Xianjin Zhou

Title(s)Associate Adjunct Professor, Psychiatry
SchoolVc-health Sciences-schools
Address9500 Gilman Drive #
La Jolla CA 92093
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    Dr. Zhou received his PhD degree from Institute of Molecular Biology, Chinese Academy of Agricultural Sciences, Beijing. He completed his postdoctoral training in mouse molecular genetics at Robert Wood Johnson Medical School-UMDNJ and UCSD. Dr. Zhou was appointed as an Assistant professor in 2009, and has been the principal investigator on research grants from NIMH and NARSAD.

    Research Interests

    As a molecular biologist, I am interested in understanding molecular mechanisms underlying human psychiatric disorders. With the funding support of NMIH R01 and R21 grants, we have generated several humanized mouse lines expressing different susceptibility genes including Sp4, DISC1-Boymaw fusion gene, and COMT Met/Val. The molecular mechanisms and pathways of the susceptibility genes have been studied at molecular, cellular, and system levels.

    Sp4 Gene

    Sp4 gene encodes a neuron-specific transcription factor that binds GC-rich DNA in the promoter of most genes. Its expression begins from E9.5 during mouse embryogenesis and persists throughout the adulthood. Sp4 knockout mice displayed reduced hippocampal size, subtle hippocampal vacuolization, as well as impaired postnatal development of hippocampal dentate gyrus. Sp4 hypomorphic mice displayed schizophrenia endophenotypes including PPI deficit, learning and memory deficit, and exaggerated responses to NMDAR antagonists. Human SP4 gene was deleted in patients with schizophrenia. We are conducting genetic rescue experiments to restore Sp4 gene expression in excitatory and GABAergic inhibitory neurons with EMX1-Cre and Dlx6a-Cre respectively to dissect out neural circuits modulating the behavioral deficits.

    DISC1-Boymaw Fusion Gene

    A balanced chromosome translocation was identified in a large Scottish schizophrenia and major depression family. The t(1; 11) translocation appears to be the causal genetic lesion with 70% penetrance for schizophrenia and major depression. Therefore, investigation of molecular mechanisms underlying schizophrenia and major depression in the Scottish family will be invaluable for our understanding of the molecular basis of these major psychiatric disorders. Molecular studies identified the disruption of the DISC1 gene by the chromosome translocation at chromosome 1q42. However, no gene was found to be disrupted by the other breakpoint at chromosome 11q14.3. Therefore, the disruption of the single DISC1 gene has been assumed to contribute to the pathogenesis of schizophrenia and major depression. However, our analysis found that a novel gene, Boymaw, was also disrupted by the translocation at chromosome 11q14.3, and the DISC1-Boymaw fusion genes were generated. We found that that the DISC1-Boymaw fusion protein, predominantly localized in mitochondria, inhibits both intracellular NADH oxidoreductase activities and protein translation. We generated humanized DISC1-Boymaw mice with gene targeting to examine the in vivo functions of the fusion genes. Consistent with the in vitro studies on the DISC1-Boymaw fusion gene, both oxidoreductase activities and protein translation are decreased in the brains of the humanized mice. The humanized mice display behaviors related to schizophrenia and depression. Dysregulation of protein translation has been documented in several mental disorders including fragile X mental retardation and autism. Optimal level of protein translation may be essential for neural plasticity. Expression of the DISC1-Boymaw fusion gene reduces protein translation and thereby contributes to the pathogenesis of major psychiatric disorders.

