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Zuoshang Xu MD, PhD

InstitutionUMass Chan Medical School
DepartmentBiochemistry and Molecular Biotechnology
AddressUMass Chan Medical School
364 Plantation Street LRB
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionT.H. Chan School of Medicine

    InstitutionT.H. Chan School of Medicine
    DepartmentRNA Therapeutics Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences

    Collapse Biography 
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    Shanghai Medical College, Shanghai, , ChinaMD
    Washington University in St Louis, Saint Louis, MO, United StatesPHDNeuroscience

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    Mechanism and therapy of neurodegenerative diseases

    Zoushang Xu, Ph.D.My laboratory is working to understand the mechanism of neurodegeneration in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). ALS causes motor neuron degeneration, paralysis and death. FTD causes neurodegeneration in frontal and temporal cortex, resulting in degeneration of high brain functions, including altered personality, loss of executive ability, disabled social functions and regressive language skills. ALS and FTD are related because sometimes both diseases occur in the same patients and they share some cellular pathological features. We study these diseases by generating and analyzing animal models for these diseases. We are also developing RNAi therapy for these diseases.

    We generate and use two types of animal models. One is gene overexpression models and the other is gene knockdown models. One overexpression model that we study is mice that express mutant human copper, zinc superoxide dismutase (SOD1) gene, which causes ALS. These mice develop ALS symptoms similar to humans. We hypothesize that mitochondrial damage and chaperone dysfunction contributes to motor neuron degeneration caused by mutant SOD1. Our experimental data support this hypothesis (Xu et al., 2004; Tummala et al., 2005). In addition to these mechanistic studies, we also use these mice to test new RNAi therapy strategies (Ding et al., 2003; Schwarz et al., 2006; Xia et al., 2006a).

    For gene knockdown models, we use transgenic RNAi method that we have developed. We have demonstrated that transgenic RNAi knockdown of specific genes can recapitulate gene knockout phenotypes (Xia et al., 2006b). We have used transgenic RNAi to demonstrate that allele-specific silencing works in vivo (Xia et al., 2006a). Recently we have developed more sophisticated conditional knockdown strategies so that gene knockdown can be controlled spatially and temporally. We are using this transgenic RNAi strategy to target genes that are involved in ALS, FTD and Alzhermer’s disease.

    In developing RNAi therapy strategies, we are testing two approaches. One is to express RNAi using viral vectors to silence disease genes. The other approach is being conducted in collaboration with Dr. Tariq Rana’s lab. We are testing delivering RNAi therapy using chemically modified siRNA that has enhanced stability. By these approaches, we hope that we will bring RNAi to clinical application for treatment of neurodegenerative diseases as well as other CNS disorders.

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    One postdoctoral position is available to study the mechanism and treatment of motor neuron disease. Experience in molecular biology and neuroscience is preferred. Contact Dr. Xu for additional details.

