Michael Greenberg

Michael Greenberg, PhD

Nathan Marsh Pusey Professor of Neurobiology

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
Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice.
Authors: Authors: Vera R, Hong N, Jiang B, Liang G, Eckenhoff MF, Kincaid HJ, Browne V, Chellaraj V, Gisewhite D, Greenberg M, Ranjan S, Zhu G, Wei H.
J Alzheimers Dis
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Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement.
Authors: Authors: Tzeng CP, Whitwam T, Boxer LD, Li E, Silberfeld A, Trowbridge S, Mei K, Lin C, Shamah R, Griffith EC, Renthal W, Chen C, Greenberg ME.
Proc Natl Acad Sci U S A
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The Impact of COVID-19 on Multidisciplinary Care Delivery to Children with Cerebral Palsy and Other Neuromuscular Complex Chronic Conditions.
Authors: Authors: Nguyen HB, Mulpuri N, Cook D, Greenberg M, Shrader MW, Sanborn R, Mulpuri K, Shore BJ.
Children (Basel)
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The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation.
Authors: Authors: Gu X, Nardone C, Kamitaki N, Mao A, Elledge SJ, Greenberg ME.
Science
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Thyroid hormone rewires cortical circuits to coordinate body-wide metabolism and exploratory drive.
Authors: Authors: Hochbaum DR, Dubinsky AC, Farnsworth HC, Hulshof L, Kleinberg G, Urke A, Wang W, Hakim R, Robertson K, Park C, Solberg A, Yang Y, Baynard C, Nadaf NM, Beron CC, Girasole AE, Chantranupong L, Cortopassi M, Prouty S, Geistlinger L, Banks A, Scanlan T, Greenberg ME, Boulting GL, Macosko EZ, Sabatini BL.
bioRxiv
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A cell-type-specific error-correction signal in the posterior parietal cortex.
Authors: Authors: Green J, Bruno CA, Traunmüller L, Ding J, Hrvatin S, Wilson DE, Khodadad T, Samuels J, Greenberg ME, Harvey CD.
Nature
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Activity-Induced MeCP2 Phosphorylation Regulates Retinogeniculate Synapse Refinement.
Authors: Authors: Tzeng CP, Whitwam T, Boxer LD, Li E, Silberfeld A, Trowbridge S, Mei K, Lin C, Shamah R, Griffith EC, Renthal W, Chen C, Greenberg ME.
bioRxiv
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A NPAS4-NuA4 complex couples synaptic activity to DNA repair.
Authors: Authors: Pollina EA, Gilliam DT, Landau AT, Lin C, Pajarillo N, Davis CP, Harmin DA, Yap EL, Vogel IR, Griffith EC, Nagy MA, Ling E, Duffy EE, Sabatini BL, Weitz CJ, Greenberg ME.
Nature
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Rewiring of human neurodevelopmental gene regulatory programs by human accelerated regions.
Authors: Authors: Girskis KM, Stergachis AB, DeGennaro EM, Doan RN, Qian X, Johnson MB, Wang PP, Sejourne GM, Nagy MA, Pollina EA, Sousa AMM, Shin T, Kenny CJ, Scotellaro JL, Debo BM, Gonzalez DM, Rento LM, Yeh RC, Song JHT, Beaudin M, Fan J, Kharchenko PV, Sestan N, Greenberg ME, Walsh CA.
Neuron
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NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior.
Authors: Authors: Xu P, Berto S, Kulkarni A, Jeong B, Joseph C, Cox KH, Greenberg ME, Kim TK, Konopka G, Takahashi JS.
Neuron
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