My lab is focused on two projects:Research in my lab is focused on regulation of gene expression by specific transcription factors during brain development, the implication of their loss on brain function and the mechanism(s) underlying the manifestation of neurological disorders. Specifically, my lab is interested in the molecular and cellular mechanism underlying Rett syndrome and other autism spectrum disorders. RTT is caused by sporadic mutations in the methyl-CpG binding protein 2 gene, Mecp2. Although MeCP2 is a global transcription factor, its loss affects preferentially the central nervous system (CNS). My lab studies the molecular mechanism(s) by which the loss of MeCP2functionmanifest as neurological symptoms at specific developmental stage, and the non-cell autonomous effect of glia in manifestation and rescue of RTT. The other research interest of my lab focuses on identifying the roles of the transcriptional repressor REST in CNS development in health and disease. REST is a master regulator of a large network of genes involved in acquisition of neural fate and its dysregulation has been implicated in several neurological disorders, as well as cancer. My lab characterizes the roles of the REST repressor complex in maintaining stem cell identity and progressing into different neural lineages in vivo and ex-vivo. Both projects involve multidisciplinary approaches including molecular, cellular and behavioral approaches.
1. 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.
2. 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.
3. Ballas, N. and Mandel, G. (2005) The many faces of REST oversee epigenetic epigenetic programming of neuronal genes. Curr. Opin. Neurobiol. 15, 500-506.
4. Ballas, N., Lioy, D.T., Grunseich, C., 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.
5. Lioy, D. T., Monaghan, C., Hirrlinger, F.K., Bissonnete, J.M., Ballas, N., and Mandel, G. (2011) A role for glia in progression of Rett’s Syndrome. Nature, 475, 497-500.
6. Mandel, G., Fiondella, C., Covey, M., Lu, D.D., LoTurco, J.J., and Ballas, N.(2011) REST controls radial migration and temporal neuronal specification during nervous system development. Proc. Natl. Acad. Sci. USA, 108, 16789-96794.
7. Covey, M.V., Streb, J., Spektor, R., and Ballas, N. (2012)REST regulates the pool size of the different neural lineages by restricting the generation of neurons and oligodendrocytes from neural stem/progenitor cells. Development, 139, 2878-2890.
8. Nguyen, M.V., Du, F., Felice, C.A., Nigam, A., Mandel, G., Robinson,J.K., and Ballas, N. (2012)MeCP2 is critical for maintaining the mature neuronal networks and global brain anatomy during late stages of postnatal brain development. J. Neurosci. 32, 10021-10034.
9. Nguyen, M.V., Felice, C.A., Du, F., Covey, M.V., Robinson,J.K., Mandel, G., and Ballas, N. (2013) Oligodendrocyte lineage cells contribute unique features to Rett Syndrome neuropathology. J. Neurosci. 33, 18764-18774.
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