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Faculty

Nurit Ballas, Ph.D.
Research Professor
Department of Biochemistry and Cell Biology

Life Sciences Building
Stony Brook University
Stony Brook, NY 11794-5215

Office telephone: 631-632-1572
Fax: 631-632-8575

E-mail: nballas@notes.cc.sunysb.edu

     

Research description:

My lab is focused on two projects:

  1. Identifying the roles of the transcriptional repressor REST and its corepressor CoREST throughout neural development. The RE1 silencing transcription factor, REST, is a master regulator of a large network of genes involved in acquisition of neural fate, including neuronal, proneural, and brain specific microRNA genes. We showed that REST, and its corepressor CoREST, play important roles in mediating repression and chromatin plasticity in stem cells. In addition, our data show that REST is regulated differentially during different stages of neural development, pointing to the significance of regulation of REST itself in maintaining and progressing to different lineages. Our research aims to identify the roles of REST and CoREST in maintaining stem cell identity and progressing into different neural lineages, using gain- and loss-of-function approaches, in vitro and in vivo. Our recent studies show that the regulated expression of REST is critical for the spatio-temporal transition of neural stem/progenitor cells to neurons during nervous system development suggesting that REST acts as a timer of neural differentiation during nervous system development.

  2. Analyzing the molecular mechanism(s) underlying the neurodevelopmental disorder Rett Syndrome (RTT). RTT is a post-natal neurodevelopmental disorder that strikes girls during early childhood. Girls born with RTT attain normal developmental milestones for 6–18 months, after which they begin to regress, losing speech, motor skills, and purposeful hand motions. They also suffer many other problems including microcephaly, mental retardation, autism, severe respiratory distress, epileptic seizures, and overall retarded growth. MeCP2 mutations in boys usually lead to neonatal encephalopathy and death during the first year of life. Patients afflicted with the neurodevelopmental disorder Rett Syndrome (RTT) have mutations in the X-linked gene encoding the methyl-CpG binding protein 2, MeCP2. Why mutations in MeCP2 cause RTT, and why the central nervous system preferentially is affected, is unknown. Previous studies have focused on MeCP2 function in neurons because of the prevailing view that glia do not express MeCP2. We found not only that glia express MeCP2, but cultured astroglia isolated from MeCP2-deficient (RTT) mice, or their conditioned medium, confer aberrant morphology on wild type (WT) neurons that is similar to that seen in human patients. Currently, we are generating mouse models in which MeCP2 is depleted or reactivated in specific glial types in normal mice or RTT mouse models respectively.

Related publications:

  • Ballas, N., Battaglioli, E., Atouf, F., Andres, M.E., Chenoweth, J., Anderson, M.E., Burger, C., Moniwa, M., Davie, J.R., Bowers, W.J., Federoff, H.J., Rose D., Rosenfeld M. G., Brehm P., and Mandel, G. (2001) Regulation of neuronal traits by a novel transcriptional complex. Neuron 31, 353-365.
  • Ballas, N., Grunseich, C., Lu, D.D., Speh, J.C., and Mandel, G. (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121, 645-657.
  • Ballas, N. and Mandel, G. (2005) The many faces of REST oversee epigenetic epigenetic programming of neuronal genes. Curr. Opin. Neurobiol. 15, 500-506.
  • Ballas, N., Grunseich, C., Lioy, D., and Mandel, G. (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology: a cellular model for Rett Syndrome. Nat. Neurosci. 12, 311-317.
  • Lioy, D. T., Monaghan, C., Hirrlinger, F.K., Bissonnete, J.M., Ballas, N., and Mandel, G. (2010) Re-expression of MeCP2 in astrocytes rescues neurological symptoms in a mouse model of Rett Syndrome. Nature In revision.
  • Mandel, G., Fiondella, C.G., Covey, M., Lu, D.D., LoTurco, J.J., Ballas, N. (2010)
    REST regulates the spatio-temporal transition of neural stem/progenitor cells to neurons during nervous system development. Neuron In submission.

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