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Michael R Volkert PhD

TitleProfessor Emeritus
InstitutionUMass Chan Medical School
DepartmentMicrobiology and Physiological Systems
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-2314
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentImmunology and Microbiology Program

    InstitutionUMass Chan Programs, Centers and Institutes
    DepartmentBacterial Genetics and Pathogenesis


    Collapse Biography 
    Collapse education and training
    University of Wisconsin, Madison, Madison, WI, United StatesBSBacteriology
    Iowa State University, Ames, IA, United StatesMSBacteriology
    Rutgers University- New Brunswick, New Brunswick, NJ, United StatesPH DMicroBiology

    Collapse Overview 
    Collapse Summary
    Focus: We are currently conducting gene therapy experiments to prevent neurodegeneration using an adeno-associated viral vector (AAV) that expresses the human OXR1 gene. Initial experiments demonstrate that elevated expression of OXR1 increases cellular resistance to oxidative stress and AAV8-hOXR1 delays degeneration of the photoreceptor neurons of the retina.
    Collapse overview

    Oxidative stress is a common feature of most retinal and neurodegenerative disease and a major factor leading to retinal and neural cell death. My laboratory studies the OXR1 family of oxidative stress resistance genes and their roles in preventing neurodegenerative diseases. Our projects are to test OXR1 gene therapy and its ability to prevent or delay retinal degeneration and preserve vision. We are also exploring the molecular mechanisms responsible OXR1 mediated neuroprotection.

    In collaboration with the laboratory of Hemant Khanna (UMass Medical School Dept. of Ophthalmology and Visual Sciences and the Horae Gene Therapy Center) we are testing the ability of OXR1 to delay loss of visual function in mouse models of several retinal degenerative diseases.

    Depletion or loss of OXR1 causes cells to become very sensitive to oxidative stress and its over expression results in levels of resistance that are much greater than normal cells. OXR1 depletion has been observed in several mouse models of retinal degenerative diseases. Thus, we expect that restoring high level OXR1 expression will protect the retinal neurons from oxidative stress induced death. We have also found that increasing OXR1 expression in cells that have normal levels of OXR1 greatly enhances their resistance to oxidative stress. Therefore, we predict that high-level expression of OXR1 will increase oxidative stress resistance and retinal degeneration in retinal diseases in which OXR1 is expressed at normal levels.

    We have tested this hypothesis in the rd1mouse model of retinal degeneration. We have shown a retention of visual function in eyes treated with a gene therapy vector that overexpresses OXR1 at a time when the contralateral eyes of the rd1mice have lost all visual function. The rd1 mouse model is a particularly aggressive and rapid onset of blindness model. We are now testing other mouse models such as the rhodopsin mutant mouse, which is a model for the most common form of retinitis pigmentosa in humans. This mouse has a much less aggressive and later onset of cone cell death than the rd1mouse model. This suggests that oxidative stress is much less severe than in the rd1 mutant mouse and therefore more amenable to the reduction in oxidative stress that results from OXR1 mediated gene therapy.

    We are also determining the molecular basis of OXR1 mediated neuroprotection in order to better understand how this gene functions. It is known that OXR1 is critical for the prevention of oxidative stress induced neurodegeneration. It has also been shown to function as a regulatory element that controls the expression of a number of transcriptional regulatory elements that control the cells’ responses to oxidative stress, apoptosis, the cell cycle, and DNA repair. We are determining the gene expression pattern changes that occur when OXR1 is overexpressed and what the roles of specific isoforms are and how they differ from one another in the responses they generate and the level of oxidative stress resistance they confer.

     


