Sergi Simó, Ph.D.
Research Interests
More than 100 billion neurons form the human central nervous system (CNS). Each is generated in precise numbers, specified with remarkable accuracy, and positioned with exquisite spatial organization to enable complex behaviors such as movement, language, learning, and abstract thought. Nearly all neurons are born and integrated into functional circuits during embryonic development. When neurogenesis or neuronal migration is disrupted, the consequences can range from subtle cognitive impairments to profound structural brain malformations. Despite their prevalence, most neurodevelopmental disorders still lack curative therapies, largely because the molecular mechanisms that govern early brain development remain incompletely understood.
The Simo Lab seeks to uncover the molecular logic that builds the brain. We focus on post-transcriptional regulatory mechanisms that control neuronal production, identity, and positioning. By integrating cutting-edge approaches—including transgenic mouse models, human induced pluripotent stem cells, live time-lapse imaging, super-resolution microscopy, and next-generation sequencing—we investigate how RNA regulation, epitranscriptomic modifications, and proteome homeostasis shape neural development.
Our current research explores how microRNA networks, RNA modifications, and E3 ubiquitin ligase-based protein homeostasis coordinate neurogenesis and neuronal migration. We aim to define how these post-transcriptional programs fine-tune developmental signaling pathways to ensure that the right neurons are produced at the right time and positioned in the right place.
Ultimately, our goal is to bridge fundamental developmental neurobiology with translational insight. By understanding how the CNS is assembled under normal conditions, we lay the groundwork for innovative therapeutic strategies for neurodevelopmental disorders.
Specialties/Focus
- Developmental Biology
- miRNA Biology and Epitranscriptomics
- Proteomics
Graduate Group Affiliations
Soto DC, Uribe-Salazar JM, Kaya G, Valdarrago R, Sekar A, Haghani NK, Hino K, La G, Mariano NAF, Ingamells C, Baraban A, Jamal Z, Turner TN, Green ED, Simó S, Quon G, Andrés AM, Dennis MY. "Human-specific gene expansions contribute to brain evolution". Cell. 2025 Sep 18;188(19):5363-5383.e22.
Flores-Tamez VA, Martín-Aragón Baudel M, Hong J, Taylor JL, Ren L, Le T, Syed AU, Moustafa Y, Singhrao N, Lemus-Martinez WR, Reddy GR, Ramer V, Man KNM, Bartels P, Chen-Izu Y, Chen CY, Simo S, Dickson EJ, Morotti S, Grandi E, Santana LF, Hell JW, Horne MC, Nieves-Cintrón M, Navedo MF. "α1(C) S1928 Phosphorylation of Ca(V)1.2 Channel Controls Vascular Reactivity and Blood Pressure". J Am Heart Assoc. 2024 Oct 15;13(20):e035375. doi: 10.1161/JAHA.124.035375.
Uribe-Salazar JM, Kaya G, Weyenberg K, Radke B, Hino K, Soto DC, Shiu JL, Zhang W, Ingamells C, Haghani NK, Xu E, Rosas J, Simó S, Miesfeld J, Glaser T, Baraban SC, Jao LE, Dennis MY. "Zebrafish models of human-duplicated SRGAP2 reveal novel functions in microglia and visual system development". bioRxiv. 2024 Sep 27;.
Krueger MR, Fishman-Williams E, Simó S, Tarantal AF, La Torre A. "Expression patterns of CYP26A1, FGF8, CDKN1A, and NPVF in the developing rhesus monkey retina". Differentiation. 2024 Jan-Feb;135:100743. doi: 10.1016/j.diff.2023.100743.
Horvath JD, Casas M, Kutchukian C, Sánchez SC, Pergande MR, Cologna SM, Simó S, Dixon RE, Dickson EJ. "α-Synuclein-dependent increases in PIP5K1γ drive inositol signaling to promote neurotoxicity". Cell Rep. 2023 Oct 31;42(10):113244.
Ortega-Gascó A, Parcerisas A, Hino K, Herranz-Pérez V, Ulloa F, Elias-Tersa A, Bosch M, García-Verdugo JM, Simó S, Pujadas L, Soriano E. "Regulation of young-adult neurogenesis and neuronal differentiation by neural cell adhesion molecule 2 (NCAM2)". Cereb Cortex. 2023 Oct 14;33(21):10931-10948.
Casas M, Murray KD, Hino K, Vierra NC, Simó S, Trimmer JS, Dixon RE, Dickson EJ. "NPC1-dependent alterations in K(V)2.1-Ca(V)1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease". Nat Commun. 2023 Jul 28;14(1):4553.
Han JS, Fishman-Williams E, Decker SC, Hino K, Reyes RV, Brown NL, Simó S, Torre A. "Notch directs telencephalic development and controls neocortical neuron fate determination by regulating microRNA levels". Development. 2023 Jun 1;150(11).
