Z Xu

Summary

Affiliation: University of Massachusetts Medical School
Country: USA

Publications

  1. pmc Widespread aggregation of mutant VAPB associated with ALS does not cause motor neuron degeneration or modulate mutant SOD1 aggregation and toxicity in mice
    Linghua Qiu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01602, USA
    Mol Neurodegener 8:1. 2013
  2. pmc Does a loss of TDP-43 function cause neurodegeneration?
    Zuo Shang Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, 817 LRB, Worcester, MA 01605, USA
    Mol Neurodegener 7:27. 2012
  3. pmc ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes
    Cynthia M J Higgins
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01655, USA
    BMC Neurosci 4:16. 2003
  4. pmc A construct with fluorescent indicators for conditional expression of miRNA
    Linghua Qiu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
    BMC Biotechnol 8:77. 2008
  5. pmc An RNA polymerase II construct synthesizes short-hairpin RNA with a quantitative indicator and mediates highly efficient RNAi
    Hongxia Zhou
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School 364 Plantation Street, Worcester, MA 01605, USA
    Nucleic Acids Res 33:e62. 2005
  6. ncbi request reprint Mitochondrial degeneration in amyotrophic lateral sclerosis
    Zuoshang Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, Massachusetts 01605, USA
    J Bioenerg Biomembr 36:395-9. 2004
  7. ncbi request reprint Mechanism and treatment of motoneuron degeneration in ALS: what have SOD1 mutants told us?
    Z Xu
    Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655, USA
    Amyotroph Lateral Scler Other Motor Neuron Disord 1:225-34. 2000
  8. ncbi request reprint Temporal and spatial variations in slow axonal transport velocity along peripheral motoneuron axons
    Z Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Neuroscience 102:193-200. 2001
  9. ncbi request reprint Overexpression of neurofilament subunit M accelerates axonal transport of neurofilaments
    Z Xu
    Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Brain Res 866:326-32. 2000
  10. ncbi request reprint Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis
    J Kong
    Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA
    Neurosci Lett 281:72-4. 2000