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    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. Yusuf IO, Parsi S, Ostrow LW, Brown RH, Thompson PR, Xu Z. PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS. Neurobiol Dis. 2024 Mar; 192:106414. PMID: 38253209.
      Citations:    Fields:    
    2. Kumar MS, Fowler-Magaw ME, Kulick D, Boopathy S, Gadd DH, Rotunno M, Douthwright C, Golebiowski D, Yusuf I, Xu Z, Brown RH, Sena-Esteves M, O'Neil AL, Bosco DA. Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons. Int J Mol Sci. 2022 Dec 16; 23(24). PMID: 36555655.
      Citations:    Fields:    Translation:HumansAnimalsCells
    3. Chen Y, Krishnan G, Parsi S, Pons M, Nikolaki V, Cao L, Xu Z, Gao FB. The enhanced association between mutant CHMP2B and spastin is a novel pathological link between frontotemporal dementia and hereditary spastic paraplegias. Acta Neuropathol Commun. 2022 11 22; 10(1):169. PMID: 36414997.
      Citations:    Fields:    Translation:HumansAnimals
    4. Yusuf IO, Qiao T, Parsi S, Tilvawala R, Thompson PR, Xu Z. Protein citrullination marks myelin protein aggregation and disease progression in mouse ALS models. Acta Neuropathol Commun. 2022 09 08; 10(1):135. PMID: 36076282.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    5. Lee PJ, Kennedy Z, Wang Y, Lu Y, Cefaliello C, Uyan ?, Song CQ, Godinho BMC, Xu Z, Rusckowski M, Xue W, Brown RH. Imaging Net Retrograde Axonal Transport In Vivo: A Physiological Biomarker. Ann Neurol. 2022 05; 91(5):716-729. PMID: 35178738.
      Citations: 3     Fields:    Translation:HumansAnimals
    6. Yang C, Qiao T, Yu J, Wang H, Guo Y, Salameh J, Metterville J, Parsi S, Yusuf I, Brown RH, Cai H, Xu Z. Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice. PLoS One. 2022; 17(2):e0255710. PMID: 35113871.
      Citations: 11     Fields:    
    7. Zhao L, Wu X, Wang X, Duan C, Wang H, Punjabi A, Zhao Y, Zhang Y, Xu Z, Gao H, Han G. Development of Excipient-Free Freeze-Dryable Unimolecular Hyperstar Polymers for Efficient siRNA Silencing. ACS Macro Lett. 2017 Jul 18; 6(7):700-704. PMID: 35650873.
      Citations:    Fields:    
    8. Yang C, Danielson EW, Qiao T, Metterville J, Brown RH, Landers JE, Xu Z. Mutant PFN1 causes ALS phenotypes and progressive motor neuron degeneration in mice by a gain of toxicity. Proc Natl Acad Sci U S A. 2016 10 11; 113(41):E6209-E6218. PMID: 27681617.
      Citations: 41     Fields:    Translation:HumansAnimalsCells
    9. Xu Z, Yang C. TDP-43-The key to understanding amyotrophic lateral sclerosis. Rare Dis. 2014; 2(1):e944443. PMID: 26942097.
    10. Zuoshang Xu Chunxing Yang. TDP-43 The key to understanding amyotrophic lateral sclerosis. Rare Diseases. 2014. View Publication.
    11. Yang B, Li S, Wang H, Guo Y, Gessler DJ, Cao C, Su Q, Kramer J, Zhong L, Ahmed SS, Zhang H, He R, Desrosiers RC, Brown R, Xu Z, Gao G. Global CNS transduction of adult mice by intravenously delivered rAAVrh.8 and rAAVrh.10 and nonhuman primates by rAAVrh.10. Mol Ther. 2014 Jul; 22(7):1299-1309. PMID: 24781136.
      Citations: 117     Fields:    Translation:AnimalsCells
    12. Yang C, Wang H, Qiao T, Yang B, Aliaga L, Qiu L, Tan W, Salameh J, McKenna-Yasek DM, Smith T, Peng L, Moore MJ, Brown RH, Cai H, Xu Z. Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2014 Mar 25; 111(12):E1121-9. PMID: 24616503.
      Citations: 94     Fields:    Translation:Animals
    13. Cheng W, Ip YT, Xu Z. Gudu, an Armadillo repeat-containing protein, is required for spermatogenesis in Drosophila. Gene. 2013 Dec 01; 531(2):294-300. PMID: 24055424.
      Citations: 19     Fields:    Translation:Animals
    14. Broering TJ, Wang H, Boatright NK, Wang Y, Baptista K, Shayan G, Garrity KA, Kayatekin C, Bosco DA, Matthews CR, Ambrosino DM, Xu Z, Babcock GJ. Identification of human monoclonal antibodies specific for human SOD1 recognizing distinct epitopes and forms of SOD1. PLoS One. 2013; 8(4):e61210. PMID: 23613814.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    15. Qiu L, Qiao T, Beers M, Tan W, Wang H, Yang B, Xu Z. Widespread aggregation of mutant VAPB associated with ALS does not cause motor neuron degeneration or modulate mutant SOD1 aggregation and toxicity in mice. Mol Neurodegener. 2013 Jan 03; 8:1. PMID: 23281774.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    16. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23; 488(7412):499-503. PMID: 22801503.
