Research Group on Human Translational Genomics

Metabolism and Organic Damage Area

Medium-term scientific research aims are to investigate mechanisms of pathogenesis and candidate therapies in Myotonic Dystrophy, Spinal Muscular Atrophy, LGMDD2, and cancer-induced cachexia; to optimize oligonucleotide drug delivery methods; and to screen and repurpose drugs in additional biomedical models in Drosophila
Coordinator
Dr. Rubén D Artero Allepuz
ruben.artero@uv.es

RESEARCHERS
Leading, R4

Rubén D Artero Allepuz    
Manuel Pérez Alonso

Established, R3

Arturo López Castel

Recognised/Emerging, R2

Dulce Peris Moreno
Javier Poyatos García
María Sabater Arcis
Natalia Galindo Riera
Raquel Atienzar Aroca
Xiomara Gislen Fernández Garibay

First Stage, R1

Anna Colom Rodrigo
Irene González Martínez
Natalia Mariel Riedel Bistoco
Nerea Moreno Cervera
Rosy Morejón Estévez

STAFF
Collaborating Researchers
Nurse
Technicians

Alicia Novella Estellés
Anna Ballestar Carrión
Iván Gimeno Martínez

Administrative assistant
Publications
BlockmiR AONs as site-specific therapeutic mbnl modulation in myotonic dystrophy 2D and 3D muscle cells and HSALR mice. Overby S, Cerro-Herreros E, Espinosa-Espinosa J, Gonzalez-Martinez I, Moreno N, Fernandez-Costa J, Balaguer-Trias J, Ramon-Azcon J, Perez-Alonso M, Moller T, Llamusi B, Artero R. Pharmaceutics. 2023 Mar 31;15(4):1118. doi: 10.3390/pharmaceutics15041118. PMID: 37111604

CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2. Poyatos Garcia J, Blazquez Bernal A, Selva Gimenez M, Bargiela A, Espinosa Espinosa J, Vazquez Manrique RP, Bigot A, Artero R, Vilchez JJ. Molecular Therapy. Nucleic Acids. 2023 Jan 11;31:324-338. doi: 10.1016/j.omtn.2023.01.004. PMID: 36789274

Development of potent tripodal G-quadruplex DNA binders and their efficient delivery to cancer cells by aptamer functionalised liposomes. Pont I, Galiana-Rosello C, Sabater-Arcis M, Bargiela A, Frias J, Albelda M, Gonzalez-Garcia J, Garcia-Espana E. Organic & Biomolecular Chemistry. 2023 Feb 1;21(5):1000-1007. doi: 10.1039/d2ob01911f. PMID: 36541358

Msi2 enhances muscle dysfunction in a myotonic dystrophy type 1 mouse model. Sabater-Arcis M, Moreno N, Sevilla T, Perez Alonso M, Bargiela A, Artero R. Biomedical Journal. 2023 Oct 3:100667. doi: 10.1016/j.bj.2023.100667. PMID: 37797921

Natural compound boldine lessens myotonic dystrophy type 1 phenotypes in DM1 drosophila models, patient-derived cell lines, and HSALR mice. Alvarez-Abril M, Garcia-Alcover I, Colonques-Bellmunt J, Garijo R, Perez-Alonso M, Artero R, Lopez-Castel A. International Journal of Molecular Sciences. 2023 Jun 6;24(12):9820. doi: 10.3390/ijms24129820. PMID: 37372969

Neuroprotective properties of queen bee acid by autophagy induction. Martínez-Chacón G, Paredes-Barquero M, Yakhine-Diop SMS, Uribe-Carretero E, Bargiela A, Sabater-Arcis M, Morales-García J, Alarcón-Gil J, Alegre-Cortés E, Canales-Cortés S, Rodríguez-Arribas M, Camello PJ, Pedro JMB, Perez-Castillo A, Artero R, Gonzalez-Polo RA, Fuentes JM, Niso-Santano M. Cell Biology and Toxicology. 2023 Jun;39(3):751-770. doi: 10.1007/s10565-021-09625-w. PMID: 34448959

Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression. Gonzalez-Martinez I, Cerro-Herreros E, Moreno N, Garcia-Rey A, Espinosa-Espinosa J, Carrascosa-Saez M, Piqueras-Losilla D, Arzumanov A, Seoane-Miraz D, Jad Y, Raz R, Wood M, Varela M, Llamusi B, Artero R. Molecular Therapy. Nucleic Acids. 2023 Sep 5:34:102024. doi: 10.1016/j.omtn.2023.09.001. PMID: 37744174

