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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
Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin
Garcia-Barreno B, Delgado T, Benito S, Casas I, Pozo F, Cuevas MT, et al. Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin. J Gen Virol. 2014;95(Pt 5):1033-42.
PUBMED DOIEpidemic history of hepatitis C virus genotypes and subtypes in Portugal.
Palladino C, Ezeonwumelu IJ, Marcelino R, Briz V, Moranguinho I, Serejo F, Velosa JF, Tato Marinho R, Borrego P, Taveira N. 2018. Epidemic history of hepatitis C virus genotypes and subtypes in Portugal. Sci Rep. 2018; 8:12266. (A; FI= 4.12; Q1 Multidisciplinary Sciences; DOI:10.1038/s41598-018-30528-0).
PUBMED DOILow frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study.
Palladino C, Sanchez-Carrillo M, Mate-Cano I, Vazquez-Morón S, Jiménez-Sousa MA, Gutiérrez-Rivas M, Resino S, Briz V. Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study. Sci Rep. 2017; 7(1):2892. (A; FI= 4.12; Q1 Multidisciplinary Sciences).
PUBMED DOIPlasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernández-Pato A; Virseda-Berdices A, Ryan P; Martínez-González O, Peréz-García F, Resino S, Martin-Vicente M, Valle-Millares D, Brochado-Kith O; Blancas R; Ceballos FC; Bartolome-Sánchez S; Vidal-Alcántara EJ; Alonso-Menchén D, Blanca-López N; Ramirez Martinez-Acitores I, Rava M, Jiménez-Sousa MA (‡ *), Amanda Fernández-Rodríguez (‡ *). Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Emerg Microbes Infect 2022; 11(1):676-688 (A; FI= 19.57; D1, Infectious Diseases; JCR 2021).
PUBMED DOIMild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study.
García-Broncano P, Medrano LM, Berenguer J, Brochado O, González-García J, Jiménez-Sousa MA, Quereda C, Sanz J, Téllez MJ, Díaz L, Jiménez JL, Muñoz-Fernández MA, Resino S (*). Mild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study. J Infect 2020; 80(1):99-110. (A; FI= 6.07; Q1, Infectious Diseases; JCR 2020).
PUBMED DOIEfficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease
Buitrago MJ, Aguado JM, Ballen A, Bernal-Martinez L, Prieto M, Garcia-Reyne A, Garcia-Rodriguez J, Rodriguez-Tudela JL, Cuenca-Estrella M. Efficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease. Clin Microbiol Infect. 2013 Jun;19(6):E271-7. doi: 10.1111/1469-0691.12110. Epub 2013 Mar 7. PMID: 23464751.
PUBMED DOIPotent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses
Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E. J Virol. 2022 Jan 12, 96(1): e0134321
PUBMED DOIHIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic
Cabrera-Rodríguez R, Hebmann V, Marfil S, Pernas M, Marrero-Hernández S, Cabrera C, Urrea V, Casado C, Olivares I, Márquez-Arce D, Pérez-Yanes S, Estévez-Herrera J, Clotet B, Espert L, López-Galíndez C, Biard-Piechaczyk M, Valenzuela-Fernández A, Blanco J. Sci Rep. 2019 Apr 3,9(1):5544
PUBMED DOIViral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera MS, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. mBio. 2018 Apr 10,9(2): e02338-17
PUBMED DOIViral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors.
Colomer-Lluch M, Kilpelainen A, Pernas M, Peña R, Ouchi D, Jimenez-Moyano E, Dalmau J, Casado C, López-Galíndez C, Clotet B, Martinez-Picado J, Prado JG. J Virol. 2022 Jan 12, 96(1): e0149921. doi: 10.1128/JVI.01499-21. Epub 2021 Oct 20.
PUBMED DOIContribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression
Valenzuela-Fernández A, Cabrera-Rodríguez R, Casado C, Pérez-Yanes S, Pernas M, García-Luis J, Marfil S, Olivares I, Estévez-Herrera J, Trujillo-González R, Blanco J, Lopez-Galindez C. Biomedicines. 2022 Sep 2,10(9):2172.
