Xinyu Zhao

Professor of Neuroscience

xinyu.zhao@wisc.edu

608-263-9906

Neuroscience
Genetics and epigenetic regulation of neural stem cells and neuronal development

Address
T513 Waisman Center
Education
PhD: University of Washington, Seattle, WA (1997), Postdoctoral Research: the Salk Institute for Biological Studies, San Diego, CA
Lab Website
https://zhao-lab.com/
Department
Neuroscience
Research Interests
Genetics and epigenetic regulation of neural stem cells and neuronal development
Research Fields
Development, Gene Expression, Genomics & Proteomics, Human, mouse & rat

Research Description:

The research in our laboratory focuses on understanding the molecular mechanisms that regulate neuronal development. We are particularly interested in two aspects of gene expression regulation: epigenetic mechanisms through chromatin remodeling and noncoding RNAs and post-transcriptional regulation through RNA binding proteins. We use mouse genetics, primary neural stem cells (NSC), and human pluripotent stem cells (hiPSC, hESC), as well as CRISPR gene editing-created genetic mutant and gene-corrected mouse lines and human cells as model systems in our research. We employ a combination of genetic, genomic, proteomic, imaging, and behavioral methods to interrogate the fundamental relationships among gene, brain, and behaviors in neuronal development and their implications in human neurodevelopmental disorders, such as Fragile X Syndrome,  Autism, and Rett syndrome.


Representative Publications:

Reducing histone acetylation rescues cognitive deficits in a mouse model of Fragile X syndrome. Li Y, Stockton ME, Eisinger BE, Zhao Y, Miller JL, Bhuiyan I, Gao Y, Wu Z, Peng J, Zhao X.

Nat Commun. 2018 Jun 27;9(1):2494. doi: 10.1038/s41467-018-04869-3. PMID:29950602 (news: https://news.wisc.edu/study-points-researchers-toward-new-therapies-for-fragile-x-syndrome/)

Jobe EM*, Yu Gao Y* (*equal contribution) Eisinger BE, Mladucky JK, Giuliani CC, Kelnhofer LE, and Zhao X. Methyl-CpG binding protein MBD1 regulates neuronal lineage commitment through maintaining adult neural stem cell identity. J. Neurosci. 2017; 37(3):523-536 PMID:27920144

Gao Y, Wang F,  Eisinger BE, Kelnhofer LE., Jobe E, and Zhao X. Integrative Single-Cell Transcriptomics Reveal Molecular Networks Defining Neuronal Maturation during Postnatal Neurogenesis. 2016 Cerebral Cortex PMID: 26989163

Li Y, Stockton ME, IBhuiyan 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)

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, PMCID: PMC4472556. Publ.ID: CELREP1788

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); 112(36):E4995-5004. PMID: 26305964 PMCID: PMC4568658

Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, Murthy AC, Goggin SL, Eisch AJ, Oostra BA, Nelson DL, Jin P, Zhao X. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat Med. 2011 May;17(5):559-65. PubMed PMID: 21516088; PubMed Central PMCID: PMC3140952.

Gao Y, Wang F,  Eisinger BE, Kelnhofer LE., Jobe E, and Zhao X. Integrative Single-Cell Transcriptomics Reveal Molecular Networks Defining Neuronal Maturation during Postnatal Neurogenesis. 2016 Cerebral Cortex PMID: 26989163

Li Y, Stockton ME, IBhuiyan 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)

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, PMCID: PMC4472556. Publ.ID: CELREP1788

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); 112(36):E4995-5004. PMID: 26305964 PMCID: PMC4568658

Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, Murthy AC, Goggin SL, Eisch AJ, Oostra BA, Nelson DL, Jin P, Zhao X. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat Med. 2011 May;17(5):559-65. PubMed PMID: 21516088; PubMed Central PMCID: PMC3140952.