Description: C:\Yan G3\ZY-Web\zhen_yan.jpg               Zhen Yan, Ph.D.

             SUNY Distinguished Professor

Department of Physiology and Biophysics

School of Medicine & Biomedical Sciences

State University of New York at Buffalo


Research Interests:  

Synaptic Mechanisms of Mental Health and Disorders

Our research goal is to understand the synaptic mechanisms commonly involved in the pathophysiology of a variety of brain disorders, including autism, schizophrenia, depression, and Alzheimer's disease. Specifically, we investigate the synaptic action of various neuromodulators that are linked to mental illnesses, including disease susceptibility genes, stress hormones and monoamines (dopamine and serotonin). We try to understand how these neuromodulators regulate glutamatergic and GABAergic transmission in prefrontal cortex (PFC), which is important for cognitive and emotional control under normal conditions. We also try to understand how the aberrant action of neuromodulators under pathological conditions leads to dysregulation of synaptic transmission in PFC.


Animal models of diseases and human stem cell-derived neurons are used in our studies. The major techniques include: whole-cell patch-clamp recordings of synaptic currents, viral-based in vivo gene transfer, biochemical and immunocytochemical detection of synaptic proteins, molecular analysis of genetic and epigenetic alterations, chemogenetic manipulation of neuronal circuits, and behavioral assays. By integrating the multidisciplinary approaches, we have revealed the unique and convergent actions of neuromodulators on postsynaptic glutamate and GABAA receptors, and their contributions to the manifestation of behavioral deficits in disease states.

Contact Information:

Tel:                                (716) 829-3058 (office), (716) 829-3592 (lab)
Lab location:                  955 Main St. Rm. 3150

Office location:              955 Main St. Rm. 3156  

Mailing address:            955 Main St. Rm. 3102, Buffalo, NY 14203


Recent Selective Peer-Reviewed Publications:  



*       Zheng Y, Liu A, Wang ZJ, Cao Q, Wang W, Lin L, Ma K, Zhang F, Wei J, Matas E, Cheng J, Chen GJ, Wang X, Yan Z (2019) Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer's disease. Brain 142:787-807. [PDF file] *Reported in New York Post, England's Daily Mail, EurekAlert!(AAAS), etc.

*       Lin L, Liu A, Li HQ, Feng J, Yan Z (2019) Inhibition of histone methyltransferases EHMT1/2 reverses b amyloid-induced loss of AMPAR currents in human stem cell-derived cortical neurons. J. Alzheimer's Disease (in press).

*       Wang ZJ, Zhong P, Ma K, Seo JS, Yang F, Hu Z, Zhang F, Lin L, Wang J, Liu T, Matas E, Greengard P, Yan Z (2019) Amelioration of autism-like social deficits by targeting histone methyltransferases EHMT1/2 in Shank3-deficient mice. Mol. Psychiatry (in press). [PDF file]

*       Jin J, Bhatti DL, Lee KW, Medrihan L, Cheng J, Wei J, Zhong P, Yan Z, Kooiker C, Song C, Ahn JH, Obermair GJ, Lee A, Gresack J, Greengard P, Kim Y (2019) Ahnak scaffolds p11/Anxa2 complex and L-type voltage-gated calcium channel and modulates depressive behavior. Mol. Psychiatry (in press). [PDF file]

*       Qin L, Ma K, Yan Z (2019) Chemogenetic activation of prefrontal cortex in Shank3-deficient mice ameliorates social deficits, NMDAR hypofunction and Sgk2 downregulation. iScience 17:24-35. [PDF file]

*       Zhu BL, Long Y, Luo W, Yan Z, Lai YJ, Zhao LG, Zhou WH, Wang YJ, Shen LL, Liu L, Deng XJ, Wang XF, Sun F, Chen GJ (2019) MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation. Brain 142:176-192. [PDF file]

*       Xiang XJ, Song L, Deng XJ, Tang Y, Min Z, Luo B, Wen QX, Li KY, Chen J, Ma YL, Zhu BL, Yan Z, Chen GJ (2019) Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology. Exp Neurol. (in press) Epub ahead of print. [PDF file]

*       Lai YJ, Zhu BL, Sun F, Luo D, Ma YL, Luo B, Tang J, Xiong MJ, Liu L, Long Y, Hu XT, He L, Deng XJ, Zhang JH, Yang J, Yan Z, Chen GJ (2019) Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice. Aging Cell e12961 Epub ahead of print. [PDF file]



*       Qin L, Ma K, Wang ZJ, Hu Z, Matas E, Wei J, Yan Z (2018) Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition. Nature Neurosci. 21:564-575. [PDF file] [supplemental materials] *Featured in Science Translational Medicine, Reported in England's Daily Mail, Pharmaceutical Technology, etc.