PUBMED DOIPrevalence of HIV-1 dual infection in LTNP-Elite Controllers
María Pernas, Concepción Casado, Virginia Sandonis, Carolina Arcones, Carmen Rodríguez , Ezequiel Ruiz-Mateos , Eva Ramírez de Arellano , Norma Rallón , Margarita Del Val , Eulalia Grau, Mariola López-Vazquez , Manuel Leal , Jorge del Romero , Cecilio López Galíndez . (2013). J.of AIDS. 64, 3, 225-231. IF 4.262
PUBMED DOIA Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Retroviral Control.
Istvan Bartha Jonathan M Carlson, Chanson J Brumme, Paul J McLaren, Zabrina L Brumme, Mina John, David W Haas, Javier Martinez-Picado, Cecilio López Galíndez, Andri Rauch, Huldrych F Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Jennifer Listgarten, Nico Pfeifer, Zoltan Kutalik, Todd M Allen, Viktor Müller, P Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay, for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study. (2013). Elife. 2013;2:e01123
PUBMED DOIFactors Leading to the Loss of Natural Elite Control of HIV-1 Infection
Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, León A, Rodriguez C, Benito JM, Rallón N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, García F, Alcamí J, Muñoz-Fernández M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. J Virol. 2018 Feb 12,92(5): e01805-17
PUBMED DOIContent with Investigacion .
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Óscar Zaragoza Hernández
Research Professor
ORCID code: 0000-0002-1581-0845
Dr. Oscar Zaragoza graduated in Biology from the Complutense University of Madrid in 1995 and obtained his PhD from the Autonomous University of Madrid. He completed his doctoral thesis (2000) at the CSIC under the direction of Dr. Juana María Gancedo on the topic of glucose catabolite repression in Saccharomyces cerevisiae. During this period, he was also tutored by Dr. Carlos Gancedo in collaborative projects, that allowed him to start working with the pathogenic yeast Candida albicans.
After a brief postdoctoral stay in the same laboratory, in 2001, he joined the laboratory of Dr. Arturo Casadevall (Albert Einstein College of Medicine, New York), where he specialized in research into virulence mechanisms of pathogenic fungi, mainly Cryptococcus neoformans. In 2006 he joined the National Center for Microbiology of the ISCIII thanks to a “Ramón y Cajal” contract and he became staff scientist in 2009. Currently, he occupies the rank of Research Professor of the OPIs.
During his career, he has published more than 140 articles, 4 book chapters and a popular book ("Microscopic fungi: Friends or Enemies?"). He has obtained public and private projects, and participates as CoIP of a CIBERINFEC group. He has supervised seven doctoral theses, and numerous master's thesis projects.
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Alba Torres Cano
PhD student (FPI contract)
ORCID code: 0009-0008-3151-1803
Alba Torres Cano has a degree in Health Biology from the University of Alcalá de Henares (UAH), and completed the master's degree "Microbiology Applied to Public Health and Infectious Diseases" from the UAH. He completed his master's thesis at the CNM under the direction of Dr. Zaragoza in 2022, focusing on pathogenic yeasts. In that year, he joined the ISCIII with an FPI predoctoral contract under the direction of Dr. Óscar Zaragoza.
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Alejandra Lora Plaza
PhD student (FPI contract)
ORCID code: 0009-0004-4344-1583
Alejandra Lora Plaza graduated in Health Biology and completed the Master in Applied Microbiology in Public Health and Infectious Diseases Research (2021) at the University of Alcalá in both cases. She joined the Department of Microbiology of the Faculty of Biology of the University of Barcelona to carry out her internship and her final degree work. Subsequently, she did her Master's thesis at the Microbiology Laboratory of the Hospital Universitario Príncipe de Asturias. In 2022 she joined the Public Health and Epidemiology group at the Marqués de Valdecilla Research Institute (IDIVAL), Santander, as a research support technician. In 2024 he joined Dr. Concha Gil's group in the Department of Microbiology and Parasitology at the Faculty of Pharmacy of the Complutense University of Madrid focusing on yeasts.
In 2025 she joined ISCIII with a predoctoral FPI fellowship under the direction of Dr. Óscar Zaragoza.
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