Molecular Genetics of Urogenital Pathologies: Male Infertility and Prostate Cancer. IP: Sara Larriba. This line of research is focused on the understanding of the genetic and epigenetic mechanisms involved in male urogenital disorders. Specifically, one of our projects deals with the analysis of the transcriptome and the tissue gene expression regulation mechanisms in disease. This study is complemented with the identification of new non invasive genetic biomarkers useful for the diagnosis and prognosis of urogenital pathologies.

Molecular bases of the Hereditary diseases: Cistinuria, Diseases associated with mutations in amino acid transporters, Megalencephalic Leukoencephalopathy with subcortical cysts (MLC) and Wolfram syndrome. IP: Virginia Nunes. This research line is focused on: i) the understanding of the renal amino acid reabsortion, ii) the identification of new diseases associated with alterations in the amino acids transport (deafness and cataracts), iii) the determination of new genetic factors that help to establish the molecular bases of the mentioned diseases and searching for possible therapeutical strategies, using knockout mice models as a tool. 

Miology. IP: Montse Olivé. This research line is focused on the study of rare muscular diseases specially myopathies with protein aggregates, but also other structural myopathies, by using clinical, morphological and genetic approaches. Our aim is to identify the molecular basis of new muscle disorders and to define their clinical and muscle biopsy features.

Cancer and immune response: Development of new immunosupressors and therapeutic antitumoral agents. IP: Mercè Pérez. This line of research is focused on determining the functional and therapeutic effect of the RCAN proteins in the tumor progression and metastasis in triple negative breast cancer. On the other hand, our group identified 6 hits, small non-peptide molecules that mimic the functional effect of RCANs, which are being improved to obtain leads that will be assessed in vivo to determine their immunosuppressive and anti tumour therapeutic efficacy.

1st ENMC European meeting: The EURO-NMD pathology working group Recommended Standards for Muscle Pathology Amsterdam, The Netherlands, 7 December 2018

Udd B, Stenzel W, Oldfors A, Olivé M, Romero N, Lammens M, Kusters B, Sewry C, Goebel H, Evangelista T

2019

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Alonso-Jimenez A, Kroon RHMJM, Alejaldre-Monforte A, Nuñez-Peralta C, Horlings CGC, van Engelen BGM, Olivé M, González L, Verges-Gil E, Paradas C, Márquez C, Garibaldi M, Gallano P, Rodriguez MJ, Gonzalez-Quereda L, Dominguez Gonzalez C, Vissing J, Fornander F, Eisum AV, García-Sobrino T, Pardo J, García-Figueiras R, Muelas N, Vilchez JJ, Kapetanovic S, Tasca G, Monforte M, Ricci E, Gomez MT, Bevilacqua JA, Diaz-Jara J, Zamorano II, Carlier RY, Laforet P, Pelayo-Negro A, Ramos-Fransi A, Martínez A, Marini-Bettolo C, Straub V, Gutiérrez G, Stojkovic T, Martín MA, Morís G, Fernández-Torrón R, Lopez De Munaín A, Cortes-Vicente E, Querol L, Rojas-García R, Illa I, Diaz-Manera J

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. (ISSN/ISBN: 00223050).

2019

Cis-trans proline isomers in the catalytic domain of calcineurin

Teixeira J., Guasch A., Biçer A., Aranguren-Ibáñez Á., Chashmniam S., Paniagua J., Pérez-Riba M., Fita I., Pons M.

FEBS JOURNAL. (ISSN/ISBN: 17424658).

