Research Interest

The development of the central nervous system is strictly modulated by genetic and environmental factors in a spatial-temporal fashion. Even mild disturbances in genes and/or environmental cues during critical periods of the pre- and post-natal development, lead to morphological and functional anomalies that will compromise the normal behaviour and cognitive function. By identifying risk factors and investigating their role in the central nervous system development, utilizing cutting-edge in vitro and in vivo technologies, this programme aims to design new and more effective strategies for therapeutic intervention.

Technologies & Methods

• Primary rodent and human neural cell cultures
• Reprogramming and Stem Cell Technologies
• CRISPR gene editing
• In utero electroporation
• Immunolabeling and in situ hybridisation in tissue and cell systems
• High-resolution microscopy
• Flow cytometry
• Mass-spectrometry
• Protein and RNA Molecular biology: Western Blot, Dot Blot, qPCR, Immunoprecipitation assays
• Bulk and Single-cell transcriptomics
• In vivo models of brain injury
• Intracerebral injection and implantation
• Image analysis

Active Projects

• • Artificial Intelligence applied to organoids for drug discovery. Generalitat de Catalunya. 2019 llavor-121. Sandra Acosta

• • Caracterización proteomica de los microambientes de la corteza cerebral humana durante el desarrollo: implicaciones evolutivas y clínicas. Ministerio de Ciencia e Innovación. PID2020-114407RA-I00. Alberto Ortega.

• • Defining the spinal cord matrisome to design more effective ALS models and treatments. Association Française contre les Myopathies. #23648. Alberto Ortega.

• • Modelado del control ambiental de la diferenciación de los progenitores neurales: un punto de encuentro entre los trastornos del desarrollo y la regeneración neural. Ministerio de Ciencia e Innovación. PID2020-115748RB-I00. Soledad Alcantara

• • Molecular analysis of the non-cell autonomous effects in Down syndrome cortex using. Fondation Jerome Lejeune. 1917. Sandra Acosta

• • Neurodegeneration triggered by SARS-CoV-2: brain organoids as an analytical and predictive model (NeuroCOVID). Fundació La Marató de TV3. 772/U/2021. Sandra Acosta

• • 2 Confidential agreement.

Selected Publications

• • Álvarez, Z., Kolberg-Edelbrock, A. N., Sasselli, I. R., Ortega, J. A., Qiu, R., Syrgiannis, Z., Mirau, P. A., Chen, F., Chin, S. M., Weigand, S., Kiskinis, E., & Stupp, S. I. (2021). Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury. Science, 374(6569), 848–856. https://doi. org/10.1126/science.abh3602

• • Balada, R., Tebé, C., León, M., Arca, G., Alsina, M., Castells, A. A., Alcántara, S., & Garcia-Alix, A. (2020). Enquiring beneath the surface: can a gene expression assay shed light into the heterogeneity among newborns with neonatal encephalopathy?. Pediatric Research, 88(3), 451–458. https://doi.org/10.1038/s41390-020-0764-2

• • Borsari, B., Villegas-Mirón, P., Pérez-Lluch, S., Turpin, I., Laayouni, H., Segarra-Casas, A., Bertranpetit, J., Guigó, R., & Acosta, S. (2021). Enhancers with tissue-specific activity are enriched in intronic regions. Genome Research, 31(8), 1325–1336. https://doi.org/10.1101/gr.270371.120

• • Castells, A. A., Balada, R., Tristán-Noguero, A., O’Callaghan, M., Cortès-Saladelafont, E., Pascual-Alonso, A., Garcia-Cazorla, À., Armstrong, J., & Alcántara, S. (2021). Unraveling Molecular Pathways Altered in MeCP2-Related Syndromes, in the Search for New Potential Avenues for Therapy. Biomedicines, 9(2), 148. https://doi.org/10.3390/biomedicines9020148

• • Castells AA., Gueraldi D., Balada R., Tristán-Noguero A., Cortès-Saladelafont E., Ramos F., Meavilla S., De Los Santos M., Garcia-Volpe C., Colomé R., Couce ML., Sierra C., Ormazábal A., Batllori M., Artuch R., Armstrong J., Alcántara S., & Garcia-Cazorla À. (2019). Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism. Scientifics Reports, 9 (9128). https://doi.org/10.1038/s41598-019-45674-2

• • Farré, X., Molina, R., Barteri, F., Timmers, P., Joshi, P. K., Oliva, B., Acosta, S., Esteve-Altava, B., Navarro, A., & Muntané, G. (2021). Comparative Analysis of Mammal Genomes Unveils Key Genomic Variability for Human Life Span. Molecular Biology and Evolution, 38(11), 4948–4961. https://doi.org/10.1093/molbev/msab219

• •  Simkin, D., Marshall, K. A., Vanoye, C. G., Desai, R. R., Bustos, B. I., Piyevsky, B. N., Ortega, J. A., Forrest, M., Robertson, G. L., Penzes, P., Laux, L. C., Lubbe, S. J., Millichap, J. J., George, A. L., Jr, & Kiskinis, E. (2021). Dyshomeostatic modulation of Ca2+- activated K+ channels in a human neuronal model of KCNQ2 encephalopathy. eLife, 10, e64434. https://doi.org/10.7554/eLife.64434

• • Villegas-Mirón, P., Acosta, S., Nye, J., Bertranpetit, J., & Laayouni, H. (2021). Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers. Frontiers in Genetics, 12, 714491. https://doi.org/10.3389/fgene.2021.714491

Knowledge transfer & Innovation

• • Cynamics within supramolecular IKVAV Matrices Enhance Functional Maturation of Human iPSCSs-derived Neurons and Regeneration. Zaida Alvarez, Alberto Ortega, Kohei Sato, Evangelos Kiskinis, Samuel I. Stupp