We protect your health through science
Investigation
Organ Transplant
Research Lines
Content with Investigacion .
Neisseria, Listeria y Bordetella
• Invasive Meningococcal Disease.
o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.
o Study and characterization of antimicrobial resistance mechanisms.
o Study and evaluation of conventional (polysaccharide) and new-generation (protein) vaccines.
• Gonococcal Infection (Gonorrhea).
o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.
o Study and characterization of antimicrobial resistance mechanisms.
• Listeriosis.
o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.
• Pertussis.
o Development and application of molecular techniques for the diagnosis and characterization of Bordetella pertussis, B. parapertussis, B. holmessi, and B. bronchiseptica.
Research projects
Content with Investigacion .
1. Project Title: Determination of the degree of identity of common antigens of N. meningitidis and N. gonorrhoeae using genomic and immunological tools.
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII. Program: Strategic Action in Intramural Health
Reference: PI23CIII/00040
Period: 2024-2026
Amount Awarded: €68,500
2. Project Title: Meningococcal Disease and Molecular Epidemiology (MEMORY).
Principal Investigator: Raquel Abad Torreblanca and Julio A. Vázquez Moreno
Funding Entity: Pfizer Inc.
Reference: MVP 352/21
Period: 2022-2024
Amount Awarded: €82,834.50
3. Project Title: Modelling Approaches to Guide Intelligent Surveillance for the Sustainable Introduction of Novel Antibiotics. MAGIcIAN.
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / International Joint Action / Joint Programming Initiatives (JPI) Program
Reference: AC19CIII/00002
Period: 2020-2024
Amount Awarded: €46,000
4. Project Title: Epidemiological, Microbiological, and Clinical Analysis of the Listeriosis Outbreak in Andalusia. LISMOAN Study.
Principal Investigator: José Miguel Cisneros Herreros
Funding Entity: FISEVI (Andalusian Public Foundation for Health Research Management)/FPS2020 Call for Proposals
Reference: PI-0001-2020
Period: 2020-2023
Amount Awarded: €114,954
5. Project Title: Population Structure of Neisseria meningitidis Using Massive Sequencing: A Potential Tool for Estimating Vaccine Effectiveness?
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / Strategic Action in Intramural Health
Reference: PI19CIII/00030
Period: 2020-2023
Amount Awarded: €67,153
6. Project Title: Management agreement between the Ministry of Health, Social Services and Equality (Directorate General of Public Health, Quality and Innovation) and the Carlos III Health Institute, for the laboratory determinations corresponding to the 2nd seroprevalence study in Spain.
Principal Investigator: Fernando de Ory and Julio A. Vázquez
Funding Entity: Directorate General of Public Health, Ministry of Health
Reference: MEG151/17
Period: 2018-2020
Amount Awarded: €565,663
7. Project Title: Effectiveness of the Meningococcal B Vaccine in Immunocompromised Children with Sickle Cell Disease
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: Spanish Society of Pediatric Hematology and Oncology Foundation (SEHOP)
Reference: MVP 199/18
Period: 2018-2020
Amount Awarded: €18,285
8. Project Title: Application of Massive Sequencing and Immunological Approaches in the Expression Analysis of New Vaccine Antigens in Meningococcal Populations
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / Strategic Action in Intramural Health
Reference: PI16CIII/00023
Period: 2017-2020
Amount Awarded: €115,084
9. Project Title: fHbp variability over time and potential coverage of the new meningococcal serogroup B vaccine (bivalent rLP2086/fHbp) in Spain.
Principal Investigators: Raquel Abad and Julio A. Vázquez
Funding Entity: Pfizer SLU
Reference: MVP 1273/16
Period: 2017-2020
Amount Awarded: €125,350
10. Project Title: Estimation of protection of a conjugate vaccine against meningococcus serogroup C based on a mathematical model.
Principal Investigator: Julio A. Vázquez and Javier Díez
Funding Entity: Higher Center for Research in Public Health (CSISP)
Reference: MVP 1116/11
Period: 2011-2017
Amount awarded: €143,750
Publications
HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients
Brochado-Kith; Martínez I; Berenguer J; et al; Fernández-Rodríguez A (AC); Resino S. (11/12). 2021. HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients. Journal of Biomedical Sciences. Springer Nature. 28-1.
DOIOLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest.
Pérez-García F; Resino S; Gómez-Sánchez E; et al; Jiménez-Sousa MÁ (10/10). OLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest. 2021. 51(4):e13416. doi: 10.1111/eci.13416.
Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb
Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb;50(2):453-60. doi: 10.1128/AAC.50.2.453-460.2006. PMID: 16436696; PMCID: PMC1366924.
PUBMED14. Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr
Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr;52(4):1244-51. doi: 10.1128/AAC.00942-07. Epub 2008 Jan 22. PMID: 18212093; PMCID: PMC2292508.
PUBMED DOIAlcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct
Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct;53(10):4514-7. doi: 10.1128/AAC.00585-09. Epub 2009 Jul 27. PMID: 19635955; PMCID: PMC2764190.
PUBMED DOIAlcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr
Alcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr;49(3):276-84. doi: 10.3109/13693786.2010.512926. Epub 2010 Sep 10. PMID: 20831364.
PUBMED DOIAlcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov
Alcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov;38(5):426-34. doi: 10.1016/j.ijantimicag.2011.06.005. Epub 2011 Aug 25. PMID: 21871783.
PUBMED DOIAlcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.
Alcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance. Front Microbiol. 2013 Jan 10;3:439. doi: 10.3389/fmicb.2012.00439. PMID: 23335918; PMCID: PMC3541703.
PUBMED DOIBernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24
Bernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24;63(6):e02399-18. doi: 10.1128/AAC.02399-18. PMID: 30910893; PMCID:PMC6535561.
PUBMED DOILupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23
Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23;88(4):e00882-19. doi: 10.1128/IAI.00882-19. PMID: 31964743; PMCID: PMC7093133.
PUBMED DOIAre Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane).
Ceballos FC; Ryan P; Blancas R; et al; Jiménez-Sousa MÁ (20/20). Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane). 2021; 8:718053. PMID: 34660629. doi: 10.3389/fmed.2021.718053.
T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA; Jiménez JL; Bellón JM; et al (1/10). CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study. J Acquir Immune Defic Syndr 2020 ;85(5):659-664. doi: 10.1097/QAI.0000000000002485.
PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients
Salguero, Sergio; Brochado-Kith, Oscar; Verdices, Ana Virseda; et al; Jiménez-Sousa María A (‡, AC); Resino, Salvador (‡, AC). (12/12). 2023. PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomedicine & pharmacotherapy. 159, pp.114220. ISSN 1950-6007.
Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology.
Virseda-Berdices, Ana; Concostrina-Martinez, Leyre; Martinez-Gonzalez, Oscar; et al; Fernandez-Rodriguez, Amanda (‡), Jiménez-Sousa María A (‡). (14/14). 2023. Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology. 95-1, pp.e28368. ISSN 1096-9071.
Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernandez-Pato, Asier; Virseda-Berdices, Ana; Resino, Salvador; et al; Jiménez-Sousa María A (‡, AC); Fernandez-Rodriguez, Amanda (‡). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. EMERGING MICROBES & INFECTIONS. 11(1):676-688. doi: 10.1080/22221751.2022.2038021.
Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy.
Virseda-Berdices, Ana; Brochado-Kith, Oscar; Diez, Cristina; et al; Jimenez-Sousa, Maria Angeles. (16/16). 2021. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy. 77(3):719-726. doi: 10.1093/jac/dkab444. ISSN 1460-2091.
Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1
Barac A, Kosmidis C, Alastruey-Izquierdo A, Salzer HJF; CPAnet. Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1;57(Supplement_2):S104-S109. doi: 10.1093/mmy/myy070. PMID: 30816975.
PUBMED DOILaursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun
Laursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun 29;6(3):E96. doi: 10.3390/jof6030096. PMID: 32610566.
PUBMED DOIProject 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 Jun
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, Vicente Anza D, Viñuelas J, Zapico MS, Cuenca-Estrella M; members of 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 Jun 25. doi: 10.1128/AAC.00358-18. PMID: 29941643.
PUBMED DOIIn vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1
Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1;74(5):1295-1299. doi: 10.1093/jac/dkz022. PMID: 30753499.
PUBMED DOIAdditional Information
Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored.
Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ.
Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).
Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored.
Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ.
Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).