Photo of Michael E. Greenberg,  PhD

Michael E. Greenberg, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-2510
Fax: (617) 432-3223


meg@hms.harvard.edu

Michael E. Greenberg, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Nathan Marsh Pusey Professor of Neurobiology, Neurobiology, Harvard Medical School
  • Professor, Neurology, Harvard Medical School
  • Chair, Neurobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research is directed towards understanding the mechanisms by which environmental stimuli including neurotrophins and neural activity elicit cellular responses in the developing and mature nervous system. Using mouse models and genome-wide screening technologies, our experiments have identified signal transduction pathways that mediate various processes during the development of the nervous system including cell fate determination and cell type specification, cell survival and death, axon and dendritic outgrowth, and synapse formation and refinement. As each of these steps is critical for the correct wiring and function of the mammalian brain, we are particularly interested in those proteins that, when mutated, lead to diseases such as cancer and disorders of cognitive function.

Publications

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  • Robichaux MA, Chenaux G, Ho HH, Soskis MJ, Greenberg ME, Henkemeyer M, Cowan CW. EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. Dev Neurobiol 2015. PubMed
  • Andzelm MM, Cherry TJ, Harmin DA, Boeke AC, Lee C, Hemberg M, Pawlyk B, Malik AN, Flavell SW, Sandberg MA, Raviola E, Greenberg ME. MEF2D Drives Photoreceptor Development through a Genome-wide Competition for Tissue-Specific Enhancers. Neuron 2015; 86:247-263. PubMed
  • Eisner A, Pazyra-Murphy MF, Durresi E, Zhou P, Zhao X, Chadwick EC, Xu PX, Hillman RT, Scott MP, Greenberg ME, Segal RA. The Eya1 Phosphatase Promotes Shh Signaling during Hindbrain Development and Oncogenesis. Dev Cell 2015; 33:22-35. PubMed
  • Gabel HW, Kinde B, Stroud H, Gilbert CS, Harmin DA, Kastan NR, Hemberg M, Ebert DH, Greenberg ME. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature 2015. PubMed
  • Kinde B, Gabel HW, Gilbert CS, Griffith EC, Greenberg ME. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2. Proc Natl Acad Sci U S A 2015. PubMed
  • Malik AN, Vierbuchen T, Hemberg M, Rubin AA, Ling E, Couch CH, Stroud H, Spiegel I, Farh KK, Harmin DA, Greenberg ME. Genome-wide identification and characterization of functional neuronal activity-dependent enhancers. Nat Neurosci 2014; 17:1330-9. PubMed
  • Spiegel I, Mardinly AR, Gabel HW, Bazinet JE, Couch CH, Tzeng CP, Harmin DA, Greenberg ME. Npas4 Regulates Excitatory-Inhibitory Balance within Neural Circuits through Cell-Type-Specific Gene Programs. Cell 2014; 157:1216-29. PubMed
  • Bloodgood BL, Sharma N, Browne HA, Trepman AZ, Greenberg ME. The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 2013; 503:121-5. PubMed
  • Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1留/FNDC5 pathway. Cell Metab 2013; 18:649-59. PubMed
  • Gabel HW, Greenberg ME. Genetics. The maturing brain methylome. Science 2013; 341:626-7. PubMed
  • Soskis MJ, Ho HY, Bloodgood BL, Robichaux MA, Malik AN, Ataman B, Rubin AA, Zieg J, Zhang C, Shokat KM, Sharma N, Cowan CW, Greenberg ME. A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development. Nat Neurosci 2012. PubMed
  • Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature 2010; 465:182-7. PubMed
  • Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, Hu L, Mok SI, Shah A, Savner EM, Tolias C, Corfas R, Chen S, Inquimbert P, Xu Y, McInnes RR, Rice FL, Corfas G, Ma Q, Woolf CJ, Greenberg ME. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 2010; 65:886-98. PubMed
  • Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 2010; 140:704-16. PubMed
  • Cohen S, Greenberg ME. A bird's-eye view of MeCP2 binding. Mol Cell 2010; 37:451-2. PubMed
  • Shi L, Butt B, Ip FC, Dai Y, Jiang L, Yung WH, Greenberg ME, Fu AK, Ip NY. Ephexin1 is required for structural maturation and neurotransmission at the neuromuscular junction. Neuron 2010; 65:204-16. PubMed
  • Bracaglia G, Conca B, Bergo A, Rusconi L, Zhou Z, Greenberg ME, Landsberger N, Soddu S, Kilstrup-Nielsen C. Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis. EMBO Rep. 2009; 10:1327-33. PubMed
  • Greenberg ME, Xu B, Lu B, Hempstead BL. New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 2009; 29:12764-7. PubMed
  • Wood L, Gray NW, Zhou Z, Greenberg ME, Shepherd GM. Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in an RNA interference model of methyl-CpG-binding protein 2 deficiency. J Neurosci 2009; 29:12440-8. PubMed
  • Siegel G,Obernosterer G,Fiore R,Oehmen M,Bicker S,Christensen M,Khudayberdiev S,Leuschner PF,Busch CJ,Kane C,Hubel K,Dekker F,Hedberg C,Rengarajan B,Drepper C,Waldmann H,Kauppinen S,Greenberg ME,Draguhn A,Rehmsmeier M,Martinez J,Schratt GM. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 2009; 11:705-16. PubMed
