Professor - Ph.D., 1997, University of Washington, Seattle
Office: (608) 263-9906 | Lab: (608) 890-4392
RESEARCH INTERESTS - Transcriptional and post-transcriptional mechanisms regulating neural stem cells and brain development
(Please contact Dr. Zhao)
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 are the stem cells of the central nervous system and have the capacity to differentiate into different types of neurons and glia. In the postnatal and adult brains neural stem cells have significant roles in both normal brain functions, such as and learning, memory and the brain’s response to injuries.
My laboratory investigates transcriptional and post-transcriptional mechanisms that regulate mammalian neural stem cells and neuronal development. We use mouse genetics, primary neural stem cells, and human patient-derived pluripotent stem cells as model systems in our research. We employ a combination of genetic, genomic, proteomic, imaging, and behavioral methods to interrogate the roles of genes, epigenetic regulators, RNAs in neuronal development and their implications in human neurodevelopmental disorders, including Rett Syndrome, Autism, and Fragile X syndrome, etc.
Selected Publications (Additional Publications – click here)
- Li M, Zhao H, Ananiev, GE, Musser M, Ness K, Maglaque D, Saha K, Bhattacharyya, A*., and Zhao, X* (*, co-correspondence). Establishment of reporter lines for detecting fragile X mental retardation (FMR1) gene reactivation in human neural cells. 2016 Stem Cells (in press)
- Li Y, Stockton ME, Bhuiyan I, Eisinger BE, Yu Gao Y, Bhattacharyya A, and Zhao X. MDM2 Inhibition rescues neurogenic and cognitive deficits in fragile X mice Science Translational Medicine April 27 2016. (see news release April 27, 2016)
- Gao Y*, Wang F*, Eisinger BE*, Kelnhofer LE, Jobe EM, Zhao X. “Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation during Postnatal Neurogenesis.” Cerebral Cortex. (2016, March 17). *contributed equally. (see News release March 17, 2016)
- Wang F, Tidei JJ, Polich ED, Gao Y, Zhao H, Perrone-Bizzozero NI, Weixiang Guo , Zhao X. Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis. Proc Natl Acad Sci U S A plus (2015)
- Guo W, Polich ED, Juan Su, J, Gao Y, Christopher, DM, Allan AM, Wang M, Wang F, Wang G, Zhao X. Fragile X Proteins FMRP and FXR2P control synaptic GluA1 expression and neuronal maturation via distinct mechanisms. Cell Reports. 2015. NIHMS690530, Publ.ID: CELREP1788
- Gao Y, Su J, Guo W, Polich ED, Magyar DP, Xing Y, Li H, Smrt RD, Chang Q, Zhao X. Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons. Stem Cells. 2015 May;33(5):1618-29. PubMed PMID: 25639236; PubMed Central PMCID: PMC4409556
- 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
- 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