Genetics and epigenetic regulation of neural stem cells and neuronal development
- T513 Waisman Center
- PhD: University of Washington, Seattle, WA (1997), Postdoctoral Research: the Salk Institute for Biological Studies, San Diego, CA
- Lab Website
- Research Interests
- Genetics and epigenetic regulation of neural stem cells and neuronal development
- Research Fields
- Development, Gene Expression, Genomics & Proteomics, Human, mouse & rat
The research in our laboratory focuses on understanding the molecular mechanisms, such as epigenetic regulation and post-transcriptional gene regulation, that control neural stem cells and neurodevelopment with the goal to apply this knowledge in treating brain disorders.
During development, stem cells are responsible for generating all the tissues and cells of an organism. In adult, stem cells exist in many tissues throughout life and may play critical roles in physiological functions and tissue regeneration. Neural stem cells in the postnatal brains could have significant roles in normal brain functions, such as learning and memory and brain’s response to injuries. We are interested in two aspects of gene expression regulation: epigenetic mechanisms and post-transcriptional gene regulation. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Disturbance of these interacting systems can lead to inappropriate expression or silencing of genes, causing an array of multi-system disorders. Post-transcriptional gene regulation are mediated by complex mechanisms, including noncoding RNAs such as microRNAs and RNA-binding proteins, such as FMRP. Many of these regulators are important for human brain development.
We use genetic modified mice and primary neural stem cells as model systems and a combination of molecular, cellular, imaging, and behavioral techniques investigate the molecular mechanisms that regulate postnatal neuronal development and its implication in human neurodevelopmental disorders, such as Rett Syndrome, Autism, and Fragile X syndrome.
For full list of publications, go to this link: http://neuro.wisc.edu/faculty/zhao.asp
Luo, Y., Shan, G., Guo, W., Smrt, R. D., Johnson, E. B., Li, X., Pfeiffer, R. L., Szulwach, K. E., Duan, R., Barkho, B. Z., Li, W., Liu, C., Jin, P. and Zhao, X. (2010). “Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.” PLoS genetics 6(4): e1000898. PMID: 20386739; PMCID: PMC2851565
Liu, C., Teng, Z. Q., Santistevan, N. J., Szulwach, K. E., Guo, W., Jin, P. and Zhao, X. (2010). “Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation.” Cell stem cell 6(5): 433-444. PMID: 20452318; PMCID: PMC2867837
Smrt, R. D., Szulwach, K. E., Pfeiffer, R. L., Li, X., Guo, W., Pathania, M., Teng, Z. Q., Luo, Y., Peng, J., Bordey, A., Jin, P. and Zhao, X. (2010). “MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1.” Stem Cells 28(6): 1060-1070. PMID: 20506192
Allan, A. M., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K. E., Chen, D., Jin, P. and Zhao, X. (2008). “The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits.” Hum Mol Genet 17(13): 2047-2057.
Guo, W., Allan, A. M., Zong, R., Zhang, L., Johnson, E. B., Schaller, E. G., Murthy, A. C., Goggin, S. L., Eisch, A. J., Oostra, B. A., Nelson, D. L., Jin, P. and Zhao, X. (2011). “Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning.” Nature Medicine 17(5): 559-565. PMID: 21516088. (Cover story. Featured by Faculty1000 as top 2% of published articles in biology and medicine.)
Guo, W., Zhang, L., Christopher, D. M., Teng, Z. Q., Fausett, S. R., Liu, C., George, O. L., Klingensmith, J., Jin, P. and Zhao, X. (2011). “RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression.” Neuron 70(5): 924-938.
Guo W., Murthy A.C., Zhang L., Johnson, E.B., Schaller, E, G., Allan A.M., and Zhao X. Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome. (2011) Hum. Mol. GenetPMID: 22048960. PMC Journal – In Process