*       Tan T, Wang W, Williams J, Ma K, Cao Q, Yan Z (2018) Stress exposure in dopamine D4 receptor knockout mice induces schizophrenia-like behaviors via disruption of GABAergic transmission. Schizophrenia Bulletin (in press) Epub ahead of print. [PDF file]

*       Ma K, Qin L, Matas M, Duffney LJ, Liu A, Yan Z (2018) Histone deacetylase inhibitor MS-275 restores social and synaptic function in a Shank3-deficient mouse model of autism. Neuropsychopharmacology 43:1779-1788. [PDF file]

*       Wang W, Rein B, Tan T, Zhang F, Qin L, Yan Z (2018) Chemogenetic activation of prefrontal cortex rescues synaptic and behavioral deficits in a mouse model of 16p11.2 deletion syndrome. J. Neurosci. 38:5939-5948. [PDF file]

*       Seo JS, Zhong P, Liu A, Yan Z, Greengard P (2018) Elevation of p11 in lateral habenula mediates depression-like behavior. Molecular Psychiatry 23:1113-1119. [PDF file]

*       Tang Y, Min Z, Xiang XJ, Liu L, Ma YL, Zhu BL, Song L, Tang J, Deng XJ, Yan Z, Chen GJ (2018) Estrogen-related receptor alpha is involved in Alzheimer's disease-like pathology. Exp Neurol. 305:89-96. [PDF file]

*       Wei J, Zhong P, Qin L, Tan T, Yan Z (2018) Chemicogenetic restoration of the prefrontal cortex to amygadala pathway ameliorates stress-induced deficits. Cerebral Cortex 28:1980-1990. [PDF file] *Recommended by Faculty of 1000



*       Zhong P, Hu Z, Jiang H, Yan Z, Feng J (2017) Dopamine induces oscillatory activity in human midbrain neurons with Parkin mutations. Cell Reports 19:1033-1044. [PDF file]

*       Seo JS, Wei J, Qin L, Kim Y, Yan Z, Greengard P (2017) Molecular and cellular basis for stress-induced depression. Molecular Psychiatry 22:1440-1447. [PDF file]

*       Cheng J, Liu A, Shi MY, Yan Z (2017) Disrupted glutamatergic transmission in prefrontal cortex contributes to behavioral abnormality in an animal model of ADHD. Neuropsychopharmacology 42:2096-2104. [PDF file]

*       Yang J, Liu AY, Tang B, Luo D, Lai YJ, Zhu BL, Wang XF, Yan Z, Chen GJ (2017) Chronic nicotine differentially affects murine transcriptome profiling in isolated cortical interneurons and pyramidal neurons. BMC Genomics 18:194. [PDF file]



*       Yan Z, Kim E, Datta D, Lewis D, Soderling S (2016) Synaptic actin dysregulation, a convergent mechanism of mental disorders? J. Neuroscience 36:11411-7. [PDF file] (review)

*       Qin L, Liu W, Ma K, Wei J, Zhong P, Cho K, Yan Z (2016) The ADHD-linked human dopamine D4 receptor variant D4.7 induces over-suppression of NMDA receptor function in prefrontal cortex. Neurobiology of Disease 95:194-203. [PDF file]

*       Deng Y, Wei J, Cheng J, Zhong P, Xiong Z, Liu A, Lin L, Chen SD, Yan Z (2016) Partial amelioration of synaptic and cognitive deficits by inhibiting cofilin dephosphorylation in an animal model of Alzheimer's disease. J. Alzheimer's Disease 53:1419-32. [PDF file]

