Xinyu Zhao, PhD
Position title: Professor, Neuroscience
T513 Waisman Center
1500 Highland Ave
- Lab Website
- Zhao Lab
The molecular mechanisms that regulate neural stem cells and neurodevelopment with the goal of applying this knowledge in the treatment of neurodevelopmental disorders.
Stem cells are responsible for generating all the tissues and cells of an organism during development. In adult mammals, stem cells exist in many tissues throughout life and play critical roles in physiological functions and tissue regeneration. Neural stem cells 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 of stem cells: epigenetic mechanisms and post-transcriptional regulation. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and noncoding RNAs, 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 regulations are mediated by complex mechanisms, including noncoding RNAs such as microRNAs and RNA-binding proteins (e.g. FMRP, FXR1P, FXR2P). Many of these regulators are important for human brain development.
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.
- Gao Y, Shen M, Dong Q, Kannan S, Hoang J, Eisinger BE, Javadi S, Chang Q, Wang D, and Zhao X. RGS6 mediates effects of voluntary running on adult hippocampal neurogenesis. Cell Reports 2020 Aug 4 2020; DOI:https://doi.org/10.1016/j.celrep.2020.107997
- Li M, Shin J, Risgaard RD, Parries MJ, Wang J, Chasman DA, Liu S, Roy S, Bhattacharyya A, and Zhao X. Identification of FMRP regulated molecular networks in human neurodevelopment. Genome Res.2020 Mar 16. doi: 10.1101/gr.251405.119. [Epub ahead of print]
- Shen M, Wang F, Li M, Sah N., Stockton ME, Tidei JJ, Gao Y, Korabelnikov T, Kannan S, Vevea JD, Chapman ER, Bhattacharyya A, and Zhao X. Reduced mitochondrial fusion and Huntingtin levels contribute to impaired dendritic maturation and behavioral deficits in Fmr1 mutant mice. 2019 Nature Neuroscience 22(3):386-400. (Recommended by Faculty 1000)
- 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 Comm. 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/)
- Patzlaff NE, Nemec KM, Malone SG, Li Y, Zhao X. Fragile X related protein 1 (FXR1P) regulates proliferation of adult neural stem cells. Hum Mol Genet. 2017 Apr 1;26(7):1340-1352. doi: 10.1093/hmg/ddx034.PMID: 28204491
- 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)
- 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, 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, 2011. 17(5):559-65. PMID: 21516088. (Cover story. Featured by Faculty1000 as top 2% of published articles in biology and medicine.).
- Liu C, Teng Z, Santistevan NJ, Szulwach KE, Guo W, Jin P, and Zhao X. “Epigenetic regulation of miR-184 by Mbd1 governs neural stem cell proliferation and differentiation,” Cell Stem Cell, 2010. 6(5):433-44. PMID: 20452318.