Quantitative magnetic resonance imaging assessment of muscle composition in myotonic dystrophy mice. Bargiela A, Ten-Esteve A, Marti-Bonmati L, Sevilla T, Perez Alonso M, Artero R. Scientific Reports. 2023 Jan 10;13(1):503. doi: 10.1038/s41598-023-27661-w. PMID: 36627397

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. Pascual-Gilabert M, Artero R, Lopez-Castel A. Drug Discovery Today. 2023 Jan 9;28(3):103489. doi: 10.1016/j.drudis.2023.103489. PMID: 36634841

Deciphering the complex molecular pathogenesis of myotonic dystrophy type 1 through omics studies. Espinosa-Espinosa J, Gonzalez-Barriga A, Lopez-Castel A, Artero R. International Journal of Molecular Sciences. 2022 Jan 27;23(3):1441. doi: 10.3390/ijms23031441. PMID: 35163365

Moxifloxacin rescues SMA phenotypes in patient-derived cells and animal model. Januel C, Menduti G, Mamchaoui K, Martinat C, Artero R, Konieczny P, Boido M. Cellular and Molecular Life Sciences. 2022 Jul 22;79(8):441. doi: 10.1007/s00018-022-04450-8. PMID: 35864358

Proof of concept of peptide-linked blockmiR-induced MBNL functional rescue in myotonic dystrophy type 1 mouse model. Overby SJ, Cerro Herreros E, Gonzalez Martinez I, Varela MA, Seoane Miraz D, Jad Y, Raz R, Moller T, Perez Alonso M, Wood MJ, Llamusi B, Artero R. Molecular Therapy. Nucleic Acids. 2022 Feb 10;27:1146-1155. doi: 10.1016/j.omtn.2022.02.003. PMID: 35282418

Transgenic overexpression of myocilin leads to variable ocular anterior segment and retinal alterations associated with extracellular matrix abnormalities in adult zebrafish. Atienzar-Aroca R, Ferre-Fernandez J, Tevar A, Bonet-Fernandez J, Cabanero M, Ruiz-Pastor M, Cuenca N, Aroca-Aguilar J, Escribano J. International Journal of Molecular Sciences. 2022 Sep 1;23(17):9989. doi: 10.3390/ijms23179989. PMID: 36077382

Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle. Fernandez-Garibay X, Ortega MA, Cerro-Herreros E, Comelles J, Martinez E, Artero R, Fernandez-Costa JM, Ramon-Azcon J. Biofabrication. 2021 Apr 26;13(3). doi: 10.1088/1758-5090/abf6ae. PMID: 33836519

Defined d-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease. Rapisarda A, Bargiela A, Llamusi B, Pont I, Estrada-Tejedor R, Garcia-Espana E, Artero R, Perez-Alonso M. Scientific Reports. 2021 Sep 30;11(1):19417. doi: 10.1038/s41598-021-98866-0. PMID: 34593893

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Klionsky D, Abdel-Aziz A, Abdelfatah S, et al. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. PMID: 33634751

Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model. Blazquez-Bernal A, Fernandez-Costa JM, Bargiela A, Artero R. FASEB Journal. 2021 Oct;35(10):e21914. doi: 10.1096/fj.202100539RR. PMID: 34547132

Musashi-2 contributes to myotonic dystrophy muscle dysfunction by promoting excessive autophagy through miR-7 biogenesis repression. Sabater-Arcis M, Bargiela A, Moreno N, Poyatos-Garcia J, Vilchez J, Artero R. Molecular Therapy-Nucleic Acids. 2021 Aug 19;25:652-667. doi: 10.1016/j.omtn.2021.08.010. PMID: 34589284

Myotonic dystrophy type 1 drug development: a pipeline toward the market. Pascual-Gilabert M, Lopez-Castel A, Artero R. Drug Discovery Today. 2021 Jul;26(7):1765-1772. doi: 10.1016/j.drudis.2021.03.024. PMID: 33798646

Practicing logical reasoning through drosophila segmentation gene mutants. Bargiela A, Artero R. Biochemistry and Molecular Biology Education. 2021 Sep;49(5):729-736. doi: 10.1002/bmb.21554. PMID: 34160891

Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy. Cerro-Herreros E, Gonzalez-Martinez I, Moreno N, Espinosa-Espinosa J, Fernandez-Costa JM, Colom-Rodrigo A, Overby SJ, Seoane-Miraz D, Poyatos-Garcia J, Vilchez JJ, Lopez de Munain A, Varela MA, Wood MJ, Perez-Alonso M, Llamusi B, Artero R. Molecular Therapy. Nucleic Acids. 2021 Jul 29;26:174-191. doi: 10.1016/j.omtn.2021.07.017. PMID: 34513303

Rabphilin silencing causes dilated cardiomyopathy in a Drosophila model of nephrocyte damage. Selma-Soriano E, Casillas-Serra C, Artero R, Llamusi B, Navarro J, Redon J. Scientific Reports. 2021 Jul 27;11(1):15287. doi: 10.1038/s41598-021-94710-7. PMID: 34315987

Projects
Reference: INVEST/2022/81
Title: Utilización de Drosophila melanogaster en el desarrollo de oligonucleótidos antisentido como medicamentos
Funding body: Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital
Principal Investigator: Arturo López Castell
Duration: 2022 – 2024
Total budget: 66.218 €
Reference: INVEST/2022/63
Title: Especialización en fenotipado y caracterización molecular de modelos biomédicos murinos
Funding body: Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital
Principal Investigator: Rubén Artero Allepuz
Duration: 2022 – 2024
Total budget: 44.812 €
Reference: EIN2020-112137
Title: Del RNA tóxico a la medicina traslacional en Distrofia Miotónica (para la captación de recursos UE)
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Rubén Artero Allepuz
Duration: 2022 – 2022
Total budget: 15.000 €
Reference: DTS22/00088
Title: Optimización de parámetros PK/PD de una terapia farmacológica reutilizada para pacientes con AME
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Rubén Artero Allepuz
Duration: 2022 –
Total budget: 134200
Reference: PI21/00311
Title: Caracterización de una nueva diana terapéutica en disfunción muscular en la distrofia miotónica de tipo 1
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Manuel Pérez Alonso
Duration: 2022 – 2024
Total budget: 141.570 €
Reference: DTS21/00081
Title: Desarrollo preclínico de gapmers contra una nueva diana terapéutica en Distrofia Miotónica
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Manuel Pérez Alonso
Duration: 2022 – 2023
Total budget: 127.600 €
Reference: PLEC2022-009367
Title: Nuevas herramientas en moscas y cultivos en 3D para el desarrollo de oligonucleótidos terapéuticos
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Arturo López Castel
Duration: 2022 – 2024
Total budget: 46.000 €
Reference: MRR/PDC2022-133103-I00
Title: Desarrollo preclínico de un fármaco Gapmer para tratar distrofia miotónica y otras atrofias musculares
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Rubén Artero Allepuz
Duration: 2022 – 2024
Total budget: 149.500 €
Reference: PID2021-125978OB-C22
Title: Comprensión de la atrofia muscular inducida por TNPO3 mutante: modelos preclínicos y aproximaciones terapéuticas en LGMDD2
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Rubén Artero Allepuz
Duration: 2022 – 2025
Total budget: 242.000 €
Reference: INNVA1/2021/44
Title: Reposicionamiento de un fármaco para atrofia muscular espinal
Funding body: Agencia Valenciana de la Innovación-AVI Generalitat Valenciana
Principal Investigator: Rubén Artero Allepuz
Duration: 2021 – 2023
Total budget: 487.727 €
Reference: CI21-00135
Title: Valorization of the repurposing of two drug candidates for spinal muscular atrophy
Funding body: Fundación Bancaria La Caixa
Principal Investigator: Rubén Artero Allepuz
Duration: 2021 – 2023
Total budget: 100.000 €
Reference: GV/2021/014
Title: Caracterización de la contribución de MSI2 a la atrofia muscular de DM1 utilizando nuevos modelos celulares y murinos
Funding body: Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital
Principal Investigator: Ariadna Bargiela Schönbrunn
Duration: 2021 – 2021
Total budget: 10.000 €
Reference: PI-2021-008
Title: miR-OA: Inhibidores de miRNAs como terapia en osteoartritis
Funding body: Universidad de Valencia – INCLIVA
Principal Investigator: Rubén Artero Allepuz, Carmen Carda Batalla
Duration: 2021 – 2022
Total budget: 19.000 €