*       Wei J, Xiong Z, Lee JB, Cheng J, Duffney LJ, Matas E, Yan Z (2016) Histone modification of Nedd4 ubiquitin ligase controls the loss of AMPA receptors and cognitive impairment induced by repeated stress. J. Neurosci. 36:2119-30. [PDF file]

*       Zhong P, Liu W, Yan Z (2016) Aberrant regulation of synchronous network activity by the ADHD-associated human dopamine D4 receptor variant D4.7 in prefrontal cortex. J. Physiol. 594:135-47. [PDF file]

*       Xu Z, Jiang H, Zhong P, Yan Z, Chen SD, Feng J (2016) Direct conversion of human fibroblasts to induced serotonergic neurons. Molecular Psychiatry 21:62-70. [PDF file]

*       Zhong P and Yan Z (2016) Distinct physiological effects of dopamine D4 receptors on prefrontal cortical pyramidal neurons and fast-spiking interneurons. Cerebral Cortex 21:62-70. [PDF file]

*       Yuen EY, Wei J, Yan Z (2016) Estrogen in prefrontal cortex blocks stress-induced cognitive impairments in female rats. J. Steroid Biochem. & Mol. Biol. 160:221-6. [PDF file] (review)



*       Duffney LJ, Zhong P, Wei J, Matas E, Cheng J, Qin L, Ma K, Dietz DM, Kajiwara Y, Buxbaum JD, Yan Z (2015) Autism-like deficits in Shank3-deficient mice are rescued by targeting actin regulators. Cell Reports 11:1400-1413. [PDF file] *Reported in Simons Foundation SFARI, Science Daily, etc.

*       Jiang H, Xu Z, Zhong P, Ren Y, Liang G, Schilling HA, Hu Z, Zhang Y, Wang X, Chen S, Yan Z, Feng J (2015) Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons. Nature Communications 6:10100. [PDF file]

*       Wei J, Graziane NM, Gu Z, and Yan Z (2015) DISC1 protein regulates GABAA receptor trafficking and inhibitory synaptic transmission in cortical neurons. J. Biol. Chem. 290: 27680-7. [PDF file]

*       Tang B, Luo D, Yang J, Xu XY, Zhu BL, Wang X, Yan Z, Chen GJ (2015) Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex. Scientific Reports 5:14099. [PDF file]

*       Hu Z, Pu J, Jiang H, Zhong P, Qiu J, Li F, Wang X, Zhang B, Yan Z, Feng J (2015) Generation of naivetropic induced pluripotent stem cells from Parkinson's disease patients for high efficiency genetic manipulation and disease modeling. Stem Cells Dev. 24:2591-604. [PDF file]

*       Plattner F, Hayashi K, Hernandez A, Benavides DR, Tassin TC, Tan C, Day J, Fina MW, Yuen EY, Yan Z, Goldberg MS, Nairn AC, Greengard P, Nestler EJ, Taussig R, Nishi A, Houslay MD & Bibb JA (2015) The role of ventral striatal cAMP signaling in stress-induced behaviors. Nature Neuroscience 18:1094-100. [PDF file]



*       Cheng J, Xiong Z, Duffney LJ, Wei J, Liu AY, Liu S, Chen GJ, Yan Z (2014) Methylphenidate exerts dose-dependent effects on glutamate receptors and behaviors. Biol. Psychiatry 76:953-62. [PDF file]

*       Yuen EY, Qin L, Wei J, Liu W, Liu A and Yan Z (2014) Synergistic regulation of glutamatergic transmission by serotonin and norepinephrine reuptake inhibitors in prefrontal cortical neurons. J. Biol. Chem. 289:25177-85. [PDF file]

*       Gu Z, Cheng J, Zhong P, Qin L, Liu W, Yan Z (2014) Aβ selectively impairs mGluR7 modulation of NMDA signaling in basal forebrain cholinergic neurons: implication in Alzheimer's disease. J. Neurosci. 34:13614-13628. [PDF file]

*       Smith KR, Davenport EC, Wei J, Li X, Pathania M, Vaccaro V, Yan Z, Kittler JT (2014) GIT1 and βPIX link Rac1 signalling to GABAA receptor cluster stability and inhibitory synapse strength. Cell Reports 9:298-310. [PDF file]

