Photo of Bernardo Sabatini,  MD, PhD

Bernardo Sabatini, MD, PhD

Harvard Medical School

Harvard Medical School

Bernardo Sabatini, MD, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Alice and Rodman W. Moorhead III Professor of Neurobiology, Neurobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our laboratory studies the function of the PI3K/TSC/mTOR pathway within neurons and astrocytes. Our goal is to understand how this pathway regulates the growth and function of cells within the mammalian central nervous system. Furthermore, we wish to understand how loss of PTEN or TSC1/2, as occurs in the hamaratomatos disorders of Cowden's disease and Tuberous Sclerosis Complex, perturb the growth and function of neurons. Our studies include biochemical analysis of the signaling pathway, quantitative analysis of cell-growth and morphology, as well as electrophysiological analysis of neuronal function. Our initial studies have revealed a role of the TSC pathway in controlling neuronal growth and function and have found novel links from TSC/mTOR to the regulation of the actin cytoskeleton via the depolymerization factor cofilin.

Publications

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  • Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, Plovanich ME, Yuan ED, Jones TD, Chantranupong L, Comb W, Wang T, Bar-Peled L, Zoncu R, Straub C, Kim C, Park J, Sabatini BL, Sabatini DM. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 2015; 347:188-94. PubMed
  • Tang JC, Szikra T, Kozorovitskiy Y, Teixiera M, Sabatini BL, Roska B, Cepko CL. A nanobody-based system using fluorescent proteins as scaffolds for cell-specific gene manipulation. Cell 2013; 154:928-39. PubMed
  • Beier KT, Saunders AB, Oldenburg IA, Sabatini BL, Cepko CL. Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo. Front Neural Circuits 2013; 7:11. PubMed
  • Tritsch NX, Ding JB, Sabatini BL. Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 2012; 490:262-6. PubMed
  • Kozorovitskiy Y, Saunders A, Johnson CA, Lowell BB, Sabatini BL. Corrigendum: Recurrent network activity drives striatal synaptogenesis. Nature 2012. PubMed
  • Kozorovitskiy Y, Saunders A, Johnson CA, Lowell BB, Sabatini BL. Recurrent network activity drives striatal synaptogenesis. Nature 2012; 485:646-50. PubMed
  • Cheng J, Zhou X, Miller EL, Alvarez VA, Sabatini BL, Wong ST. Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images. Neuroinformatics 2010; 8:157-70. PubMed
  • Higley MJ, Sabatini BL. Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors. Nat Neurosci 2010; 13:958-66. PubMed
  • Sturgill JF, Steiner P, Czervionke BL, Sabatini BL. Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking. J Neurosci 2009; 29:12845-54. PubMed
  • Higley MJ, Soler-Llavina GJ, Sabatini BL. Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration. Nat Neurosci 2009; 12:1121-8. PubMed
  • Bloodgood BL, Giessel AJ, Sabatini BL. Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines. PLoS Biol. 2009; 7:e1000190. PubMed
  • Ding JB, Takasaki KT, Sabatini BL. Supraresolution imaging in brain slices using stimulated-emission depletion two-photon laser scanning microscopy. Neuron 2009; 63:429-37. PubMed
  • Steiner P,Higley MJ,Xu W,Czervionke BL,Malenka RC,Sabatini BL. Destabilization of the postsynaptic density by PSD-95 serine 73 phosphorylation inhibits spine growth and synaptic plasticity. Neuron 2008; 60:788-802. PubMed
  • Han S, Witt RM, Santos TM, Polizzano C, Sabatini BL, Ramesh V. Pam (Protein associated with Myc) functions as an E3 Ubiquitin ligase and regulates TSC/mTOR signaling. Cell Signal 2008; 20:1084-91. PubMed
  • Busetto G, Higley MJ, Sabatini BL. Developmental presence and disappearance of postsynaptically silent synapses on dendritic spines of rat layer 2/3 pyramidal neurons. J Physiol 2008; 586:1519-27. PubMed
  • Bloodgood BL, Sabatini BL. Regulation of synaptic signalling by postsynaptic, non-glutamate receptor ion channels. J Physiol 2007; 586:1475-80. PubMed
  • Xu W, Schluter OM, Steiner P, Czervionke BL, Sabatini B, Malenka RC. Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD. Neuron 2008; 57:248-62. PubMed
  • Sabatini BL. Neuroscience: neighbourly synapses. Nature 2007; 450:1173-5. PubMed
  • Cheng J, Zhou X, Miller E, Witt RM, Zhu J, Sabatini BL, Wong ST. A novel computational approach for automatic dendrite spines detection in two-photon laser scan microscopy. J Neurosci Methods 2007; 165:122-34. PubMed
  • Carter AG, Soler-Llavina GJ, Sabatini BL. Timing and location of synaptic inputs determine modes of subthreshold integration in striatal medium spiny neurons. J Neurosci 2007; 27:8967-77. PubMed
  • Alvarez VA, Ridenour DA, Sabatini BL. Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability. J Neurosci 2007; 27:7365-76. PubMed
  • Zhang Y, Zhou X, Witt RM, Sabatini BL, Adjeroh D, Wong ST. Dendritic spine detection using curvilinear structure detector and LDA classifier. Neuroimage 2007; 36:346-60. PubMed
  • Bloodgood BL, Sabatini BL. Ca(2+) signaling in dendritic spines. Curr Opin Neurobiol 2007; 17:345-51. PubMed
  • Alvarez VA, Ridenour DA, Sabatini BL. Retraction of synapses and dendritic spines induced by off-target effects of RNA interference. J Neurosci 2006; 26:7820-5. PubMed
  • Soler-Llavina GJ, Sabatini BL. Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 2006; 9:798-806. PubMed
  • Zhou X, Zhu J, Liu KY, Sabatini BL, Wong ST. Mutual information-based feature selection in studying perturbation of dendritic structure caused by TSC2 inactivation. Neuroinformatics 2006; 4:81-94. PubMed
  • Tavazoie SF, Alvarez VA, Ridenour DA, Kwiatkowski DJ, Sabatini BL. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 2005; 8:1727-34. PubMed
  • Bloodgood BL, Sabatini BL. Neuronal activity regulates diffusion across the neck of dendritic spines. Science 2005; 310:866-9. PubMed
  • Carter AG, Sabatini BL. State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 2004; 44:483-93. PubMed
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