  • Pazyra-Murphy MF,Hans A,Courchesne SL,Karch C,Cosker KE,Heerssen HM,Watson FL,Kim T,Greenberg ME,Segal RA. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J Neurosci 2009; 29:6700-9. PubMed
  • Fiore R,Khudayberdiev S,Christensen M,Siegel G,Flavell SW,Kim TK,Greenberg ME,Schratt G. Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J 2009; 28:697-710. PubMed
  • Flavell SW,Kim TK,Gray JM,Harmin DA,Hemberg M,Hong EJ,Markenscoff-Papadimitriou E,Bear DM,Greenberg ME. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron 2008; 60:1022-38. PubMed
  • Hong EJ,McCord AE,Greenberg ME. A biological function for the neuronal activity-dependent component of Bdnf transcription in the development of cortical inhibition. Neuron 2008; 60:610-24. PubMed
  • Lin Y,Bloodgood BL,Hauser JL,Lapan AD,Koon AC,Kim TK,Hu LS,Malik AN,Greenberg ME. Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 2008; 455:1198-204. PubMed
  • Greer PL,Greenberg ME. From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 2008; 59:846-60. PubMed
  • Zieg J,Greer PL,Greenberg ME. SnapShot: Ca(2+)-dependent transcription in neurons. Cell 2008; 134:1080-1080.e2. PubMed
  • Singh KK, Park KJ, Hong EJ, Kramer BM, Greenberg ME, Kaplan DR, Miller FD. Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration. Nat Neurosci 2008; 11:649-58. PubMed
  • Cohen S,Zhou Z,Greenberg ME. Medicine. Activating a repressor. Science 2008; 320:1172-3. PubMed
  • Ma YC, Song MR, Park JP, Henry Ho HY, Hu L, Kurtev MV, Zieg J, Ma Q, Pfaff SL, Greenberg ME. Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron 2008; 58:65-77. PubMed
  • Kim DS, Ross SE, Trimarchi JM, Aach J, Greenberg ME, Cepko CL. Identification of molecular markers of bipolar cells in the murine retina. J Comp Neurol 2008; 507:1795-1810. PubMed
  • Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med 2008; 14:144-53. PubMed
  • Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 2007; 27:10912-7. PubMed
  • Zhou P, Porcionatto M, Pilapil M, Chen Y, Choi Y, Tolias KF, Bikoff JB, Hong EJ, Greenberg ME, Segal RA. Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 2007; 55:53-68. PubMed
  • Tolias KF, Bikoff JB, Kane CG, Tolias CS, Hu L, Greenberg ME. The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development. Proc Natl Acad Sci U S A 2007; 104:7265-70. PubMed
  • Paradis S, Harrar DB, Lin Y, Koon AC, Hauser JL, Griffith EC, Zhu L, Brass LF, Chen C, Greenberg ME. An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development. Neuron 2007; 53:217-32. PubMed
  • Fu WY, Chen Y, Sahin M, Zhao XS, Shi L, Bikoff JB, Lai KO, Yung WH, Fu AK, Greenberg ME, Ip NY. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat Neurosci 2006; 10:67-76. PubMed
  • Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, Lin Y, Savner E, Griffith EC, Hu L, Steen JA, Weitz CJ, Greenberg ME. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 2006; 52:255-69. PubMed
  • Marinescu VD, Kohane IS, Kim TK, Harmin DA, Greenberg ME, Riva A. START: an automated tool for serial analysis of chromatin occupancy data. Bioinformatics 2006; 22:999-1001. PubMed
  • Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 2006; 311:1008-12. PubMed
  • Ge W, He F, Kim KJ, Blanchi B, Coskun V, Nguyen L, Wu X, Zhao J, Heng JI, Martinowich K, Tao J, Wu H, Castro D, Sobeih MM, Corfas G, Gleeson JG, Greenberg ME, Guillemot F, Sun YE. Coupling of cell migration with neurogenesis by proneural bHLH factors. Proc Natl Acad Sci U S A 2006; 103:1319-24. PubMed
  • Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME. A brain-specific microRNA regulates dendritic spine development. Nature 2006; 439:283-9. PubMed
  • Sahin M, Greer PL, Lin MZ, Poucher H, Eberhart J, Schmidt S, Wright TM, Shamah SM, O'connell S, Cowan CW, Hu L, Goldberg JL, Debant A, Corfas G, Krull CE, Greenberg ME. Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron 2005; 46:191-204. PubMed
  • Cowan CW, Shao YR, Sahin M, Shamah SM, Lin MZ, Greer PL, Gao S, Griffith EC, Brugge JS, Greenberg ME. Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 2005; 46:205-17. PubMed
  • Tolias KF, Bikoff JB, Burette A, Paradis S, Harrar D, Tavazoie S, Weinberg RJ, Greenberg ME. The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines. Neuron 2005; 45:525-38. PubMed
  • Hong EJ, West AE, Greenberg ME. Transcriptional control of cognitive development. Curr Opin Neurobiol 2005; 15:21-8. PubMed
  • Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A, Tenzen T, Yuk DI, Tsung EF, Cai Z, Alberta JA, Cheng LP, Liu Y, Stenman JM, Valerius MT, Billings N, Kim HA, Greenberg ME, McMahon AP, Rowitch DH, Stiles CD, Ma Q. Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 2004; 306:2255-7. PubMed
  • Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303:2011-5. PubMed
  • Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB, Gygi SP, Korsmeyer SJ. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003; 424:952-6. PubMed
  • Ranger AM, Zha J, Harada H, Datta SR, Danial NN, Gilmore AP, Kutok JL, Le Beau MM, Greenberg ME, Korsmeyer SJ. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 2003; 100:9324-9. PubMed
  • Datta SR, Ranger AM, Lin MZ, Sturgill JF, Ma YC, Cowan CW, Dikkes P, Korsmeyer SJ, Greenberg ME. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev Cell 2002; 3:631-43. PubMed
  • Zhu JW, Field SJ, Gore L, Thompson M, Yang H, Fujiwara Y, Cardiff RD, Greenberg M, Orkin SH, DeGregori J. E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Mol Cell Biol 2001; 21:8547-64. PubMed
  • Shamah SM, Lin MZ, Goldberg JL, Estrach S, Sahin M, Hu L, Bazalakova M, Neve RL, Corfas G, Debant A, Greenberg ME. EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 2001; 105:233-44. PubMed
  • Sun Y, Nadal-Vicens M, Misono S, Lin MZ, Zubiaga A, Hua X, Fan G, Greenberg ME. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 2001; 104:365-76. PubMed
  • Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol 2001; 21:952-65. PubMed
  • Dalva MB, Takasu MA, Lin MZ, Shamah SM, Hu L, Gale NW, Greenberg ME. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 2001; 103:945-56. PubMed
  • Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 2000; 6:41-51. PubMed
  • Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 1999; 286:1358-62. PubMed
  • Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME. Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 1999; 286:785-90. PubMed
  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96:857-68. PubMed
  • Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Bronson RT, Malynn BA, Bryans M, Zhu C, Chaudhuri J, Davidson L, Ferrini R, Stamato T, Orkin SH, Greenberg ME, Alt FW. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 1999; 95:891-902. PubMed
  • Saudou F, Finkbeiner S, Devys D, Greenberg ME. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 1998; 95:55-66. PubMed
  • Brown JR, Nigh E, Lee RJ, Ye H, Thompson MA, Saudou F, Pestell RG, Greenberg ME. Fos family members induce cell cycle entry by activating cyclin D1. Mol Cell Biol 1998; 18:5609-19. PubMed
  • Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 1998; 20:709-26. PubMed
  • Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME. CREB: a major mediator of neuronal neurotrophin responses. Neuron 1997; 19:1031-47. PubMed
  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91:231-41. PubMed
  • Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME. Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science 1997; 278:477-83. PubMed
  • Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997; 275:661-5. PubMed
  • Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 1996; 273:959-63. PubMed
  • Brown JR, Ye H, Bronson RT, Dikkes P, Greenberg ME. A defect in nurturing in mice lacking the immediate early gene fosB. Cell 1996; 86:297-309. PubMed
  • Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin WG, Livingston DM, Orkin SH, Greenberg ME. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 1996; 85:549-61. PubMed
  • Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270:1326-31. PubMed
  • Frank DA, Greenberg ME. CREB: a mediator of long-term memory from mollusks to mammals. Cell 1994; 79:5-8. PubMed
  • Rosen LB, Ginty DD, Weber MJ, Greenberg ME. Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. Neuron 1994; 12:1207-21. PubMed
  • Ginty DD, Kornhauser JM, Thompson MA, Bading H, Mayo KE, Takahashi JS, Greenberg ME. Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science 1993; 260:238-41. PubMed
  • Bading H, Ginty DD, Greenberg ME. Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science 1993; 260:181-6. PubMed
  • Bading H, Greenberg ME. Stimulation of protein tyrosine phosphorylation by NMDA receptor activation. Science 1991; 253:912-4. PubMed
  • Sheng M, Thompson MA, Greenberg ME. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science 1991; 252:1427-30. PubMed
  • Shyu AB, Belasco JG, Greenberg ME. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev 1991; 5:221-31. PubMed
  • Sheng M, McFadden G, Greenberg ME. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron 1990; 4:571-82. PubMed
  • Rivera VM, Sheng M, Greenberg ME. The inner core of the serum response element mediates both the rapid induction and subsequent repression of c-fos transcription following serum stimulation. Genes Dev 1990; 4:255-68. PubMed
  • Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988; 55:917-24. PubMed
  • Greenberg ME, Ziff EB, Greene LA. Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 1986; 234:80-3. PubMed
  • Greenberg ME, Ziff EB. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 1984; 311:433-8. PubMed
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