Dr. Juan Pablo Fededa

Investigador Asistente CONICET
Profesor Adjunto DS (UNSAM)
jfededa@iib.unsam.edu.ar

http://www.fededalab.net

En la última década, los programas transcripcionales responsables de dirigir el desarrollo del cerebro fueron en su mayor parte descubiertos. Aun así, el rol de los mecanismos post-transcripcionales en la regulación del desarrollo de este órgano recién están empezando a ser conocidos. Nosotros queremos caracterizar el impacto de la regulación por microRNAs sobre la expresión génica durante los procesos celulares esenciales en el desarrollo cerebrocortical mamífero. En particular, estamos estudiando como los microRNAs interactúan con programas transcripcionales para coordinar el desarrollo del cortex. Utilizando técnicas en el estado del arte, desde crivados de alto contenido por imágenes a la edición de genes in vivo mediante cRISPR/Cas9, investigamos microRNAs y factores de función desconocida que están implicados en la patogénesis de desórdenes neurocognitivos del desarrollo. Nuestros estudios van a enriquecer la comprensión de las vías de diferenciación durante el desarrollo cerebrocortical y permitirán una mejor caracterización de la génesis de estos desordenes asociados al desarrollo cerebrocortical.

In the last decade, the transcriptional programs responsible to drive the development of the brain were mostly unveiled. Yet, the role of the post-transcriptional mechanisms regulating the development of this organ remains largely unknown. We want to characterize the impact of microRNA regulation over gene expression during essential cellular processes in mammalian cerebrocortical development. In particular, we are studying how microRNAs are interacting with transcriptional programs in order to coordinate cortex development. Using state of the art techniques ranging from high content imaging screens to in vivo CRISPR/Cas9 gene editing in mice, we are investigating microRNAs and factors of unknown function that are implicated in the pathogenesis of neurocognitive disorders. Our studies will enrich the understanding of the differentiation pathways during cerebrocortical development and allow a better characterization of the genesis of conditions with neurodevelopmental origin.

1. microRNA-34/449 controls mitotic spindle orientation during mammalian cortex development; JP Fededa*, C Esk, B Mierzwa, R Stanyte, S Yuan, H Zheng, W Yan, JA Knoblich & DW Gerlich*(*: autores co-correspondientes); EMBO Journal, 35 (22), 2386-98, 2016 (artículo de tapa).
2. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells; M Paolino, A Choidas, S Wallner, B Pranjic, I Uribesalgo, S Loeser, AM Jamieson, WY Langdon, F Ikeda, JP Fededa, SJ Cronin, R Nitsch, C Schultz-Fademrecht, J Eickhoff, S Menninger, A Unger, R Torka, T Gruber, R Hinterleitner, G Baier, D Wolf, A Ullrich, BM Klebl , JM Penninger; Nature. 507(7493), 508-12, 27, 2014.
3. Unsupervised modeling of cell morphology dynamics for time-lapse microscopy; Q Zhong, AG Busetto, JP Fededa, JM Buhmann, DW Gerlich; Nature Methods 9 (7), 711-713, 22, 2012.
4. Molecular control of animal cell cytokinesis; JP Fededa, DW Gerlich; Nature Cell Biology 14 (5), 440-447, 123, 2012.
5. Nuclear factor (NF)-κB controls expression of the immunoregulatory glycan-binding protein galectin-1; MA Toscano, L Campagna, LL Molinero, JP Cerliani, DO Croci, JM Ilarregui, MB Fuertes, IM Nojek, JP Fededa, NW Zwirner, MA Costas, GA Rabinovich; Molecular Immunology 48 (15), 1940-1949, 16, 2011.
6. RNA polymerase II elongation at the crossroads of transcription and alternative splicing; M de la Mata, MJ Muñoz, M Alló, JP Fededa, IE Schor, AR Kornblihtt; Genetics research international 20, 2011.
7. Control of alternative splicing through siRNA-mediated transcriptional gene silencing; M Alló, V Buggiano, JP Fededa, E Petrillo, I Schor, M de la Mata, E Agirre, M Plass, E Eyras, SA Elela, R Klinck, B Chabot, AR Kornblihtt; Nature Structural & Molecular Biology 16 (7), 717-724, 206, 2009.
8. A splicing regulator promotes transcriptional elongation; JP Fededa, AR Kornblihtt; Nature Structural & Molecular Biology 15 (8), 779-781, 13, 2008.
9. A polar mechanism coordinates different regions of alternative splicing within a single gene; JP Fededa, E Petrillo, MS Gelfand, AD Neverov, S Kadener, G Nogués, F Pelisch, FE Baralle, AF Muro, AR Kornblihtt; Molecular Cell 19 (3), 393-404, 48, 2005.
10. A slow RNA polymerase II affects alternative splicing in vivo; M de la Mata, CR Alonso, S Kadener, JP Fededa, M Blaustein, F Pelisch, P Cramer, D Bentley, AR Kornblihtt; Molecular Cell 12 (2), 525-532, 454, 2003.
11. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation; S Kadener, JP Fededa, M Rosbash, AR Kornblihtt; Proceedings of the National Academy of Sciences 99 (12), 8185-8190, 99, 20