant cells and their role during infection in mammals.
FINANCING ENTITY: Instituto de Salud Carlos III
POSITION HELD: Principal Investigator, Contracted “Ramón y Cajal”.
START/FINISH: 2006-2007
AMOUNT: 55,000 EUROS
TITLE: Search and identification of genes involved in the resistance to antifungal agents in
Cryptococcus neoformans
FUNDING ENTITY: Ministry of Science and Innovation.
POSITION HELD: Principal Investigator, Contracted “Ramón y Cajal”.
START/FINISH: 2008-2010
AMOUNT: 25,000 EUROS
COLLABORATORS: Juan Luis Rodríguez Tudela (National Center of Microbiology, ISCIII. Madrid); Manuel Cuenca Estrella (National Center of Microbiology, ISCIII. Madrid); Maria Jose Gianinni (Faculdade de Ciências Farmacêuticas-UNESP). Brazil
TITLE: Role of morphological changes of the pathogenic yeast Cryptococcus neoformans during host infection.
FUNDING ENTITY: Ministry of Science and Innovation. National Plan Program “Non-oriented Fundamental Research”, area of Biomedicine, SAF2008-03761.
POSITION HELD: Principal Investigator, Contracted “Ramón y Cajal”.
START/END: 2009-2011
AMOUNT: 46,000 EUROS
PROJECT TITLE: Identification of the molecular mechanisms involved in the morphogenesis of Cryptococcus neoformans and study of their function during infection.
FUNDING ENTITY: Ministry of Science and Innovation, National Plan for Non-Oriented Fundamental Research, Biomedicine Area, Referencia: SAF2011-25140
DURATION FROM: January 2012 UNTIL: December 2014
PRINCIPAL INVESTIGATOR: Oscar Zaragoza Hernández
This project has an FPI grantee granted.
SUBSIDY: 90.000 euros
TITLE: Importance of morphogenesis in the virulence of pathogenic yeast Cryptococcus neoformans and improvement of amphotericin B-based cryptococcosis therapy. Reference: SAF2014-25140
FUNDING ENTITY: MINECO (Call for R+D+I Projects “RETOS INVESTIGACION)
POSITION HELD: Principal Investigator
START/FINISH: 2015-2017
Funding: 100.000 €.
TITLE: Study of the molecular basis and factors inducing morphological changes in Cryptococcus neoformans and characterization of new therapeutic strategies. Reference: SAF2017-86912-R
FUNDING ENTITY: MINECO (Call for R+D+I Projects “RETOS INVESTIGACION)
POSITION HELD: Principal Investigator
START/END: 2018-2020
Funding: 106.000 €.
TITLE: Mechanisms of adaptation of the pathogenic yeast Cryptococcus neoformans to the lung. Reference: PID2020-114546RB
FUNDING ENTITY: Ministry of Science and Innovation, State Research Agency (Call “Proyectos I+D+I” 2020 - Modalities “Research Challenges” and “Knowledge Generation”).
POSITION HELD: Principal Researcher
START/END: 01/09/2021-31/05/2025
Funding: 143,990 €.
TITLE: Precision medicine against antimicrobial resistance. MePRAM Project.
FUNDING ENTITY: Research Projects on Precision Personalized Medicine of the Strategic Action in Health 2021-2023, under the PERTE for Vanguard Health and charged to the European funds of the Recovery, Transformation and Resilience Plan.
POSITION: Collaborator (Principal Investigator: Jesús Oteo Iglesias)
START/FINISH: 2023-2025
Funding: 4.339.500 €.
TITLE: Centre for Biomedical Research in Network. Infectious Diseases Area (CIBERINFEC)
Funding Agency: Insituto de Salud Carlos III. Reference: CB21/13/00105
Dates: 2022-2026 Funding: 85.000 € (first year)
PI: Emilia Mellado Terrado / CoPI: Óscar Zaragoza Hernández
TITLE: Study of the genetic, metabolic and cellular determinants that influence titan cell formation in the fungal pathogen Cryptococcus neoformans and correlation with antifungal exposure.
CALL FOR PROJECTS: Knowledge Generation Projects.
FUNDING ENTITY. State Research Agency. Ministry of Science, Innovation and Universities.
