Xinyu Zhao

Research Description:

The research in our laboratory focuses on understanding the molecular mechanisms that regulate neural stem cells and neuronal development, with the goal of developing better treatment for neurodevelopmental and neurological disorders.

We use transgenic mice, human pluripotent stem cells (iPSCs, ESCs), patient-derived and CRISPR gene-edited stem cells, and 3D forebrain organoids, as model systems. We employ cutting edge single-cell and cell type-specific -omics (e.g. single cell/single nucleus RNA-seq/ATAC-seq, Patch-seq, RiboTag-seq, TRAP-seq, proteomics, etc), fluorescent imaging, and behavioral methods to interrogate the roles of genes, epigenetic regulators, RNAs, and proteins in neuronal development. We determine how the mutations of these regulators may contribute to brain disorders and identify potential therapeutic targets and treatment methods.

Representative Publications:

Search publications by Xinyu Zhao

Guo Y, Shen M, Dong Q, Mendez-Albelo NM$, Le J%, Li M, Huang SX%, Jarzembowski ED%, Schoeller KA%, Stockton ME%, Sirois CL, Horner VL, Sousa AMM, Gao Y, Birth Defects Research Laboratory, Levine JE, Wang D, Chang Q, Zhao, X. “Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway” Nature Communications June 26 202

Shen M, Guo Y, Dong Q, Gao, Y, Stockton ME%, Li M, Kannan S%, Korabelnikov T%, Schoeller, AK%, Sioris CL, Zhou C$, Le J%, Chang C, Sun, Q-Q, Wang D, and Zhao X. FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors. Mol Psychiatry 2021 Apr 16. doi: 10.1038/s41380-021-01096-z. PMID: 33863995

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 Research (here). 2020 Mar 16. doi: 10.1101/gr.251405.119. see a news release on this paper.

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. Nature Neuroscience (2019)

Li Y., Stockton ME%, Eisinger BE, Zhao Y, Miller JL%, Bhuiyan I.%, Gao Y, Wu Z, Peng J, and Zhao X, Reducing histone acetylation rescues cognitive deficits in a mouse model of Fragile X syndrome. 2018 Nature Communications 9, 2494. June 27 2018

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

Guo W, Zhang L, Christopher DM%, Teng ZQ, Fausett SR, Liu C, George OL, Klingensmith J, Jin P, and Zhao X. RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression. Neuron. 2011 Jun 9;70(5): 924-938. PMID: 21658585; PMCID: PMC313766.

Guo, W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG%, Murthy AC%, Goggin SL%, Eisch AJ, Oostra BA, Nelson DL, Jin P and Zhao X. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nature Medicine. 2011 May; 17(5): 559-565.

Liu C*, Teng Z* (*equal contribution), 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. PMCID: PMC2867837.