Reference: PROMETEO/2020/081
Title: Uso de moduladores de microRNAs como terapias experimentales en distrofia miotónica de tipo 1
Funding body: Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital
Principal Investigator: Rubén Artero Allepuz
Duration: 2020 – 2023
Total budget: 193.051 €
Reference: PI19/01796
Title: Implicaciones experimentales y clinicas del complejo proteico rabphilin-rab en daño renal en la diabetes mellitus tipo 2
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Josep Redón i Mas
Duration: 2020 – 2023
Total budget: 196.020 €
Reference: DTS19/00128
Title: Desarrollo preclínico de un fármaco innovador para distrofia miotónica
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Rubén Artero Allepuz
Duration: 2020 – 2022
Total budget: 111.100 €
Reference: PRECIPITA-DM
Title: Desarrollo de una terapia innovadora contra la distrofia miotónica
Funding body: Precipita (Crowdfunding)
Principal Investigator: Rubén Artero Allepuz
Duration: 2020 – 2020
Total budget: 17.703 €
Reference: IAP409
Title: Desarrollo de un modelo en Drosophila de LGMD1F
Funding body: Asociación Conquistando Escalones
Principal Investigator: Rubén Artero Allepuz
Duration: 2019 – 2020
Total budget: 17.303 €
Reference: FIPSE 3544-18
Title: Antisense RNA-therapeutics in Myotonic Dystrophy
Funding body: Fundación para la Innovación y Prospectiva en Salud en España (FIPSE)
Principal Investigator: Rubén Artero Allepuz, Beatriz Llamusí
Duration: 2019 – 2020
Total budget: 25.000 €
Reference: AFM 22346
Title: Development of combinatorial therapies for SMA
Funding body: AFM Telethon
Principal Investigator: Rubén Artero Allepuz
Duration: 2019 – 2020
Total budget: 175000
Reference: RTI2018-094599-B-I00
Title: Comprensión de las causas moleculares de la atrofia muscular en distrofia miotónica tipo 1
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Rubén Artero Allepuz
Duration: 2019 – 2021
Total budget: 185.000 €
Reference: PI17/00352
Title: Modulación terapéutica de los genes MBNL como tratamientos innovadores para distrofia miotónica
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Manuel Pérez Alonso, Beatriz Llamusí Troísi
Duration: 2018 – 2020
Total budget: 75.020 €
Reference: COST Action CA17103 COST-DARTER
Title: COST: European Cooperation in Science and Technology, Delivery of Antisense RNA Therapeutics (DARTER)
Funding body: European Commission
Principal Investigator: Virginia Arechavala
Duration: 2018 – 2022
Total budget: 500.000 €
Reference: HR17-00268
Title: TATAMI (TherApeutic TArgeting of MIrnas) therapeutic targeting of mbnl micrornas as innovative treatments for myotonic dystrophy
Funding body: Fundación Bancaria La Caixa
Principal Investigator: Rubén Artero Allepuz
Duration: 2018 – 2021
Total budget: 997.023 €
+ Info
Title: Desarrollo de modelos experimentales de LGMDD2 y rastreo de fármacos
Doctoral candidate: Blázquez Bernal, Águeda
Director(s): Artero Allepuz, Ruben Darío; Bargiela Schönbrunn, Ariadna
Date of the defense: 14/07/2023
University: University de Valencia

Title: Ruta de la autofagia, MSI2 Y MIR-7 como nuevas dianas terapéuticas para la disfunción muscular en distrofia miotónica de tipo 1
Doctoral candidate: Sabater Arcís, María
Director(s): Artero Allepuz, Rubén; Bargiela Schönbrunn, Ariadna
Date of the defense: 01/04/2022
University: Universitat de València

Title: Proof of concept of therapeutic gene modulation of MBNL1/2 in myotonic dystrophy
Doctoral candidate: Overby, Sarah
Director(s): Artero Allepuz, Rubén
Date of the defense: 21/01/2022
University: Universitat de València

Title: Mejora de la actividad de un hexapéptido anti-dm1 y análisis de las relaciones entre estructura y actividad de hexapéptidos de secuencia similar
Doctoral candidate: Rapisarda, Anna Serafina Rapisarda
Director(s): Artero Allepuz, Ruben Darío
Date of the defense: 31/01/2020
University: Universitat de València

Title: Papel del complejo de proteínas rab-rabphilin en un modelo de daño renal en drosophila
Doctoral candidate: Selma Soriano, Estela
Director(s): Artero Allepuz, Ruben Darío
Date of the defense: 16/01/2020
University: Universitat de València