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    Collapse Research Activities and Funding
    Modeling Anti-NMDAR1 Autoantibodies in Psychiatric Disorders
    NIH R21MH123705Jul 1, 2020 - Jun 30, 2022
    Role: Principal Investigator
    Neuroinflammation in Generation of NMDAR Autoantibodies
    NIH R21MH116186Nov 27, 2018 - Oct 31, 2021
    Role: Principal Investigator
    Mice Harboring Human DISC1-Boymaw Fusion Transcripts
    NIH R21MH086075Jun 2, 2009 - May 31, 2011
    Role: Principal Investigator
    Understanding the Role of COMT Variants in Sensorimotor Gating
    NIH R33MH083499May 15, 2008 - Apr 30, 2012
    Role: Principal Investigator
    Understanding the Role of COMT Variants in Sensorimotor Gating
    NIH R21MH083499May 15, 2008 - Apr 30, 2010
    Role: Principal Investigator
    Striatal Dopamine D1 Functions on Modulating Prepulse Inhibition
    NIH R21MH081037Apr 1, 2008 - Jun 30, 2010
    Role: Principal Investigator
    Sp4 Pathway in the Modulation of Sensorimotor Gating and Memory
    NIH R01MH073991Dec 1, 2004 - Jul 31, 2016
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Preventive and Therapeutic Autoantibodies Protect against Neuronal Excitotoxicity. J Psychiatr Brain Sci. 2023; 8(3). Zhou X. PMID: 37502631; PMCID: PMC10373126.
      View in: PubMed   Mentions:
    2. Over-representation of potential SP4 target genes within schizophrenia-risk genes. Mol Psychiatry. 2022 02; 27(2):849-854. Zhou X. PMID: 34750502; PMCID: PMC9054665.
      View in: PubMed   Mentions: 4     Fields:    Translation:Animals
    3. Chronic presence of blood circulating anti-NMDAR1 autoantibodies impairs cognitive function in mice. PLoS One. 2021; 16(9):e0256972. Yue W, Caldwell S, Risbrough V, Powell S, Zhou X. PMID: 34473764; PMCID: PMC8412244.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCellsPHPublic Health
    4. Cognitive Impact by Blood Circulating Anti-NMDAR1 Autoantibodies. J Psychiatr Brain Sci. 2021; 6. Zhou X. PMID: 34307898; PMCID: PMC8301263.
      View in: PubMed   Mentions: 1  
    5. A novel one-step quick assay for detection of SARS-COV2 antibodies across mammalian species. PeerJ. 2021; 9:e11381. Zhou X. PMID: 33987037; PMCID: PMC8086566.
      View in: PubMed   Mentions: 2     Fields:    
    6. Chronic nicotine, but not suramin or resveratrol, partially remediates the mania-like profile of dopamine transporter knockdown mice. Eur Neuropsychopharmacol. 2021 01; 42:75-86. Kwiatkowski MA, Roberts BZ, van Enkhuizen J, Ji B, Zhou X, Young JW. PMID: 33191077; PMCID: PMC8853461.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimals
    7. Heritable Differences in Catecholamine Signaling Modulate Susceptibility to Trauma and Response to Methylphenidate Treatment: Relevance for PTSD. Front Behav Neurosci. 2019; 13:111. Deslauriers J, Toth M, Zhou X, Risbrough VB. PMID: 31164811; PMCID: PMC6534065.
      View in: PubMed   Mentions: 5  
    8. A novel animal model for neuroinflammation and white matter degeneration. PeerJ. 2017; 5:e3905. Ji B, Higa K, Soontornniyomkij V, Miyanohara A, Zhou X. PMID: 29104820; PMCID: PMC5669272.
      View in: PubMed   Mentions: 3     Fields:    
    9. Striatal dopamine D1 receptor suppression impairs reward-associative learning. Behav Brain Res. 2017 04 14; 323:100-110. Higa KK, Young JW, Ji B, Nichols DE, Geyer MA, Zhou X. PMID: 28143767.
      View in: PubMed   Mentions: 12     Fields:    Translation:Animals
    10. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders. EBioMedicine. 2015 Aug; 2(8):909-18. Ji B, Higa KK, Kelsoe JR, Zhou X. PMID: 26425698; PMCID: PMC4563114.
      View in: PubMed   Mentions: 23     Fields:    Translation:HumansCells
