Michael Greenberg

Michael Greenberg, Ph.D.

Nathan Marsh Pusey Professor of Neurobiology, Harvard Medical School
Professor of Neurology, Boston Children's Hospital
Director of the Hock E. Tan and K. Lisa Yang Center for Autism Research, Harvard Medical School

How Experience Shapes Gene Expression & Connectivity in the Brain

Our interactions with the outside world trigger changes in neurons that are critical for proper brain development and higher cognitive function. Experience-driven neuronal activity shapes gene expression in ways that promote the maturation and refinement of neural circuits.

The Greenberg lab studies precisely how, at a molecular level, neuronal activity controls gene expression and connectivity in the brain. A number of human brain developmental disorders, including autism and Rett syndrome, have now been linked to abnormalities in experience-driven brain pathways. Our lab studies the underlying basis of such neurological disorders.

Beginning in the mid-1980s, with the appreciation that growth factors trigger rapid transcription of an important activity-responsive gene called Fos, we have focused on elucidating the nature and role of neuronal transcriptional programs triggered by extracellular stimuli. In this effort, we have discovered various signaling pathways that convey neurotrophin and calcium-dependent signals from distal synapses (far from the cell body) to the nucleus of neurons, where transcription occurs. We have also studied the role of these activity-regulated transcriptional programs in modulating the plasticity of brain circuits.

Given the strong links between these processes and various human disorders of cognitive function, we continually seek to exploit our molecular insights to advance understanding of clinically relevant neurological conditions. Current projects in the lab include studies of sensory-driven circuit development, the role of enhancer elements in activity-dependent transcriptional responses, human-specific molecular neurobiology and the function of MeCP2, the gene mutated in Rett syndrome.

Publications View
Experience influences the refinement of feature selectivity in the mouse primary visual thalamus.
Authors: Authors: Sonoda T, Stephany CÉ, Kelley K, Kang D, Wu R, Uzgare MR, Fagiolini M, Greenberg ME, Chen C.
Neuron
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FOS binding sites are a hub for the evolution of activity-dependent gene regulatory programs in human neurons.
Authors: Authors: Carter AC, Koreman GT, Petrocelli JE, Robb JE, Bushinsky EM, Trowbridge SK, Kingsley DM, Walsh CA, Song JHT, Greenberg ME.
bioRxiv
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Human-chimpanzee tetraploid system defines mechanisms of species-specific neural gene regulation.
Authors: Authors: Song JHT, Carter AC, Bushinsky EM, Beck SG, Petrocelli JE, Koreman GT, Babu J, Kingsley DM, Greenberg ME, Walsh CA.
bioRxiv
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Novel environment exposure drives temporally defined and region-specific chromatin accessibility and gene expression changes in the hippocampus.
Authors: Authors: Traunmüller L, Duffy EE, Liu H, Sanalidou S, Assad EG, Sun S, Pajarillo NS, Niu N, Griffith EC, Greenberg ME.
bioRxiv
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Structural basis for the midnolin-proteasome pathway and its role in suppressing myeloma.
Authors: Authors: Nardone C, Gao J, Seo HS, Mintseris J, Ort L, Yip MCJ, Negasi M, Besschetnova AK, Kamitaki N, Gygi SP, Dhe-Paganon S, Munshi N, Fulciniti M, Greenberg ME, Shao S, Elledge SJ, Gu X.
bioRxiv
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Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.
Authors: Authors: Nagy MA, Price S, Wang K, Gill S, Ren E, Jayne L, Pajak V, Deighan S, Liu B, Lu X, Diallo A, Lo SC, Kleiman R, Henderson C, Suh J, Griffith EC, Greenberg ME, Hrvatin S.
Proc Natl Acad Sci U S A
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Interaction of methyl-CpG-binding protein 2 (MeCP2) with distinct enhancers in the mouse cortex.
Authors: Authors: Mishra GP, Sun EX, Chin T, Eckhardt M, Greenberg ME, Stroud H.
Nat Neurosci
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Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord.
Authors: Authors: Nagy MA, Price S, Wang K, Gill SP, Ren E, McElrath L, Pajak V, Deighan S, Liu B, Liu X, Diallo A, Lo SC, Kleiman R, Henderson C, Suh J, Griffith EC, Greenberg ME, Hrvatin S.
bioRxiv
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Neuronal enhancers fine-tune adaptive circuit plasticity.
Authors: Authors: Griffith EC, West AE, Greenberg ME.
Neuron
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Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration.
Authors: Authors: Hochbaum DR, Hulshof L, Urke A, Wang W, Dubinsky AC, Farnsworth HC, Hakim R, Lin S, Kleinberg G, Robertson K, Park C, Solberg A, Yang Y, Baynard C, Nadaf NM, Beron CC, Girasole AE, Chantranupong L, Cortopassi MD, Prouty S, Geistlinger L, Banks AS, Scanlan TS, Datta SR, Greenberg ME, Boulting GL, Macosko EZ, Sabatini BL.
Cell
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