Ph.D., 1997, University of Washington, Seattle
(608) 263-9906 Office
(608) 263-6745 Lab
Postdoctoral Fellow (click here)
(accepting rotation students during spring 2012.
Plan to accept one or two PhD students for dissertation research)
Molecular mechanisms that regulate neural stem cells and neurodevelopment
The research in our laboratory focuses on understanding the molecular mechanisms that
regulate neural stem cells and neurodevelopment with the goal of applying this knowledge
in the treatment of neurological disorders and injuries
Stem cells have two fundamental properties: self-renewal and multipotency.
During development, stem cells and resulting progenitor cells are responsible for generating all
the tissues and cells of an organism. In the adult, stem cells exist in many tissues throughout
life and may play critical roles in physiological functions and tissue regeneration.
The maintenance of their "stemness" state and commitment to differentiation are tightly controlled by
both intrinsic genetic and epigenetic programs and extrinsic stimuli.
Neural stem cells in the postnatal
brain have significant roles in both normal brain functions, such as and learning, memory and the brain's
response to injuries. We are investigating the mechanisms governing the behaviors and functions of neural stem cells in both healthy conditions and in neurological diseases.
Epigenetic mechanisms, including DNA methylation,
chromatin remodeling, and noncoding RNAs have profound regulatory roles in controlling mammalian gene expression.
Disturbance of these interacting systems can lead to inappropriate expression or silencing of genes,
causing an array of multi-system disorders. A main focus of our research is
to understand the epigenetic basis of cell fate specification and neurodevelopment.
Neurodevelopmental disorders are highly
heterogeneous constellation of disorders, both in terms of etiology and clinical manifestations.
Using neural stem cells as model systems, we are investigating the molecular mechanisms that regulate
postnatal neuronal development during postnatal period and their implications in human neurodevelopmental disorders such as Rett Syndrome, Autism, and Fragile X syndrome.
Selected Publications (Additional Publications - click here)
- Guo W, Zhang L , Christopher DM, Teng Z, Fausett SR, Klingensmith K, Jin P, and Zhao X. RNA-binding Protein FXR2 Regulates Proliferation and Differentiation of Adult Hippocampal Neural Stem Cells by Reducing Noggin Expression Neuron 2011. 70 (5): 924-938
- Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, Murthy A, Goggin SL, Eisch AJ, Oostra BA, Nelson DL, Jin P, and Zhao X. Selective deletion of FMRP in adult neural stem cells disrupts hippocampal neurogenesis and learning Nature Medicine 17(5):559-65. PMID: 21516088. (Cover story. Featured by Faculty1000 as top 2% of published articles in biology and medicine.).
- Smrt RD, Pfeiffer RL, and Zhao X. Age-Dependent Expression of Mecp2 in a Novel Heterozygous Mosaic Mouse Model. Hum. Mol. Genet. 2011. PMID: 21330301
- Smrt RD, Szulwach KE Pfeiffer RL, Li X, Guo W, Pathania M, Teng Z, Luo Y, Peng J, Wilson MC, 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):1060-70. PMID: 20506192.
- Liu C, Teng Z, Santistevan NJ, Szulwach KE, 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):433-44. PMID: 20452318.
- Szulwach KE, Li X, Smrt RD, Li Y, Luo Y, Li L, Lin L, Santistevan NJ, Li W, Zhao X#., and Jin P# (#, co-corresponding authors). Cross talk between microRNA and epigenetic regulation in adult neurogenesis J. Cell Biol., 2010 189 (1) 127-41. PMC Journal - In Process
- Luo Y, Shan G, Guo W, Smrt RD, Johnson EB, Li X, Pfeiffer RL, Szulwach KE, Duan R, Barkho BZ, 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
- Barkho BZ, Munoz A, Li X, Li L, Cunningham LA, and Zhao X. (2008) Endogenous Matrix Metalloproteinase (MMP)-3 and MMP-9 Promote the Differentiation and Migration of Adult Neural Progenitor Cells in Response to Chemokines. Stem Cells. 26(12):3139-49.
- Allan AM, Liang X, Luo,Y, Pak C, LI, X, Szulwach KE, Chen D, Jin P, and Zhao X. The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits 2008 Hum. Mol. Genet. 2008 17(13):2047-57. PMCID: PMC2700628
- Li X., Barkho BZ, Luo Y, Smrt RD, Liu C, Kuwabara T, Gage FH, and Zhao X. Epigenetic regulation of stem cell mitogen FGF-2 by Mbd1 in adult neural stem/progenitor cells. J. Biol. Chem. 2008. 283(41):27644-52. PMCID: PMC2562066
- Smrt, RD. Eaves-Angenes J, Barkho BZ, Santistevan NJ, Aimone JB, Zhao C, Gage FH, and Zhao X. Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol. of Diseases 2007 27 (1):77-89. (Journal cover image)
Additional Publications (click here)
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