    11. Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice. Int J Neuropsychopharmacol. 2015 Jun 02; 18(11):pyv063. Higa KK, Ji B, Buell MR, Risbrough VB, Powell SB, Young JW, Geyer MA, Zhou X. PMID: 26037489; PMCID: PMC4756721.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    12. Boymaw, overexpressed in brains with major psychiatric disorders, may encode a small protein to inhibit mitochondrial function and protein translation. Am J Med Genet B Neuropsychiatr Genet. 2015 Jun; 168B(4):284-95. Ji B, Kim M, Higa KK, Zhou X. PMID: 25943690.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansAnimalsCells
    13. GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders. Neuropsychopharmacology. 2015 Nov; 40(12):2715-26. Young JW, Kamenski ME, Higa KK, Light GA, Geyer MA, Zhou X. PMID: 25907107; PMCID: PMC4864647.
      View in: PubMed   Mentions: 21     Fields:    Translation:Animals
    14. Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish family with major psychiatric disorders. Hum Mol Genet. 2014 Nov 01; 23(21):5683-705. Ji B, Higa KK, Kim M, Zhou L, Young JW, Geyer MA, Zhou X. PMID: 24908665; PMCID: PMC4189903.
      View in: PubMed   Mentions: 23     Fields:    Translation:HumansAnimalsCells
    15. Generation and characterization of humanized mice carrying COMT158 Met/Val alleles. Neuropsychopharmacology. 2014 Jul; 39(8):1823-32. Risbrough V, Ji B, Hauger R, Zhou X. PMID: 24509724; PMCID: PMC4059890.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimals
    16. Prolonged Ketamine Effects in Sp4 Hypomorphic Mice: Mimicking Phenotypes of Schizophrenia. PLoS One. 2013; 8(6):e66327. Ji B, Wang X, Pinto-Duarte A, Kim M, Caldwell S, Young JW, Behrens MM, Sejnowski TJ, Geyer MA, Zhou X. PMID: 23823008; PMCID: PMC3688895.
      View in: PubMed   Mentions: 15     Fields:    Translation:AnimalsCells
    17. System-wide immunohistochemical analysis of protein co-localization. PLoS One. 2012; 7(2):e32043. Kim M, Soontornniyomkij V, Ji B, Zhou X. PMID: 22363794; PMCID: PMC3283725.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    18. The effect of reduced dopamine D4 receptor expression in the 5-choice continuous performance task: Separating response inhibition from premature responding. Behav Brain Res. 2011 Sep 12; 222(1):183-92. Young JW, Powell SB, Scott CN, Zhou X, Geyer MA. PMID: 21458500; PMCID: PMC3531561.
      View in: PubMed   Mentions: 41     Fields:    Translation:Animals
    19. Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders. Hum Mol Genet. 2010 Oct 01; 19(19):3797-805. Zhou X, Nie Z, Roberts A, Zhang D, Sebat J, Malhotra D, Kelsoe JR, Geyer MA. PMID: 20634195; PMCID: PMC2935857.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimals
    20. Animal models of schizophrenia. Curr Top Behav Neurosci. 2010; 4:391-433. Young JW, Zhou X, Geyer MA. PMID: 21312408.
      View in: PubMed   Mentions: 35     Fields:    Translation:HumansAnimals
    21. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009 Dec 07; 204(2):282-94. Powell SB, Zhou X, Geyer MA. PMID: 19397931; PMCID: PMC2735602.
      View in: PubMed   Mentions: 97     Fields:    Translation:Animals
    22. Transcription factor SP4 is a susceptibility gene for bipolar disorder. PLoS One. 2009; 4(4):e5196. Zhou X, Tang W, Greenwood TA, Guo S, He L, Geyer MA, Kelsoe JR. PMID: 19401786; PMCID: PMC2674320.
      View in: PubMed   Mentions: 30     Fields:    Translation:HumansAnimals
    23. Promoter variant in the GRK3 gene associated with bipolar disorder alters gene expression. Biol Psychiatry. 2008 Jul 15; 64(2):104-10. Zhou X, Barrett TB, Kelsoe JR. PMID: 18359007; PMCID: PMC6528791.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    24. Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice. Genes Brain Behav. 2007 Apr; 6(3):269-76. Zhou X, Qyang Y, Kelsoe JR, Masliah E, Geyer MA. PMID: 16899055.
      View in: PubMed   Mentions: 36     Fields:    Translation:AnimalsCells
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