2019

Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions

Olive, Montse; Engvall, Martin; Ravenscroft, Gianina; Cabrera-Serrano, Macarena; Jiao, Hong; Bortolotti, Carlo Augusto; Pignataro, Marcello; Lambrughi, Matteo; Jiang, Haibo; Forrest, Alistair R. R.; Benseny-Cases, Nuria; Hofbauer, Stefan; Obinger, Christian; Battistuzzi, Gianantonio; Bellei, Marzia; Borsari, Marco; Di Rocco, Giulia; Viola, Helena M.; Hoo, Livia C.; Cladera, Josep; Lagerstedt-Robinson, Kristina; Xiang, Fengqing; Wredenberg, Anna; Miralles, Francesc; Jose Baiges, Juan; Malfatti, Edoardo; Romero, Norma B.; Streichenberger, Nathalie; Via, Christophe; Claeys, Kristl G.; Straathof, Chiara S. M.; Goris, An; Freyer, Christoph; Lammens, Martin; Bassez, Guillaume; Kere, Juha; Clemente, Paula; Sejersen, Thomas; Udd, Bjarne; Vidal, Noemi; Ferrer, Isidre; Edstrom, Lars; Wedell, Anna; Laing, Nigel G.;

NATURE COMMUNICATIONS. (ISSN/ISBN: 20411723). 10(1396):

2019

Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations

Savarese M, Palmio J, Poza J, Weinberg J, Olive M, Cobo A, Vihola A, Jonson P, Sarparanta J, García-Bragado F, Urtizberea J, Hackman P, Udd B

ANNALS OF NEUROLOGY. (ISSN/ISBN: 03645134).

2019

Late-onset thymidine kinase 2 deficiency: a review of 18 cases

Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, Fuiza-Luces C, García García J, Morís G, Olivé M, Miralles F, Díaz-Manera J, Caballero C, Méndez-Ferrer B, Martí R, García Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MÁ, Paradas C

2019

Late onset distal myopathy: A new telethoninopathy

Blanco-Palmero VA, Hernández-Laín A, Uriarte-Pérez de Urabayen D, Cantero-Montenegro D, Olivé M, Domínguez-González C

NEUROMUSCULAR DISORDERS. (ISSN/ISBN: 09608966). 29(1): 80-83

2019

Different mitochondrial genetic defects exhibit the same protein signature of metabolism in skeletal muscle of PEO and MELAS patients: A role for oxidative stress

Santacatterina F., Torresano L., Núñez-Salgado A., Esparza-Molto P., Olive M., Gallardo E., García-Arumi E., Blazquez A., González-Quintana A., Martín M., Cuezva J.

FREE RADICAL BIOLOGY AND MEDICINE. (ISSN/ISBN: 08915849). 126235-248

2018

Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member

Dahl-Halvarsson M., Olive M., Pokrzywa M., Ejeskär K., Palmer R., Uv A., Tajsharghi H.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. (ISSN/ISBN: 00278424). 115(28): E6566-E6575

2018

Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in Age-Related Hearing Loss.

Espino Guarch M, Font-Llitjós M, Murillo-Cuesta S, Errasti-Murugarren E, Celaya AM, Girotto G, Vuckovic D, Mezzavilla M, Vilches C, Bodoy S, Sahún I, González L, Prat E, Zorzano A, Dierssen M, Varela-Nieto I, Gasparini P, Palacín M, Nunes V

ELIFE (ISSN/ISBN: 2050084X). 7 : ARTN E31511

2018

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Cistinuria: Identificación y caracterización de nuevos genes y moduladores de la litiasis de cistina como dianas terapeúticas

Nunes Martinez, Virginia (Investigador principal (IP))

Ref.: PI16/00267

Entitat finançadora:
  • FIS-INSTITUTO DE SALUD CARLOS III

2017-01-01 - 2019-12-31

Impacto de la pérdida de función en un transportador SLC7 de aminoácidos en sordera y fragilidad muscular. Estudio en pacientes y en un modelo experimental en ratón.

Nunes Martinez, Virginia (Investigador principal (IP))

Ref.: ER17P2AC730

Entitat finançadora:
  • ACCI 20016

2017-01-01 - 2017-12-31

FIRST SPECIFIC NON-PEPTIDE INHIBITORS OF THE CALCINEURIN – NFATc SIGNALLING PATHWAY

Perez Riba, Merce (Investigador principal (IP))

Ref.: 2017-02-005-CANINHIB

Entitat finançadora:
  • FUND.INST.CENTRES RECER.CATALALUYA

2017-01-01 - 2017-12-31

IDENTIFICACION Y CARACTERIZACIÓN DE NUEVOS GENES Y MODULADORES DE LA LITIASIS DE CISTINA COMO DIANAS TERAPÉUTICAS

Nunes Martinez, Virginia (Investigador principal (IP))

