Ph.D. University of Pennsylvania School of Medicine, 2000
Postdoctoral Research: Whitehead Institute, Cambridge, MA
Address: 657 Waisman Center
Research InterestsDNA methylation-dependent epigenetic regulation of brain functions
Research FieldsDisease Biology
Neuro & Behavioral Genetics
Human, mouse & rat
Research in my laboratory is aimed at
understanding the molecular mechanism of Rett syndrome, an autistic
spectrum developmental disorder, and DNA methylation dependent
epigenetic regulation of mammalian brain development and function.
Rett syndrome is caused by mutations in the X-linked MECP2 (methyl CpG binding protein 2). The devastating disease has an estimated prevalence of 1 in 10,000-15,000 girls, and is the second most common cause of mental retardation in females. MeCP2 plays a central role in interpreting the epigenetic code of DNA methylation and regulating chromatin remodeling and gene transcription in the mouse brain.
We employ mouse genetics, electrophysiological, and molecular approaches to:
1) Identify MeCP2 target genes.
2) Elucidate the mechanisms by which MeCP2 dynamically regulate the expression of these genes.
3) Characterize the in vivo roles of these genes in the context of RTT and normal brain development.
Zhong, X., Li, H., and Chang,
Q. (2012) MeCP2 phosphorylation is required for modulating synaptic
scaling through mGluR5. Journal of Neuroscience, 32(37):12841-12847.
Li H, Zhong X, Chau KF, Williams EC, Chang Q. (2011) Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory. Nat Neurosci. 2011 Jul 17;14(8):1001-8.
Chang, Q., Khare, G.D., Dani, V.S., Nelson, S.B., and Jaenisch, R. (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49(3):341-348.
Dani, V.S.*, Chang, Q.*, Maffei, A., Turrigiano, G.G., Jaenisch, R., and Nelson, S.B. (2005) Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett Syndrome. PNAS 102(35):12560-12565. (* Equal contribution)
Chen, W.G., Chang, Q., Lin, Y., Meissner, A., West, A.E., Griffith, E.C., Jaenisch, R., and Greenberg, M.E. (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302:885-889.