We use various forms of gene targeting in mouse embryonic stem cells to generate genetically engineered mouse lines. One major focus of our lab is to use these mutant mice as animal models for human diseases, which allows us to study the molecular mechanism of diseases in vivo. In addition, we are beginning to explore the role of DNA methylation-dependent epigenetic regulatory mechanism in adult neurogenesis. Most recently, we have generated disease-specific induced pluripotent stem (iPS) cells from several Rett syndrome (RTT) patients. We plan to use these RTT iPS cells as a tissue culture based human model of the disease for understanding its pathogenesis and screening for drugs.
- Li, H., Zhong, X., Chau, K.F., Williams, E.S., and Chang, Q. (2011) Loss of Activity-Induced Phosphorylation of MeCP2 Enhances Synaptogenesis, LTP, and Spatial Memory. Nature Neuroscience 14(8):1001-8. PMCID: PMC3273496
- Ananiev, G., Williams, E.C., Li, H., and Chang, Q. (2011) Isogenic Pairs of Wild Type and Mutant Induced Pluripotent Stem Cell (iPSC) Lines from Rett Syndrome Patients as In Vitro Disease Model. PloS ONE 6(9):e25255. Epub 2011 Sep 26. PMCID: PMC3180386
- Johnson, R.A., Lam, M., Punzo, A.M., Li, H., Lin, B.R., Ye, K., Mitchell, G.S., and Chang, Q. (2012) 7,8-dihydroxyflavone (7,8-DHF) exhibits therapeutic efficacy in a mouse model of Rett syndrome. Journal of Applied Physiology Epub 2011 Dec 22
- Williams, E.C., Zhong, X., Mohamed, A., Li, R., Liu, Y., Dong, Q., Ananiev, G.E., Mok, J.C., Lin, B.R., Lu, J., Chiao, C., Cherney, R., Li, H., Zhang, S.C., and Chang, Q. (2014) Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum Mol Genet. 2014 Jun 1;23(11):2968-80. doi: 10.1093/hmg/ddu008. Epub 2014 Jan 12.
- Li R, Dong Q, Yuan X, Zeng X, Gao Y, Chiao C, Li H, Zhao X, Keles S, Wang Z, Chang Q. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome. PLoS Genet. 2016 Jun 28;12(6):e1006129. doi: 10.1371/journal.pgen.1006129. eCollection 2016 Jun.