Human Molecular Genetics

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.

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: 2041-1723) 2019

Semen miRNAs Contained in Exosomes as Non-Invasive Biomarkers for Prostate Cancer Diagnosis

Barceló M., Castells M., Bassas L., Vigués F., Larriba S.

SCIENTIFIC REPORTS (ISSN: 2045-2322) 2019

Cylindrical spirals in two families: Clinical and genetic investigations

Beecroft S, Olive M, Quereda L, Gallano M, Ojanguren I, McLean C, McCombe P, Laing N, Ravenscroft G

NEUROMUSCULAR DISORDERS (ISSN: 0960-8966 ) 2020

ASC-1 Is a Cell Cycle Regulator Associated with Severe and Mild Forms of Myopathy

Villar-Quiles R, Catervi F, Cabet E, Juntas-Morales R, Genetti C, Gidaro T, Koparir A, Yüksel A, Coppens S, Deconinck N, Pierce-Hoffman E, Lornage X, Durigneux J, Laporte J, Rendu J, Romero N, Beggs A, Servais L, Cossée M, Olivé M, Böhm J, Duband-Goulet I, Ferreiro A

ANNALS OF NEUROLOGY (ISSN: 0364-5134) 2020

Actininopathy: Mutations in the J domain of DNAJB6 cause dominant distal myopathy

Palmio J, Jonson P, Inoue M, Sarparanta J, Bengoechea R, Savarese M, Vihola A, Jokela M, Nakagawa M, Noguchi S, Olivé M, Masingue M, Kerty E, Hackman P, Weihl C, Nishino I, Udd B

NEUROMUSCULAR DISORDERS (ISSN: 0960-8966) 2020

Los miRNAs exosomales en semen como biomarcadores de la presencia de espermatozoides en tejido testicular. Desarrollo y optimización de un método diagnóstico

Larriba Bartolome, Sara ( Principal investigator (PI))

Funder:

• FIS-Instituto de Salud Carlos III

01/01/2019 - 31/12/2020

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

Nunes Martinez, Virginia ( Principal investigator (PI))

Funder:

• FIS-Instituto de Salud Carlos III

01/01/2016 - 30/11/2020

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

Larriba Bartolome, Sara ( Principal investigator (PI))

Funder:

• FIS-Instituto de Salud Carlos III

01/01/2016 - 30/11/2020

Impacto de las técnicas de secuenciación masiva para el diagnóstico molecular en una serie de pacientes con miopatía sin diagnóstico genético

Olive Plana, Montserrat ( Principal investigator (PI))

Funder:

• FIS-Instituto de Salud Carlos III

01/01/2015 - 30/06/2019

In vitro method for predicting fecundity of semen
PCT number: PCT/ES2012/070268.
INVENTORS: Sara Larriba, Lluís Bassas.
OWNER ENTITIES: IDIBELL/Fundació Puigvert
VALIDATED COUNTRIES: EU (Germany, France, United Kingdom, Italy, Spain, Portugal, Belgium, Denmark, Sweden, Netherlands and Switzerland), y Canadá

Methods and markers for azoospermia characterization.

PCT number: PCT/EP2019/057079
INVENTORS: Sara Larriba, Lluís Bassas.
OWNER ENTITY: IDIBELL/Fundació Puigvert

Seminal miRNAs as non-invasive biomarkers for the diagnosis and/or prognosis of prostate cancer España.

INVENTORS: Manel Castells Esteve; Francesc Vigués Juliá; Sara Larriba Bartolomé.
OWNER ENTITY: INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE (IDIBELL).

ERGOTHIONEINE, S-METHYL-ERGOTHIONEINE, AND USES THEREOF

INVENTORS: Virginia Nunes, Miguel López de Heredia
OWNER ENTITY: INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE (IDIBELL), CIBER, UNIVERSITAT DE BARCELONA

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.