Ref.: U730AjutsCIBERERiniciotesisdoctorales

Entitat finançadora:
  • FIS-INSTITUTO DE SALUD CARLOS III

2016-09-01 - 2017-08-31

Identificación de nuevos factores pronóstico y diagnóstico de patologías urogenitales basados en microRNAs en plasma seminal

Mata Vila, Ana (Participante); Castells Esteve, Manel (Participante); BASSAS ARNAU, Lluís (Participante); VIGUÉS JULIÀ, FRANCESC (Participante); Larriba Bartolome, Sara (Investigador principal (IP))

Ref.: PI15/00153

Entitat finançadora:
  • INSTITUTO DE SALUD CARLOS III

2016-01-01 - 2019-12-31

A precise approach for nucleoside-based therapy of neuromuscular disorders with defects in mitochondrial DNA.

Olivé Plana, Montserrat (Investigador principal (IP))

Ref.: PMP15/00025

2016-01-01 - 2019-12-31

ANÁLOGOS NO PEPTÍDICOS DEL PÉPTIDO R3 COMO HERRAMIENTA PARA INHIBIR EL CRECIMIENTO TUMORAL DEL TNBC MEDIANTE BLOQUEO DE LA ANGIOGÉNESIS Y DEL RECLUTAMIENTO DE NEUTRÓFILOS

Perez Riba, Merce (Investigador principal (IP))

Ref.: SAF2015-66365-R

Entitat finançadora:
  • MINISTERIO DE EDUCACIÓN Y CIENCIA

2016-01-01 - 2018-12-31

Caracterización de una nueva forma de miopatía vacuolar autofágica con depósito lisosomal de pigmento

Olivé Plana, Montserrat (Investigador principal (IP))

Ref.: PR331/14

Entitat finançadora:
  • FUNDACIÓN GENZYME

2015-03-30 - 2017-01-31

Análisis genómico y funcional de infertilidades hereditarias humanas.

Larriba Bartolome, Sara (Participante)

2015-01-01 - 2015-12-31

Implicación de L-ergothioneína en la litiasis renal de cistina: posible aplicación terapéutica para cistinuria

Nunes Martinez, Virginia (Investigador principal (IP)); Prat Pedrola, Ester (Participante); López de Heredia Alonso, Miguel (Investigador/a)

Ref.: PI13/00121

Entitat finançadora:
  • INSTITUTO DE SALUD CARLOS III

2014-01-01 - 2016-12-25

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Molecular basis of the amino acid transport in kidney and skeletal muscle: Lessons from knockout mouse models.

Nunes Martinez, Virginia (Director) Doctorando: Clara Vilches Caubet

2016

Mecanismes moleculars i efecte terapèutic antiangiogènic del pèptid R3178-210 en un model ortotòpic de càncer de mama

Perez Riba, Merce (Director) Doctorando: Sònia Solé Sánchez

2015

New Insights in the Endogenous Regulation of the Calcineurin-NFATc Pathway by RCAN Proteins and Identification of Novel Non-Peptidic Calcineurin Inhibitors

Perez Riba, Merce (Director) Doctorando: Álvaro Aranguren Ibáñez

2015

Bases Moleculars de la Leucoencefalopatia megalencefàlica amb quists subcortical. Utilització de models animals i cel.lulars.

Estevez Povedano, Raul (Codirector) Doctorando: Sònia Sirisi Dolcet; Nunes Martinez, Virginia (Codirector) Doctorando: Sònia Sirisi Dolcet

2014

Phylogenomic Analysis and Genomic Structure of Human (Regulators of Calcineurin (RCAN) Genes. Effect of RCAN Overexpression on Lymphocyte Development and Function

Perez Riba, Merce (Director) Doctorando: Serrano Candelas, Eva

2012

Mouse models of HATs: cystinuria and LAT2 protein

Manuel Palacin (Director) Doctorando: Meritxell Espino Guarch; Nunes Martinez, Virginia (Director) Doctorando: Meritxell Espino Guarch

2012

Unraveling the molecular mechanisms involved in RCAN-peptide mediated inhibition of calcineurin-NFAT signaling and its potential as an inhibitor of tumor progressions

Perez Riba, Merce (Director) Doctorando: Sergio Martínez Hoyer

2012

Mouse models of HATs: cystinuria and LAT2 protein

Nunes Martinez, Virginia (Director) Doctorando: Mertixell Espino Guarch

2012

Avenços en la fisiopatologia de la Leucoencefalopatia Megalencefàlica ajb quists subcorticals.