Reyes RV, Hino K, Canales CP, Dickson EJ, La Torre A, Simó S. "The E3 Ubiquitin Ligase CRL5 Regulates Dentate Gyrus Morphogenesis, Adult Neurogenesis, and Animal Behavior". Front Neurosci. 2022;16:908719.
Sekar A, Sanches TM, Hino K, Kumar M, Wang J, Ha E, Durbin-Johnson B, Simó S, Dennis MY. "RapID Cell Counter: Semi-Automated and Mid-Throughput Estimation of Cell Density within Diverse Cortical Layers". eNeuro. 2021 Nov-Dec;8(6).
Tiscione SA, Casas M, Horvath JD, Lam V, Hino K, Ory DS, Santana LF, Simó S, Dixon RE, Dickson EJ. "IP(3)R-driven increases in mitochondrial Ca(2+) promote neuronal death in NPC disease". Proc Natl Acad Sci U S A. 2021 Oct 5;118(40).
Kutchukian C, Vivas O, Casas M, Jones JG, Tiscione SA, Simó S, Ory DS, Dixon RE, Dickson EJ. "NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes". EMBO J. 2021 Jul 1;40(13):e105990.
Fishman ES, Louie M, Miltner AM, Cheema SK, Wong J, Schlaeger NM, Moshiri A, Simó S, Tarantal AF, La Torre A. "MicroRNA Signatures of the Developing Primate Fovea". Front Cell Dev Biol. 2021;9:654385. doi: 10.3389/fcell.2021.654385. eCollection 2021.
Han JS, Hino K, Li W, Reyes RV, Canales CP, Miltner AM, Haddadi Y, Sun J, Chen CY, La Torre A, Simó S. "CRL5-dependent regulation of the small GTPases ARL4C and ARF6 controls hippocampal morphogenesis". Proc Natl Acad Sci U S A. 2020 Sep 15;117(37):23073-23084.
Parcerisas A, Pujadas L, Ortega-Gascó A, Perelló-Amorós B, Viais R, Hino K, Figueiro-Silva J, La Torre A, Trullás R, Simó S, Lüders J, Soriano E. "NCAM2 Regulates Dendritic and Axonal Differentiation through the Cytoskeletal Proteins MAP2 and 14-3-3". Cereb Cortex. 2020 May 18;30(6):3781-3799.
Monroy BY, Tan TC, Oclaman JM, Han JS, Simó S, Niwa S, Nowakowski DW, McKenney RJ, Ori-McKenney KM. "A Combinatorial MAP Code Dictates Polarized Microtubule Transport". Dev Cell. 2020 Apr 6;53(1):60-72.e4.
Fairchild CLA, Cheema SK, Wong J, Hino K, Simó S, La Torre A. "Let-7 regulates cell cycle dynamics in the developing cerebral cortex and retina". Sci Rep. 2019 Oct 25;9(1):15336.
Tan R, Lam AJ, Tan T, Han J, Nowakowski DW, Vershinin M, Simó S, Ori-McKenney KM, McKenney RJ. "Microtubules gate tau condensation to spatially regulate microtubule functions". Nat Cell Biol. 2019 Sep;21(9):1078-1085.
Prada MP, Syed AU, Buonarati OR, Reddy GR, Nystoriak MA, Ghosh D, Simó S, Sato D, Sasse KC, Ward SM, Santana LF, Xiang YK, Hell JW, Nieves-Cintrón M, Navedo MF. "A G(s)-coupled purinergic receptor boosts Ca(2+) influx and vascular contractility during diabetic hyperglycemia". Elife. 2019 Mar 1;8.
Hino K, Simó S, Cooper JA. "Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis". Dev Dyn. 2018 Nov;247(11):1227-1236.
Fairchild CL, Hino K, Han JS, Miltner AM, Peinado Allina G, Brown CE, Burns ME, La Torre A, Simó S. "RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion". Development. 2018 Feb 2;145(3).
Teckchandani A, Laszlo GS, Simó S, Shah K, Pilling C, Strait AA, Cooper JA. "Cullin 5 destabilizes Cas to inhibit Src-dependent cell transformation". J Cell Sci. 2014 Feb 1;127(Pt 3):509-20.
Simó S, Cooper JA. "Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors". Dev Cell. 2013 Nov 25;27(4):399-411.
Simó S, Cooper JA. "Regulation of dendritic branching by Cdc42 GAPs". Genes Dev. 2012 Aug 1;26(15):1653-8.
Simó S, Jossin Y, Cooper JA. "Cullin 5 regulates cortical layering by modulating the speed and duration of Dab1-dependent neuronal migration". J Neurosci. 2010 Apr 21;30(16):5668-76.
Feng L, Allen NS, Simo S, Cooper JA. "Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development". Genes Dev. 2007 Nov 1;21(21):2717-30.
Simó S, Pujadas L, Segura MF, La Torre A, Del Río JA, Ureña JM, Comella JX, Soriano E. "Reelin induces the detachment of postnatal subventricular zone cells and the expression of the Egr-1 through Erk1/2 activation". Cereb Cortex. 2007 Feb;17(2):294-303.