      Citations: 288     Fields:    Translation:HumansAnimalsCells
    17. Xu ZS. Does a loss of TDP-43 function cause neurodegeneration? Mol Neurodegener. 2012 Jun 14; 7:27. PMID: 22697423.
      Citations: 48     Fields:    Translation:HumansAnimals
    18. Zhang H, Yang B, Mu X, Ahmed SS, Su Q, He R, Wang H, Mueller C, Sena-Esteves M, Brown R, Xu Z, Gao G. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol Ther. 2011 Aug; 19(8):1440-8. PMID: 21610699.
      Citations: 163     Fields:    Translation:AnimalsCells
    19. Qiu L, Rivera-P?rez JA, Xu Z. A non-specific effect associated with conditional transgene expression based on Cre-loxP strategy in mice. PLoS One. 2011 May 10; 6(5):e18778. PMID: 21572998.
      Citations: 15     Fields:    Translation:Animals
    20. Yang C, Qiu L, Xu Z. Specific gene silencing using RNAi in cell culture. Methods Mol Biol. 2011; 793:457-77. PMID: 21913119.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    21. Yang C, Tan W, Whittle C, Qiu L, Cao L, Akbarian S, Xu Z. The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS One. 2010 Dec 31; 5(12):e15878. PMID: 21209826.
      Citations: 96     Fields:    Translation:HumansAnimalsCells
    22. Wu R, Wang H, Xia X, Zhou H, Liu C, Castro M, Xu Z. Nerve injection of viral vectors efficiently transfers transgenes into motor neurons and delivers RNAi therapy against ALS. Antioxid Redox Signal. 2009 Jul; 11(7):1523-34. PMID: 19344276.
      Citations: 13     Fields:    Translation:AnimalsCells
    23. Qiu L, Wang H, Xia X, Zhou H, Xu Z. A construct with fluorescent indicators for conditional expression of miRNA. BMC Biotechnol. 2008 Oct 07; 8:77. PMID: 18840295.
      Citations: 28     Fields:    
    24. Wang H, Ghosh A, Baigude H, Yang CS, Qiu L, Xia X, Zhou H, Rana TM, Xu Z. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression. J Biol Chem. 2008 Jun 06; 283(23):15845-52. PMID: 18367449.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    25. Zou T, Ilangovan R, Yu F, Xu Z, Zhou J. SMN protects cells against mutant SOD1 toxicity by increasing chaperone activity. Biochem Biophys Res Commun. 2007 Dec 28; 364(4):850-5. PMID: 17964281.
      Citations: 18     Fields:    Translation:AnimalsCells
    26. Schwarz DS, Ding H, Kennington L, Moore JT, Schelter J, Burchard J, Linsley PS, Aronin N, Xu Z, Zamore PD. Designing siRNA that distinguish between genes that differ by a single nucleotide. PLoS Genet. 2006 Sep 08; 2(9):e140. PMID: 16965178.
      Citations: 123     Fields:    Translation:HumansAnimalsCells
    27. Xia X, Zhou H, Huang Y, Xu Z. Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo. Neurobiol Dis. 2006 Sep; 23(3):578-86. PMID: 16857362.
      Citations: 42     Fields:    Translation:HumansAnimalsCells
    28. Xia XG, Zhou H, Xu Z. Multiple shRNAs expressed by an inducible pol II promoter can knock down the expression of multiple target genes. Biotechniques. 2006 Jul; 41(1):64-8. PMID: 16869515.
      Citations: 30     Fields:    Translation:HumansAnimalsCells
    29. Xia XG, Zhou H, Xu Z. Transgenic RNAi: Accelerating and expanding reverse genetics in mammals. Transgenic Res. 2006 Jun; 15(3):271-5. PMID: 16779643.
      Citations: 5     Fields:    Translation:AnimalsCells
    30. Schonhoff CM, Matsuoka M, Tummala H, Johnson MA, Estev?z AG, Wu R, Kamaid A, Ricart KC, Hashimoto Y, Gaston B, Macdonald TL, Xu Z, Mannick JB. S-nitrosothiol depletion in amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006 Feb 14; 103(7):2404-9. PMID: 16461917.
      Citations: 39     Fields:    Translation:HumansAnimalsCells