Nunes Martinez, Virginia (Director) Doctorando: Anna Duarri Piqué; Estevez Povedano, Raul (Director) Doctorando: Anna Duarri Piqué

2010

Caracterización Molecular y Fenotípica del Síndrome de Wolfram Mediante el Análisis del Gen WFS1 y del DNA Mitocondrial

Nunes Martinez, Virginia (Director) Doctorando: Enric Domènech Estévez

2005

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Methods and markers for azoospermia characterization (EP18382194.1)

BASSAS ARNAU, Lluís (Autor o Coautor); Larriba Bartolome, Sara (Autor o Coautor)

REAGENTS AND METHODS FOR THE TREATMENT OF DISEASES BASED ON THE INHIBITION OF CALCINEURIN - NFAT SIGNALLING PATHWAY

Perez-Riba, Merce (Inventores-as/autores-as/obtentores-as); MARTÍNEZ HØYER, Sergio (Inventores-as/autores-as/obtentores-as); MESSEGUER PEYPOCH, Ramon (Inventores-as/autores-as/obtentores-as); ITARTE FRESQUET, Emilio (Inventores-as/autores-as/obtentores-as)

MÉTODO IN VITRO PARA PREDECIR LA FECUNDIDAD DEL SEMEN

Larriba Bartolome, Sara (Inventores-as/autores-as/obtentores-as); BASSAS ARNAU, Lluís (Inventores-as/autores-as/obtentores-as)

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The group has:

  • Identified and characterised the genes responsible for:
    • Cystinuria (SLC3A1 and SLC7A9).
    • Lysinuric protein intolerance (LPI) (SLC7A7).
    • Megalencephalic leukoencephalopathy with subcortical cysts (MLC1) (GlialCAM).
    • Muscular diseases.
  • Generated knockout mouse models for cystinuria and MLC1.
  • Contributed to describing clinical and pathological phenotypes for myofibrillar myopathies and also for protein aggregate myopathies.
  • Reported new myological entities.
  • Established a genotype/phenotype correlation for Wolfram syndrome based on the expected effect of the mutations on protein expression and the first rate of disease progression.
  • Participated as a member of the EURO-WABB project in the European Registry for Wolfram, Alström and Bardet-Biedl syndromes, as well as in their clinical guidelines.
  • Contributed to the molecular characterisation of spermatogenic disorders (identifying sequencing variants associated with infertility, determining the gene-expression profile of the tissue and studying the mechanisms of transcriptional and post-translational regulation).
  • Contributed to the molecular characterisation of endogenous inhibitors of the calcineurin-NFATc signalling pathway in human T cells: the physiological relevance of RCAN proteins and their therapeutic potential. Development of non-peptide molecules which imitate the physiological role of RCAN.

 

 

Proyectos financiados por el Instituto de Salud Carlos III (ISCIII) y cofinanciados por el Fondo Europeo de Desarrollo Regional (FEDER):

 

Identificación de nuevos factores pronóstico y diagnóstico de patologías urogenitales basados en microRNAs en plasma seminal

PI15/00905. 01/2016-12/2018. 81.500 €. IP: Sara Larriba Bartolomé.

Profundizar en el estudio de los niveles de expresión de miRNAs extracelular en semen y evaluar su utilización como biomarcador no invasivo en patologías urogenitales. La concentración de ciertos miRNAs (de manera individual y combinada) son capaces de discernir muestras con tumor y sin tumor con una especifidad y sensibilidad suficiente para el diseño de un test con utilidad diagnóstica.