Loading...
Sign in to edit your profile (add interests, mentoring, photo, etc.)

    Xianjin Zhou

    Address9500 Gilman Drive #0667
    CA La Jolla 92093
    Phone858-822-3709
    vCardDownload vCard

      Collapse Overview 
      Collapse Overview

      Biography

      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.


      Collapse Research 
      Collapse Research Activities and Funding
      Mice Harboring Human DISC1-Boymaw Fusion Transcripts
      NIH/NIMH R21MH086075Jun 2, 2009 - May 31, 2011
      Role: Principal Investigator
      Understanding the Role of COMT Variants in Sensorimotor Gating
      NIH/NIMH R33MH083499May 15, 2008 - Apr 30, 2012
      Role: Principal Investigator
      Understanding the Role of COMT Variants in Sensorimotor Gating
      NIH/NIMH R21MH083499May 15, 2008 - Apr 30, 2010
      Role: Principal Investigator
      Striatal Dopamine D1 Functions on Modulating Prepulse Inhibition
      NIH/NIMH R21MH081037Apr 1, 2008 - Jun 30, 2010
      Role: Principal Investigator
      Sp4 Pathway in the Modulation of Sensorimotor Gating and Memory
      NIH/NIMH R01MH073991Dec 1, 2004 - Jul 31, 2015
      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.
      List All   |   Timeline
      1. Higa KK, Young JW, Ji B, Nichols DE, Geyer MA, Zhou X. Striatal dopamine D1 receptor suppression impairs reward-associative learning. Behav Brain Res. 2017 Jan 29; 323:100-110. PMID: 28143767.
        View in: PubMed
      2. Ji B, Higa KK, Kelsoe JR, Zhou X. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders. EBioMedicine. 2015 Aug; 2(8):907-16. PMID: 26425698.
        View in: PubMed
      3. Higa KK, Ji B, Buell MR, Risbrough VB, Powell SB, Young JW, Geyer MA, Zhou X. Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice. Int J Neuropsychopharmacol. 2015; 18(11). PMID: 26037489.
        View in: PubMed
      4. Ji B, Kim M, Higa KK, Zhou X. 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; 168(4):284-95. PMID: 25943690.
        View in: PubMed
      5. Young JW, Kamenski ME, Higa KK, Light GA, Geyer MA, Zhou X. GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders. Neuropsychopharmacology. 2015 Apr 24. PMID: 25907107.
        View in: PubMed
      6. Ji B, Higa KK, Kim M, Zhou L, Young JW, Geyer MA, Zhou X. Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish family with major psychiatric disorders. Hum Mol Genet. 2014 Jun 6. PMID: 24908665.
        View in: PubMed
      7. Risbrough V, Ji B, Hauger R, Zhou X. Generation and Characterization of Humanized Mice Carrying COMT158 Met/Val Alleles. Neuropsychopharmacology. 2014 Jul; 39(8):1823-32. PMID: 24509724.
        View in: PubMed
      8. Ji B, Wang X, Pinto-Duarte A, Kim M, Caldwell S, Young JW, Behrens MM, Sejnowski TJ, Geyer MA, Zhou X. Prolonged Ketamine Effects in Sp4 Hypomorphic Mice: Mimicking Phenotypes of Schizophrenia. PLoS One. 2013; 8(6):e66327. PMID: 23823008.
        View in: PubMed
      9. Kim M, Soontornniyomkij V, Ji B, Zhou X. System-wide immunohistochemical analysis of protein co-localization. PLoS One. 2012; 7(2):e32043. PMID: 22363794.
        View in: PubMed
      10. Young JW, Powell SB, Scott CN, Zhou X, Geyer MA. 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. PMID: 21458500.
        View in: PubMed
      11. Zhou X, Nie Z, Roberts A, Zhang D, Sebat J, Malhotra D, Kelsoe JR, Geyer MA. Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders. Hum Mol Genet. 2010 Oct 1; 19(19):3797-805. PMID: 20634195.
        View in: PubMed
      12. Young JW, Zhou X, Geyer MA. Animal models of schizophrenia. Curr Top Behav Neurosci. 2010; 4:391-433. PMID: 21312408.
        View in: PubMed
      13. Powell SB, Zhou X, Geyer MA. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009 Dec 7; 204(2):282-94. PMID: 19397931.
        View in: PubMed
      14. Zhou X, Tang W, Greenwood TA, Guo S, He L, Geyer MA, Kelsoe JR. Transcription factor SP4 is a susceptibility gene for bipolar disorder. PLoS One. 2009; 4(4):e5196. PMID: 19401786.
        View in: PubMed
      15. Zhou X, Barrett TB, Kelsoe JR. Promoter variant in the GRK3 gene associated with bipolar disorder alters gene expression. Biol Psychiatry. 2008 Jul 15; 64(2):104-10. PMID: 18359007.
        View in: PubMed
      16. Zhou X, Qyang Y, Kelsoe JR, Masliah E, Geyer MA. Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice. Genes Brain Behav. 2007 Apr; 6(3):269-76. PMID: 16899055.
        View in: PubMed