*       Plattner F, Hernandez A, Kistler TM, Pozo K, Zhong P, Yuen EY, Tan C, Hawasli AH, Cooke SF, Nishi A, Guo A, Weiderhold T, Yan Z, Bibb JA (2014) Memory enhancement by targeting Cdk5 regulation of NR2B. Neuron 81:1070-83. [PDF file]

*       Hayashi-Takagi A, Araki Y, Nakamura M, Vollrath B, Duron SG, Yan Z, Kasai H, Huganir RL, Campbell DA, Sawa A (2014) PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. Proc. Natl. Acad. Sci. USA 111:6461-6. [PDF file]

*       Wei J, Graziane NM, Wang H, Zhong P, Wang Q, Liu W, Hayashi-Takagi A, Korth C, Sawa A, Brandon NJ, Yan Z (2014) Regulation of NMDA receptors by Disrupted-in-Schizophrenia-1 (DISC1). Biol. Psychiatry 75:414-24. [PDF file] *Featured in Biological Psychiatry

*       Wang Q, Xiao B, Cui S, Song H, Qian Y, Dong L, An H, Cui Y, Zhang W, He Y, Zhang J, Yang J, Zhang F, Hu G, Gong X, Yan Z, Zheng Y, Wang X (2014) Triptolide with multiple modes of action improves learning performance in the 5XFAD Alzheimer's disease mouse model. Disease Models & Mechanisms 7:1385-95. [PDF file]

*       Deng Y, Xiong Z, Chen P, Wei J, Chen SD, Yan Z (2014) β-Amyloid Impairs the regulation of NMDA receptors by Glycogen Synthase Kinase 3. Neurobiol. Aging 35:449-59. [PDF file]

*       Wei J, Yuen EY, Liu W, Li X, Zhong P, Karatsoreos IN, McEwen BS, Yan Z (2014) Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Molecular Psychiatry 19:588-98. [PDF file] *Recommended by Faculty of 1000; reported in Los Angeles Times, England's Daily Mail, Huffington Post, etc.



*       Duffney LJ, Wei J, Cheng J, Liu W, Smith KR, Kittler JT, Yan Z (2013) Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism. J. Neurosci. 33:15767-78. [PDF file]

*       Vithlani M, Hines RM, Zhong P, Terunuma M, Hines DJ, Revilla-Sanchez R, Jurd R, Haydon P, Rios M, Brandon N, Yan Z, Moss SJ (2013) Effects of BNDF on neurogenesis and depression depend upon phosphorylation of the GABAAR γ2 subunit. J. Neurosci. 33:15567-77. [PDF file]

*       Cheng J, Liu W, Duffney LJ, Yan Z (2013) SNARE proteins are essential in the potentiation of NMDAR currents by group II metabotropic glutamate receptors. J. Physiol. 591:3935-47. [PDF file]

*       Yuen EY, Zhong P, Li X, Wei J, Yan Z (2013) Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals. J. Biol. Chem. 288:26112-20. [PDF file]

*       Chen GJ, Xiong Z, Yan Z (2013) Ab impairs nicotinic regulation of inhibitory synaptic transmission and interneuron excitability in prefrontal cortex. Molecular Neurodegeneration 8:3. [PDF file]



*       Yuen EY, Wei J, Liu W, Zhong P, Li X, Yan Z (2012) Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 73:962-77. [PDF file] *Featured by the Cell Press; reported in TopNews, ABC Science, MedicalNewsToday, etc.

*       Lee JB, Wei J, Liu W, Cheng J, Feng J, Yan Z (2012) Histone Deacetylase 6 gates the synaptic action of acute stress in prefrontal cortex. J. Physiology 90:1535-46. [PDF file]

*       Yuen EY, Wei J, Zhong P, Yan Z (2012) Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of Huntington's disease. Neurobiology of Disease 46:497-502. [PDF file]

*       Jiang H, Ren Y, Yuen EY, Zhong P, Ghaedi M, Hu Z, Azabdaftari G, Nakaso K, Yan Z, Feng J (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons. Nature Communications 3:668. [PDF file]

