NEURODEVELOPMENTAL DISORDERS

Principal Investigators

Sandra Acosta

Assistant Professor Serra Hunter

Functional neurogenomics

Soledad Alcantara

Full Professor

Biomimetic strategies for driving neural development and regeneration

Alberto Ortega

Ramon y Cajal Researcher (Assistant Professor)

Human modeling of neurological disorders

Research team

 

Aida Castellanos

Postdoctoral Researcher

 

Hector Gaitan

Postdoctoral Researcher

 

Marta Alonso

Early Stage Researcher

 

Laura Ferigle

Early Stage Researcher

 

Adria Pla

Early Stage Researcher

 

Jose Pablo Soriano

Early Stage Researcher

 

Efren Xicoy

Early Stage Researcher

 

Isabel Turpin

Technician

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

Featured Projects

 

    • Helping the brain to rebuild itself: Understanding physical and metabolic properties of neurogenic niches in search for regenerative therapies for the damaged brain. Ministerio de Economía y Competitividad. BFU2017-83435-R. Soledad Alcantara

 

    • i4KIDS, Pediatric Innovation HUB. Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR). Generalitat de Catalunya. Soledad Alcantara

 

    • MeCP2 protein function: Implications in s. MECP2 duplication and s.Rett. Fundació Privada per a la Recerca i la Docencia Sant Joan de Déu. PFNR00085. Judith Armstrong, Soledad Alcantara

 

    • Molecular analysis of the non-cell autonomous effects in Down Syndrome cortex using mouse ESC-derived brain organoids. Fondation LeJeune. Sandra Acosta

 

    • RYC2019-026980-I and University of Barcelona associated Welcome package. Alberto Ortega

 

    • 3D human organoids for drug repurposing and biomarker identification in COVID-19. Merck_Special COVID19 program. Sandra Acosta

Featured Publications

 

    • 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

 

    • 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., Laayouni, H., Segarra-Casas, A., Bertranpetit, J., Guigó, R., & Acosta, S. (2020). Intronic enhancers regulate the expression of genes involved in tissue-specific functions and homeostasis. bioRxiv. https://doi.org/10.1101/2020.08.21.260836

 

    • Ortega, J. A., Daley, E. L., Kour, S., Samani, M., Tellez, L., Smith, H. S., Hall, E. A., Esengul, Y. T., Tsai, Y.-H., Gendron, T. F., Donnelly, C. J., Siddique, T., Savas, J. N., Pandey, U. B., & Kiskinis, E. (2020). Nucleocytoplasmic Proteomic Analysis Uncovers eRF1 and Nonsense-Mediated Decay as Modifiers of ALS/FTD C9orf72 Toxicity. Neuron, 106(1), 90-107.e13. https://doi.org/https://doi.org/10.1016/j.neuron.2020.01.020

 

    • 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

 

    • Ziller, M. J., Ortega, J. A., Quinlan, K. A., Santos, D. P., Gu, H., Martin, E. J., Galonska, C., Pop, R., Maidl, S., Di Pardo, A., Huang, M., Meltzer, H. Y., Gnirke, A., Heckman, C. J., Meissner, A., & Kiskinis, E. (2018). Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology. Cell Stem Cell, 22(4), 559–574.e9. https://doi.org/10.1016/j.stem.2018.02.012

 

    • Ortega, J. A., Memi, F., Radonjic, N., Filipovic, R., Bagasrawala, I., Zecevic, N., & Jakovcevski, I. (2018). The Subventricular Zone: A Key Player in Human Neocortical Development. The Neuroscientist , 24(2), 156–170.

 

    • Acosta, S., Fiore, L., Carota, I. A., & Oliver, G. (2018). Use of two gRNAs for CRISPR/Cas9 improves bi-allelic homologous recombination efficiency in mouse embryonic stem cells. Genesis, 56(5), e23212. https://doi.org/10.1002/dvg.23212

 

    • Ortega, J. A., Sirois, C. L., Memi, F., Glidden, N., & Zecevic, N. (2016). Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells. Cerebral Cortex, 27(7), 3736–3751. https://doi.org/10.1093/cercor/bhw194

 

    • Geng, X., Acosta, S., Lagutin, O., Gil, H. J., & Oliver, G. (2016). Six3 dosage mediates the pathogenesis of holoprosencephaly. Development, 143(23), 4462–4473. https://doi.org/10.1242/dev.132142

Knowledge transfer & Innovation

 

    • Artificial Intelligence applied to organoids for drug discovery. AGAUR-Llavor. Sandra Acosta

 

    • Artificial Intelligence applied to organoids for drug discovery. INNOValora. Sandra Acosta

 

    • Caixa Impulse Validate. Sandra Acosta

 

    • Dynamics within supramolecular matrices enhance functional maturation of human iPSCs-derived neurons and regeneration. Northwestern University transferred to Amphix Bio, Inc. Serial Number 62/796,425. Utility U.S. Zaida Alvarez Pinto, Juan Alberto Ortega Cano, Kohei Sato, Evangelos Kiskinis, Samuel I. Stupp.

 

    • OrganAId: Artificial Intelligence-based tool for the study of brain organoids. Patent in preparation (UPF-Innova)-Currently Trade Secret. Sandra Acosta i Oscar Lao.

 

    • Two gRNA-Cas9 method for homologous recombination-based gene targeting. US Prov 62501490. Sandra Acosta i Guillermo Oliver