    31. Xia XG, Zhou H, Samper E, Melov S, Xu Z. Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of the gene knockout in mice. PLoS Genet. 2006 Jan; 2(1):e10. PMID: 16450009.
      Citations: 34     Fields:    Translation:AnimalsCells
    32. Tiwari A, Xu Z, Hayward LJ. Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis. J Biol Chem. 2005 Aug 19; 280(33):29771-9. PMID: 15958382.
      Citations: 50     Fields:    Translation:HumansAnimalsCells
    33. Zhou H, Xia XG, Xu Z. An RNA polymerase II construct synthesizes short-hairpin RNA with a quantitative indicator and mediates highly efficient RNAi. Nucleic Acids Res. 2005 Apr 01; 33(6):e62. PMID: 15805121.
      Citations: 61     Fields:    Translation:HumansCells
    34. Tummala H, Jung C, Tiwari A, Higgins CM, Hayward LJ, Xu Z. Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosis. J Biol Chem. 2005 May 06; 280(18):17725-31. PMID: 15753080.
      Citations: 17     Fields:    Translation:HumansAnimals
    35. Xia XG, Zhou H, Xu Z. Promises and challenges in developing RNAi as a research tool and therapy for neurodegenerative diseases. Neurodegener Dis. 2005; 2(3-4):220-31. PMID: 16909029.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    36. Xia XG, Zhou H, Zhou S, Yu Y, Wu R, Xu Z. An RNAi strategy for treatment of amyotrophic lateral sclerosis caused by mutant Cu,Zn superoxide dismutase. J Neurochem. 2005 Jan; 92(2):362-7. PMID: 15663483.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    37. Xu Z, Jung C, Higgins C, Levine J, Kong J. Mitochondrial degeneration in amyotrophic lateral sclerosis. J Bioenerg Biomembr. 2004 Aug; 36(4):395-9. PMID: 15377878.
      Citations: 24     Fields:    Translation:AnimalsCells
    38. Schwarz DS, Hutv?gner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003 Oct 17; 115(2):199-208. PMID: 14567917.
      Citations: 1086     Fields:    Translation:AnimalsCells
    39. Xia XG, Zhou H, Ding H, Affar el B, Shi Y, Xu Z. An enhanced U6 promoter for synthesis of short hairpin RNA. Nucleic Acids Res. 2003 Sep 01; 31(17):e100. PMID: 12930974.
      Citations: 38     Fields:    Translation:HumansCells
    40. Ding H, Schwarz DS, Keene A, Affar el B, Fenton L, Xia X, Shi Y, Zamore PD, Xu Z. Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis. Aging Cell. 2003 08; 2(4):209-17. PMID: 12934714.
      Citations: 56     Fields:    Translation:HumansAnimals
    41. Higgins CM, Jung C, Xu Z. ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci. 2003 Jul 15; 4:16. PMID: 12864925.
      Citations: 97     Fields:    Translation:HumansAnimalsCells
    42. Zhang Z, Casey DM, Julien JP, Xu Z. Normal dendritic arborization in spinal motoneurons requires neurofilament subunit L. J Comp Neurol. 2002 Aug 19; 450(2):144-52. PMID: 12124759.
      Citations: 12     Fields:    Translation:AnimalsCells
    43. Jung C, Higgins CM, Xu Z. A quantitative histochemical assay for activities of mitochondrial electron transport chain complexes in mouse spinal cord sections. J Neurosci Methods. 2002 Mar 15; 114(2):165-72. PMID: 11856567.
      Citations: 33     Fields:    Translation:AnimalsCells
    44. Higgins CM, Jung C, Ding H, Xu Z. Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS. J Neurosci. 2002 Mar 15; 22(6):RC215. PMID: 11886899.
      Citations: 92     Fields:    Translation:HumansAnimalsCells
    45. Xu Z, Tung VW. Temporal and spatial variations in slow axonal transport velocity along peripheral motoneuron axons. Neuroscience. 2001; 102(1):193-200. PMID: 11226683.
      Citations: 14     Fields:    Translation:AnimalsCells
    46. Xu Z. Mechanism and treatment of motoneuron degeneration in ALS: what have SOD1 mutants told us? Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Sep; 1(4):225-34. PMID: 11465016.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    47. Xu Z, Tung VW. Overexpression of neurofilament subunit M accelerates axonal transport of neurofilaments. Brain Res. 2000 Jun 02; 866(1-2):326-32. PMID: 10825509.
      Citations: 10     Fields:    Translation:AnimalsCells
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