REFERENCE: Project PID2023-148686OB-I00 Project funded by MICIU/AEI/10.13039/501100011033 and by FEDER, EU.
PRINCIPAL INVESTIGATOR: Oscar Zaragoza Hernández
START/END: 2024-2027
FUNDING: 180.000 €.
TITLE: Characterization of azole-resistant Candida parapsilosis isolates associated with hospital outbreaks: New strategies for their detection and treatment.
CALL: Strategic Action in Intramural Health.
FUNDING ENTITY. Carlos III Health Institute.
REFERENCE: AESI-2024 PI24CIII/00051
PRINCIPAL RESEARCHER: Oscar Zaragoza Hernández / Laura Alcázar Fuoli
START/FINISH: /01/012025-31/12/2027
FUNDING: 70.000 €.
Projects financed by biotechnology companies
PROJECT TITLE: Amphores. Evaluation of the induction of oxidative damage by Amphoterin B in susceptible and resistant yeast species.
FUNDING ENTITY: Gilead
DURATION FROM: 2011 TO: 2012
PRINCIPAL INVESTIGATOR: Oscar Zaragoza Hernández
GRANT: 55,000 euros
TITLE: Fungomics. Evaluation of the activity of amphotericin B and other antifungals against human pathogenic fungi.
FINANCING ENTITY: Gilead
POSITION HELD: Principal Investigator
START/END: 2019-2020
TITLE: Antifungal susceptibility testing of a set of Candida spp to CD101 and anidulafungin in five microdilution plates.
FUNDING ENTITY: Cidara
POSITION HELD: Principal Investigator
START/END: 2018
TITLE: Cidara MultiCentre EUCAST study
FUNDING ENTITY: Cidara
POSITION HELD: Principal Investigator
START/END: 2016
TITLE: Characterization of triazole-resistant Candida parapsilosis isolates from Spanish hospitals
FUNDING ENTITY: Gilead Science
POSITION HELD: Principal Investigator
START/END: 2022-2023
TITLE: EUCAST multicentre MIC testing of manogepix meeting EUCAST ECOFF setting criteria
FUNDING ENTITY: Pfizer
POSITION HELD: Principal Investigator
START/END: 2023
Publications
Lorente, E., E. Barnea, C. Mir, A. Admon, and D. López. 2020. The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase. J Proteomics. 221:103759.
Lorente, E., E. Barnea, C. Mir, A. Admon, and D. López. 2020. The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase. J Proteomics. 221:103759.
PUBMED DOIMarquez, A., M. Gomez-Fontela, S. Lauzurica, R. Candorcio-Simon, D. Munoz-Martín, M. Morales, M. Ubago, C. Toledo, P. Lauzurica, and C. Molpeceres. 2020. Fluorescence enhanced BA-LIFT for single cell detection and isolation. Biofabrication. 12:025019.
Marquez, A., M. Gomez-Fontela, S. Lauzurica, R. Candorcio-Simon, D. Munoz-Martín, M. Morales, M. Ubago, C. Toledo, P. Lauzurica, and C. Molpeceres. 2020. Fluorescence enhanced BA-LIFT for single cell detection and isolation. Biofabrication. 12:025019.
PUBMED DOILorente, E., M. Marcilla, P. G. de la Sota, A. Quijada-Freire, C. Mir, and D. López. 2021. Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry. Int.J.Mol.Sci. 22.
Lorente, E., M. Marcilla, P. G. de la Sota, A. Quijada-Freire, C. Mir, and D. López. 2021. Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry. Int.J.Mol.Sci. 22.
PUBMED DOIde la Sota, P. G., E. Lorente, L. Notario, C. Mir, O. Zaragoza, and D. López. 2021. Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus. Biomedicines. 9.
de la Sota, P. G., E. Lorente, L. Notario, C. Mir, O. Zaragoza, and D. López. 2021. Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus. Biomedicines. 9.
PUBMED DOIPredicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern.
Martín-Galiano, A. J., F. Diez-Fuertes, M. J. McConnell, and D. López. 2021. Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern. Front Immunol. 12:732693.
PUBMED DOIPrediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1.