Research Grants

Collaborators

Detail Information

Publications36

  1. pmc Widespread aggregation of mutant VAPB associated with ALS does not cause motor neuron degeneration or modulate mutant SOD1 aggregation and toxicity in mice
    Linghua Qiu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01602, USA
    Mol Neurodegener 8:1. 2013
    ..Furthermore, the amount of VAPB protein is reported to be reduced in sporadic ALS patients and mutant SOD1G93A mice, leading to the hypothesis that wild type VAPB plays a role in the pathogenesis of ALS without VAPB mutations...
  2. pmc Does a loss of TDP-43 function cause neurodegeneration?
    Zuo Shang Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, 817 LRB, Worcester, MA 01605, USA
    Mol Neurodegener 7:27. 2012
    ....
  3. pmc ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes
    Cynthia M J Higgins
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01655, USA
    BMC Neurosci 4:16. 2003
    ..To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1G93A...
  4. pmc A construct with fluorescent indicators for conditional expression of miRNA
    Linghua Qiu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
    BMC Biotechnol 8:77. 2008
    ..Furthermore, because microRNA (miRNA) targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals...
  5. pmc An RNA polymerase II construct synthesizes short-hairpin RNA with a quantitative indicator and mediates highly efficient RNAi
    Hongxia Zhou
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School 364 Plantation Street, Worcester, MA 01605, USA
    Nucleic Acids Res 33:e62. 2005
    ..This system may be adapted for in vivo shRNA expression and gene silencing...
  6. ncbi request reprint Mitochondrial degeneration in amyotrophic lateral sclerosis
    Zuoshang Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, Massachusetts 01605, USA
    J Bioenerg Biomembr 36:395-9. 2004
    ..Thus, this appears to be a new form of mitochondrial vacuolation and we term this as mitochondrial vacuolation by intermembrane space expansion or MVISE...
  7. ncbi request reprint Mechanism and treatment of motoneuron degeneration in ALS: what have SOD1 mutants told us?
    Z Xu
    Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655, USA
    Amyotroph Lateral Scler Other Motor Neuron Disord 1:225-34. 2000
    ....
  8. ncbi request reprint Temporal and spatial variations in slow axonal transport velocity along peripheral motoneuron axons
    Z Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Neuroscience 102:193-200. 2001
    ..These differences provide a basis for the regional deficiencies in axonal transport associated with several neurological disorders...
  9. ncbi request reprint Overexpression of neurofilament subunit M accelerates axonal transport of neurofilaments
    Z Xu
    Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Brain Res 866:326-32. 2000
    ....
  10. ncbi request reprint Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis
    J Kong
    Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA
    Neurosci Lett 281:72-4. 2000
    ..These results illustrate a beneficial role of neurofilaments in ALS and call into question of several hypotheses regarding the role of neurofilaments in the development of ALS...
  11. ncbi request reprint Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis
    Hongliu Ding
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605 2324, USA
    Aging Cell 2:209-17. 2003
    ..Thus, RNAi is a promising therapy for ALS and other disorders caused by dominant, gain-of-function gene mutations...
  12. pmc Nerve injection of viral vectors efficiently transfers transgenes into motor neurons and delivers RNAi therapy against ALS
    Rui Wu
    Department of Biochemistry, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Antioxid Redox Signal 11:1523-34. 2009
    ..These results highlight the potential and the challenges in delivering RNAi therapy by gene therapy...
  13. ncbi request reprint Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS
    Cynthia M J Higgins
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Neurosci 22:RC215. 2002
    ..By immunoelectron microscopy, we show that SOD1 is present within mitochondria at similar concentrations as in the cytoplasm. Thus SOD1, in addition to being a cytosolic enzyme, is present inside mitochondria in the CNS...
  14. ncbi request reprint RNAi therapy: dominant disease gene gets silenced
    Z Xu
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St 817 LRB, Worcester, MA 01655, USA
    Gene Ther 12:1159-60. 2005
  15. ncbi request reprint Peripheral axotomy slows motoneuron degeneration in a transgenic mouse line expressing mutant SOD1 G93A
    J Kong
    Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Comp Neurol 412:373-80. 1999
    ..Interestingly, all of the increased surviving axons were in the axon group with diameters smaller than 4.5 microm. This result suggests an apparent threshold of vulnerability that is correlated with axon size...
  16. ncbi request reprint An RNAi strategy for treatment of amyotrophic lateral sclerosis caused by mutant Cu,Zn superoxide dismutase
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, Massachusetts 01605, USA
    J Neurochem 92:362-7. 2005
    ..Using this strategy, all mutants and wild-type genes are inhibited by RNAi. The wild-type SOD1 function is then replaced by designed wild-type SOD1 genes that are resistant to the RNAi. Here we demonstrate the concept of this strategy...
  17. pmc Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression
    Hongyan Wang
    Department of Biochemistry and Molecular Pharmacology, Chemical Biology Program, Cell Biology, and Neuroscience Program, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 283:15845-52. 2008
    ..These results bring RNA interference therapy one step closer to its clinical application for treatment of chronic, devastating, and fatal CNS disorders...
  18. pmc An enhanced U6 promoter for synthesis of short hairpin RNA
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Nucleic Acids Res 31:e100. 2003
    ..Thus, this enhanced U6 promoter is useful where limited choices of shRNA sequences preclude the selection of a highly efficient RNAi target region...
  19. ncbi request reprint Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis
    Cheolwha Jung
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Neurochem 83:535-45. 2002
    ..These results demonstrate a functional defect in mitochondria in the ventral horn region and support the view that mitochondrial damage plays a role in mutant SOD1-induced motoneuron degeneration pathway...
  20. pmc Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of the gene knockout in mice
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Genet 2:e10. 2006
    ....
  21. ncbi request reprint Multiple shRNAs expressed by an inducible pol II promoter can knock down the expression of multiple target genes
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Biotechniques 41:64-8. 2006
    ..This method may be used to establish stable knockdown cell lines and may also prove useful for investigating gene-gene interactions in transgenic animals...
  22. ncbi request reprint Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo
    Xugang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, 817 LRB, Worcester, MA 01605, USA
    Neurobiol Dis 23:578-86. 2006
    ..The silencing of the mutant significantly delayed ALS onset and extended survival. Thus, RNAi can achieve allele-specific silencing and therapeutic benefit in vivo...
  23. ncbi request reprint Transgenic RNAi: Accelerating and expanding reverse genetics in mammals
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Transgenic Res 15:271-5. 2006
    ..The advent of RNAi is poised to accelerate the pace at which reverse genetics can be applied to study gene function in mammals...
  24. ncbi request reprint Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosis
    Hemachand Tummala
    Department of Biochemistry and Molecular Pharmacology, Neurology, and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:17725-31. 2005
    ..Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins...
  25. ncbi request reprint Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model
    C Jung
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA
    Neurosci Lett 304:157-60. 2001
    ..These treatments reduced levels of oxidative stress and prolonged survival. The results suggest that oxidative stress plays an active role in ALS and illustrate the potential for treatment strategies aimed specifically against ROS...
  26. ncbi request reprint Asymmetry in the assembly of the RNAi enzyme complex
    Dianne S Schwarz
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, 364 Plantation Street, Worcester, MA 01605, USA
    Cell 115:199-208. 2003
    ..Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis...
  27. ncbi request reprint A quantitative histochemical assay for activities of mitochondrial electron transport chain complexes in mouse spinal cord sections
    Cheolwha Jung
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Neurosci Methods 114:165-72. 2002
    ....
  28. pmc Designing siRNA that distinguish between genes that differ by a single nucleotide
    Dianne S Schwarz
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Genet 2:e140. 2006
    ..Our data suggest that siRNAs can be designed to discriminate between the wild-type and mutant alleles of many genes that differ by just a single nucleotide...
  29. pmc S-nitrosothiol depletion in amyotrophic lateral sclerosis
    Christopher M Schonhoff
    Department of Medicine and Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 103:2404-9. 2006
    ..SNO donor compounds may provide new therapeutic options for diseases such as ALS that are associated with deficient S-nitrosylation...
  30. ncbi request reprint Normal dendritic arborization in spinal motoneurons requires neurofilament subunit L
    Zaixiang Zhang
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester 01655, USA
    J Comp Neurol 450:144-52. 2002
    ..These results demonstrate that NF-L is a critical intrinsic factor for dendritic growth in large motoneurons...
  31. ncbi request reprint Promises and challenges in developing RNAi as a research tool and therapy for neurodegenerative diseases
    Xu Gang Xia
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, 01605, USA
    Neurodegener Dis 2:220-31. 2005
    ..We discuss the present and future challenges in the full realization of the potential for RNAi...
  32. ncbi request reprint Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Biol Chem 280:29771-9. 2005
    ..These abnormally hydrophobic SOD1 species may promote aberrant interactions of the enzyme with itself or with other cellular constituents to produce toxicity in familial ALS...
  33. pmc SMN protects cells against mutant SOD1 toxicity by increasing chaperone activity
    Tie Zou
    Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, LRB 325, Worcester, MA 01605, USA
    Biochem Biophys Res Commun 364:850-5. 2007
    ..We conclude that SMN plays a protective role in motor neurons by its chaperone activity. Our results provide support for the potential development of therapy for SMA and amyotrophic lateral sclerosis (ALS)...
  34. pmc Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice
    Hongxia Zhou
    Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Int J Biol Sci 3:242-50. 2007
    ..The results demonstrate that silencing of the PINK1 gene does not induce a reliable mouse model for Parkinson's disease, but that technically the inducible U6 promoter is useful for conditional RNAi in vivo...
  35. ncbi request reprint Mitochondrial dysfunction and its role in motor neuron degeneration in ALS
    Giovanni Manfredi
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street A 501, New York, NY 10021, USA
    Mitochondrion 5:77-87. 2005
    ....
  36. pmc Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model
    Hitoshi Kikuchi
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:6025-30. 2006
    ..Our results suggest a toxic mechanism for mutant SOD1 by which this ubiquitously expressed pathogenic protein could affect motor neuron survival and contribute to the selective motor neuronal degeneration in ALS...

