Human Molecular Genetics

Summary

The main aim of the Human Molecular Genetics group is to better understand the genetic and molecular bases of the hereditary monogenic or complex diseases and/or the immunoinflammatory processes using high throughput strategies, such as genomics, transcriptomics, proteomics as well as functional and structural approaches to characterize clinical and pathological features of rare disorders. Additionally, we aim to develop new molecular/cellular therapies. We have specific formation in Human Genetics, Biochemistry, Molecular and Cellular Biology related to Biomedicine field. The multidisciplinarity of the group allows us to enrich the experimental focus of our research projects.

419 Publications

Strategic lines

Molecular Genetics of Urogenital Diseases. 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: Cystinuria, 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.

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.

Structure and physiopathology of SLC transporters: IP: Ekaitz Errasti Murugarren. This research line is focused on the understanding of Solute carrier (SLC) transporters, from a pathophysiological, functional and structural point of view. Particularly, amino acid transporters (SLC7 family) and choline-like transporters (SLC44 family) are of particular interest as potential therapeutic targets due to their association with neurodevelopmental and sensorineural disorders.

Selected Publications

Rullo Tubau J, Bartoccioni P, Llorca O, Errasti Murugarren E, Palacin M. HATs meet structural biology. Curr. Opin. Struct. Biol. 2022;74doi:10.1016/j.sbi.2022.102389.

Sánchez Morales A, Biçer A, Panagiotopoulos V, Crecente Garcia S, Benaiges C, Bayod S, Luís Hernández J, Busqué F, Matsoukas MT, Pérez Riba M, Alibés R. Design and synthesis of a novel non peptide CN-NFATc signaling inhibitor for tumor suppression in triple negative breast cancer. Eur. J. Med. Chem. 2022;238114514-114514. doi:10.1016/j.ejmech.2022.114514.

López Rodrigo O, Bossini Castillo L, Carmona FD, Bassas L, Larriba S. Genome-wide compound heterozygote analysis highlights DPY19L2 alleles in a non-consanguineous Spanish family with total globozoospermia. Reprod. Biomed. Online. 2022;45(2):332-340. doi:10.1016/j.rbmo.2022.03.035.

Plata Pena L, Lopez Rodrigo O, Bassas L, Larriba S. Experimental validation of seminal miR-31-5p as biomarker for azoospermia and evaluation of the effect of preanalytical variables. Andrology. 2022;doi:10.1111/andr.13286.

Cerván Martín M, Tüttelmann F, Lopes AM, Bossini Castillo L, Rivera Egea R, Garrido N, Lujan S, Romeu G, Santos Ribeiro S, Castilla JA, Carmen Gonzalvo M, Clavero A, Maldonado V, Vicente FJ, González Muñoz S, Guzmán Jiménez A, Burgos M, Jiménez R, Pacheco A, González C, Gómez S, Amorós D, Aguilar J, Quintana F, Calhaz Jorge C, Aguiar A, Nunes J, Sousa S, Pereira I, Pinto MG, Correia S, Sánchez Curbelo J, López Rodrigo O, Martín J, Pereira Caetano I, Marques PI, Carvalho F, Barros A, Gromoll J, Bassas L, Seixas S, Gonçalves J, Larriba S, Kliesch S, Palomino Morales RJ, Carmona FD. Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility. Commun. Biol. 2022;5(1):1220-1220. doi:10.1038/s42003-022-04192-0.

Selected Projects

21FIS034. Cistinuria: Validación de un nuevo biomarcador de litiasis de cistina en pacientes y diseño de un nuevo tratamiento, basados en moduladores de la litiasis de cistina identificados en modelos de ratón. Instituto de Salud Carlos III (ISCIII). Budget: 244420. 2021-2023. PI: NUNES MARTINEZ, VIRGINIA.

21MAR004. Therapeutical strategies for cystinuria. Fundació La Marató de TV3 . Budget: 200000. 2021-2024. PI: NUNES MARTINEZ, VIRGINIA.

20PNJ075. Role of HAT transporter on ILC2 and type II inflammation during obesity and insulin resistance. SIDRA MEDICINE. Budget: 13164. 2020-2023. PI: NUNES MARTÍNEZ, VIRGINIA.

Technology transfer

PAT074-Ergothioneine, s-methyl-ergothioneine and uses thereof
IP: Virginia Nunes
OWNERSHIP: 25% IDIBELL 25% UB 50%CIBERER
Applicant: FUNDACIÓ INSTITUT D'INVESTIGACIÓ BIOMÈDICA DE BELLVITGE (IDIBELL); UNIVERSITAT DE BARCELONA; CONSORCIO CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED, M.P.

License: Urine biomarker and reprofiling drug for cystinuria treatment and/or relief
PI: Dra. Virginia Nunes

More Information

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.