*       Gu Z, Liu W, Wei J, Yan Z (2012) Regulation of NMDA receptors by metabotropic glutamate receptor 7. J. Biol. Chem. 287:10265-75. [PDF file] * Selected as "Papers of the Week"

*       Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z (2012) The novel antipsychotic drug lurasidone enhances NMDA receptor-mediated synaptic responses. Mol. Pharm. 81:113-9. [PDF file]



*       Popoli M, Yan Z, McEwen BS, Sanacora G (2011) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nature Review Neuroscience 13:22-37. [PDF file]

*       Yuen EY, Liu W, Karatsoreos IN, Ren Y, Feng J, McEwen BS, Yan Z (2011) Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Mol. Psychiatry 16:156-70. [PDF file] [supporting information] (cover article)

*       Mandal M, Wei J, Zhong P, Chen J, Duffney LJ, Liu W, Yuen EY, Twelvetrees AE, Li S, Li XJ, Kittler JT, Yan Z (2011) Impaired AMPA receptor trafficking and function by mutant huntingtin. J. Biol. Chem. 286:33719-28. [PDF file]

*       Zhong P, Yan Z (2011) Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine. PLoS One 6(2):e16970. [PDF file]

*       Yuen EY, Yan Z (2011) Cellular mechanisms for the dopamine D4 receptor-induced homeostatic regulation of AMPA receptors. J. Biol. Chem. 286:24957-65. [PDF file]

*       Wang Q, Charych EI, Pulito VL, Lee J, Graziane NM, Crozier RA, Revilla-Sanchez R, Kelly M, Dunlop AJ, Murdoch H, Taylor N, Xie Y, Pausch M, Hayashi-Takagi A, Bates B, Kariya K, Sawa A, Weinberg RJ, Moss SJ, Houslay MD, Yan Z, Brandon NJ (2011) The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Mol. Psychiatry 16:1006-23. [PDF file]

*       Wang D, Yuen EY, Zhou Y, Yan Z, Xiang YK (2011) Amyloid {beta} peptide1-42 induces internalization and degradation of β2 adrenergic receptor in prefrontal cortical neurons. J Biol Chem. 286:31852-63. [PDF file]

*       Liu W, Dou F, Feng J, Yan Z (2011) RACK1 is involved in β-amyloid impairment of muscarinic regulation of GABAergic transmission. Neurobiol. Aging 32:1818-26. [PDF file]



*       Yuen EY, Zhong P, Yan Z (2010) Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proc. Natl. Acad. Sci. USA107:22308-13. [PDF file] [supporting information] 

*       Liu W, Yuen EY, Yan Z (2010) The stress hormone corticosterone increases synaptic AMPA receptors via SGK regulation of the GDI-Rab4 complex. J. Biol. Chem. 285:6101-8. [PDF file]

*       Wei J, Liu W, Yan Z (2010) Regulation of AMPA receptor trafficking and function by glycogen synthase kinase 3. J. Biol. Chem. 285:26369-76. [PDF file]

*       Yuen EY, Liu W, Kafri T, van Praag H, Yan Z (2010) Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons. J. Physiol. 588:2361-71. [PDF file]  (cover article)

*       Twelvetrees AE, Yuen EY, Arancibia-Carcamo IL, Rostaing P, Lumb MJ, Humbert S, Triller A, Saudou F, Yan Z, Kittler JT (2010) Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant huntingtin. Neuron 65:53-65. [PDF file]

*       Hayashi-Takagi A, Takaki M, Graziane NM, Seshadri S, Murdoch H, Dunlop AJ, Makino Y, Seshadri AJ, Ishizuka K, Srivastava DP, Xie Z, Baraban JM, Houslay MD, Tomoda T, Brandon NJ, Kamiya A, Yan Z, Penzes P, Sawa A (2010) Disrupted-in-Schizophrenia-1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci. 13:327-32. [PDF file]

*       Joiner MA, Lise MF, Yuen EY, Kam A, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD, Burette AC, Weinberg RJ, Law PY, El-Husseini A, Yan Z, Hell JW (2010) Assembly of a β2-adrenergic receptor- GluR1 signaling complex for localized cAMP signaling. EMBO J 29:482-95. [PDF file]



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Last updated: 6/2019