Research Grants26

  1. Reverse genetics using RNAi in non-mouse mammals
    Zuoshang Xu; Fiscal Year: 2007
    ....
  2. Silencing mutant SOD1 in vivo for treatment of ALS
    Zuoshang Xu; Fiscal Year: 2007
    ..If successful, these experiments will provide impetus for further human trials of this therapeutic strategy. ..
  3. Modeling Progranulin hypomorphism for FTD in mice
    Zuoshang Xu; Fiscal Year: 2007
    ..If successful, our work will establish the first animal model for this disease, which can be used for studying neurodegeneration mechanisms and testing therapeutic strategies. ..
  4. Understanding mechanism and therapy of ALS using RNAi
    Zuoshang Xu; Fiscal Year: 2007
    ..To determine the optimal time for therapy, we will use the Tamoxifeninducible Cre recombinant system to determine at what stage of the disease induction of shRNA to suppress mutant SOD1expresion is most effective. ..
  5. DISEASE PROGRESSION AND OXIDATIVE STRESS IN ALS
    Zuoshang Xu; Fiscal Year: 2002
    ..Further, we will test whether and how anti-oxidant treatment changes the course of disease progression. ..
  6. Mitochondrial dysfunction in ALS
    Zuoshang Xu; Fiscal Year: 2003
    ..A direct association of mutant SOD1 with mitochondria will suggest that mitochondria are damaged directly by the toxicity of mutant enzyme. ..
  7. Developing animal models for diseases using RNAi
    Zuoshang Xu; Fiscal Year: 2005
    ..If successful, this technology can be widely applied as an alternative to gene knockout technology for investigation of gene functions in vivo and generation of animal disease models. ..
  8. Transgenic models of ALS caused by VAPB mutation
    Zuoshang Xu; Fiscal Year: 2010
    ..We propose to establish cell culture and transgenic mouse models to investigate how the VAPB mutation causes neuronal degeneration. Once established, these models can be used for pre-clinical tests of therapeutic compounds. ..