López, D. 2022. Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1. Biomedicines. 10.
PUBMED DOIAbundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome.
Lorente, E., A. J. Martín-Galiano, D. M. Kadosh, A. Barriga, J. Garcia-Arriaza, C. Mir, M. Esteban, A. Admon, and D. López. 2022. Abundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome. J.Proteome.Res. 21:164-171.
DOICross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins
Tajuelo, A., M. López-Siles, V. Mas, P. Perez-Romero, J. M. Aguado, V. Briz, M. J. McConnell, A. J. Martín-Galiano, and D. López. 2022. Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Int.J.Mol.Sci. 23.
PUBMEDPredicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern.
López, D. 2022. Predicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern. Front Immunol. 13:832889.
PUBMEDGarcia-Arriaza, J., M. Esteban, and D. López. 2021
Garcia-Arriaza, J., M. Esteban, and D. López. 2021. Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus. Biomedicines. 9.
PUBMEDDiagnósitico microbiológico y control de la legionelosis
Pelaz Antolín, C., et al., En Procedimientos en Microbiología Clínica, E.C.y.R. Cantón, Editor. 2005, SEIMC. p. 1-72.
PUBMEDLegionella-Biofilms-Amebas, un problema industrial, de sanidad ambiental y de salud pública
Juana María González-Rubio, Celia Játiva, Almudena Cascajero, Fernando González-Camacho. Infoplagas, nº 112, agosto 2023 pags: 20-24. (Artículo de divulgación).
DOIPrograma de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores). Programas de Vigilancia Microbiológica pags: 74-80. Centro Nacional de Microbiología, Madrid: Instituto de Salud Carlos III, 2021.
Bellido B y Pelaez C: Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores). Programas de Vigilancia Microbiológica pags: 74-80. Centro Nacional de Microbiología, Madrid: Instituto de Salud Carlos III, 2021.
Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores) Programas de Vigilancia Microbiológica Centro Nacional de Microbiología.
Fernando González-Camacho y Almudena Cascajero. Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores) Programas de Vigilancia Microbiológica Centro Nacional de Microbiología. Volumen 2:77-89. 2021-2022 Majadahonda (Madrid); Instituto de Salud Carlos III, Centro Nacional de Microbiología: 2023.
Chikungunya virus infections among travellers returning to Spain, 2008 to 2014
3. Maria Dolores Fernandez Garcia; Mathieu Bangert; Fernando de Ory; Arantxa Potente; Lourdes Hernandez; Fatima Lasala; Laura Herrero; Francisca Molero; Anabel Negredo; Ana Vázquez; Teodora Minguito; Pilar Balfagón; Jesus de la Fuente; Sabino Puente; Eva Ramírez de Arellano; Mar Lago; Miguel Martinez; Joaquim Gascón; Francesca Norman; Rogelio Lopez Velez; Elena Sulleiro; Diana Pou; Nuria Serre; Ricardo Fernández Roblas; Antonio Tenorio; Leticia Franco; Maria Paz Sanchez Seco. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 21 - 36, (Sweden): 08/09/2016. ISSN 1560-7917
PUBMED DOILegionella feeleii: Ubiquitous Pathogen in the Environment and Causative Agent of Pneumonia
Vaccaro L, Gomes TS, Izquierdo F, Magnet A, Llorens Berzosa S, Ollero D, Salso S, Alhambra A, Gómez C, López Cano M, Pelaz C, Bellido Samaniego B, Del Aguila C, Fenoy S, Hurtado-Marcos C. Front Microbiol. 2021;12:707187.
DOIContent with Investigacion .
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Maribel Jiménez Alonso
Tenured Scientist
ORCID code: 0000-0002-5615-3087
Doctor in Pharmacy from the Complutense University of Madrid (1994) and Extraordinary Doctorate Award. She started her research activity at ISCIII in 1990 in the field of leishmaniasis. Currently, she is the head of the LEM where she develops her scientific work in the field of entomological surveillance of phlebotomine sandflies in the CM and other studies in the field of molecular biology, mainly applied to the model of Leishmania infantum and its vector Phlebotomus perniciosus. Member of the team of experts of the ISCIII that participates in the elaboration of Rapid Risk Assessments and in the working groups in charge of the elaboration of National Plans of Prevention, Surveillance and Control of Vector-borne Diseases of the CCAES, Ministry of Health. She is currently “Operational Focal Point” for vector-borne diseases at national level for the One Health-Vectornet network (EFSA and ECDC) and coordinator of the VectorNet-Spain network since July 2024. In addition, she is a member of the expert committee of the Network of Surveillance and Control of Vectors with public health interest in the Community of Madrid. In addition, she is part of a research group from CIBER (CIBERINFEC; CB21/13/00110).
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Inés Martín Martín
Tenured Scientist
ORCID code: 0000-0002-0956-7324
Within Medical Entomology, my work focuses on the study of phlebotomine sand flies and culicidae as vectors of leishmaniasis and arbovirosis, respectively. In 2014 I obtained my PhD degree “cum laude” with European mention from the Complutense University of Madrid. My PhD Thesis (developed at the Instituto de Salud Carlos III), focused on the study of phlebotomine sandfly saliva. Subsequently, during my postdoctoral period, I worked on insect gene editing, molecular, biochemical and functional characterization of insect saliva proteins and their role in the infection and transmission of pathogens. Most of my scientific career has been developed at the Laboratory of Malaria and Vector Research, National Institutes of Health (NIH), USA. Since 2021 I am a Senior Scientist at the Laboratory of Medical Entomology (ISCIII).
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Ricardo Molina Moreno
Doctor Ad Honorem
ORCID code: 0000-0001-6662-173X
Doctor in Biological Sciences from the Complutense University of Madrid (1994). In 1979 he began his professional career at the Instituto de Salud Carlos III (ISCIII), where he became a researcher in 1985. He was in charge of the Medical Entomology Laboratory from that year until his retirement in 2023. He is currently a doctor linked “Ad Honorem”. He has extensive experience in medical entomology, advising the Ministry of Health (CCAES) and Health Departments of Autonomous Communities, on surveillance and control of arthropods transmitting vector-borne diseases. In recent years he has been involved in surveillance programs in Spain for leishmaniasis vectors, especially in the Fuenlabrada outbreak, and for viruses causing Crimean-Congo hemorrhagic fever and dengue. Also in the surveillance of invasive exotic mosquitoes, especially Aedes albopictus, in ports and airports. In his last stage he has been part of the research group within the CIBER (CIBERINFEC; CB21/13/00110).
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Marcos López de Felipe Escudero
Predoctoral contract FPU
ORCID code: 0000-0002-2919-836X
Graduated in Biology from the Autonomous University of Madrid and Master in Tropical Parasitic Diseases from the University of Valencia. He started his professional career in 2019 in surveillance and management of hematophagous diptera of veterinary-medical interest, as well as other urban pests. In 2024 he began his work at the Instituto de Salud Carlos III (ISCIII) within the framework of the project “Evaluation of the anti-leishmanicidal effect of the bacterium Tc1 and its derivatives in the intravectorial cycle of the parasite” directed by Dr. Inés Martín Martín where he continues after the award of a FPU fellowship. He has extensive experience in medical entomology, especially in surveillance and vector control and taxonomic identification. Her career so far has focused mainly on the study of phlebotomine sand flies, simulids and culicidae, with special attention to citizen science.
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Eva Pérez Martínez
Clinical and Biomedical Laboratory Technician
ORCID code: 0000-0002-6553-9969
Graduated in 2019 from the Advanced Vocational Training Program in Clinical and Biomedical Laboratory Sciences. I began my professional career in 2020 at Eurofins Megalab laboratories. In 2024, I started working as a freelance professional on an international project focused on the bioecology of phlebotomine sand flies in urban environments across the Mediterranean Basin, conducting fieldwork in Spain, Italy, Greece, and southern France within the framework of citizen science. Since 2025, I have been part of the Medical Entomology Laboratory at the Instituto de Salud Carlos III (ISCIII), where I work as a laboratory technician on the project “Biochemical and functional characterization of salivary proteins from Phlebotomus perniciosus and their role in Leishmania infantum infection (PERNIPROT)”, led by Dr. Inés Martín Martín.
List of staff