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    Collapse Bibliographic 
    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. Volkert MR. Remembering Evelyn M. Witkin (1921-2023) and the SOS Response. Proc Natl Acad Sci U S A. 2023 Sep 26; 120(39):e2314904120. PMID: 37722041.
      Citations:    Fields:    
    2. Sahu B, Leon LM, Zhang W, Puranik N, Periasamy R, Khanna H, Volkert M. Oxidative Stress Resistance 1 Gene Therapy Retards Neurodegeneration in the rd1 Mutant Mouse Model of Retinopathy. Invest Ophthalmol Vis Sci. 2021 09 02; 62(12):8. PMID: 34505865.
      Citations: 3     Fields:    Translation:HumansAnimalsCells
    3. Volkert MR, Crowley DJ. Preventing Neurodegeneration by Controlling Oxidative Stress: The Role of OXR1. Front Neurosci. 2020; 14:611904. PMID: 33384581.
      Citations:    
    4. Vishwakarma S, Gupta RK, Jakati S, Tyagi M, Pappuru RR, Reddig K, Hendricks G, Volkert MR, Khanna H, Chhablani J, Kaur I. Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation. Antioxidants (Basel). 2020 Jul 23; 9(8). PMID: 32717933.
      Citations:    
    5. Yu L, Rege M, Peterson CL, Volkert MR. RNA polymerase II depletion promotes transcription of alternative mRNA species. BMC Mol Biol. 2016 08 30; 17(1):20. PMID: 27578267.
      Citations: 4     Fields:    Translation:AnimalsCells
    6. Yu L, Ma H, Ji X, Volkert MR. The Sub1 nuclear protein protects DNA from oxidative damage. Mol Cell Biochem. 2016 Jan; 412(1-2):165-71. PMID: 26708217.
      Citations: 9     Fields:    Translation:Humans
    7. Sweasy JB, Lieberman HB, Volkert M, George D. Evelyn Witkin and the coordinated response to DNA damage. DNA Repair (Amst). 2015 Nov; 35:154-5. PMID: 26529061.
      Citations:    Fields:    Translation:Cells
    8. Yu L, Croze E, Yamaguchi KD, Tran T, Reder AT, Litvak V, Volkert MR. Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon ?-1b. J Interferon Cytokine Res. 2015 Mar; 35(3):186-99. PMID: 25330068.
      Citations: 22     Fields:    Translation:HumansCells
    9. Yu L, Volkert MR. Differential requirement for SUB1 in chromosomal and plasmid double-strand DNA break repair. PLoS One. 2013; 8(3):e58015. PMID: 23554872.
      Citations: 10     Fields:    Translation:AnimalsCells
    10. Yu L, Volkert MR. UV damage regulates alternative polyadenylation of the RPB2 gene in yeast. Nucleic Acids Res. 2013 Mar 01; 41(5):3104-14. PMID: 23355614.
      Citations: 12     Fields:    Translation:AnimalsCells
    11. Murphy KC, Volkert MR. Structural/functional analysis of the human OXR1 protein: identification of exon 8 as the anti-oxidant encoding function. BMC Mol Biol. 2012 Aug 08; 13:26. PMID: 22873401.
      Citations: 17     Fields:    Translation:HumansCells
    12. Rippa V, Duilio A, di Pasquale P, Amoresano A, Landini P, Volkert MR. Preferential DNA damage prevention by the E. coli AidB gene: A new mechanism for the protection of specific genes. DNA Repair (Amst). 2011 Sep 05; 10(9):934-41. PMID: 21788159.
      Citations: 14     Fields:    Translation:Cells
    13. Rippa V, Amoresano A, Esposito C, Landini P, Volkert M, Duilio A. Specific DNA binding and regulation of its own expression by the AidB protein in Escherichia coli. J Bacteriol. 2010 Dec; 192(23):6136-42. PMID: 20889740.
      Citations: 7     Fields:    Translation:Cells
    14. Volkert MR, Wang JY, Elliott NA. A functional genomics approach to identify and characterize oxidation resistance genes. Methods Mol Biol. 2008; 477:331-42. PMID: 19082958.
      Citations: 5     Fields:    Translation:HumansCells
    15. Durand M, Kolpak A, Farrell T, Elliott NA, Shao W, Brown M, Volkert MR. The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins. BMC Cell Biol. 2007 Mar 28; 8:13. PMID: 17391516.
      Citations: 39     Fields:    Translation:HumansCells
    16. Matijasevic Z, Volkert MR. Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide. DNA Repair (Amst). 2007 Jun 01; 6(6):733-41. PMID: 17292678.
      Citations: 3     Fields:    Translation:AnimalsCells
    17. Liang X, Pickering MT, Cho NH, Chang H, Volkert MR, Kowalik TF, Jung JU. Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2. J Virol. 2006 Jun; 80(12):5862-74. PMID: 16731925.
      Citations: 36     Fields:    Translation:HumansAnimalsCells
    18. Wang JY, Sarker AH, Cooper PK, Volkert MR. The single-strand DNA binding activity of human PC4 prevents mutagenesis and killing by oxidative DNA damage. Mol Cell Biol. 2004 Jul; 24(13):6084-93. PMID: 15199162.
      Citations: 42     Fields:    Translation:HumansCells
    19. Elliott NA, Volkert MR. Stress induction and mitochondrial localization of Oxr1 proteins in yeast and humans. Mol Cell Biol. 2004 Apr; 24(8):3180-7. PMID: 15060142.
      Citations: 50     Fields:    Translation:HumansAnimalsCells
    20. Wyrzykowski J, Volkert MR. The Escherichia coli methyl-directed mismatch repair system repairs base pairs containing oxidative lesions. J Bacteriol. 2003 Mar; 185(5):1701-4. PMID: 12591888.
      Citations: 35     Fields:    Translation:Cells
    21. Li Q, Wright SE, Matijasevic Z, Chong W, Ludlum DB, Volkert MR. The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas. Carcinogenesis. 2003 Mar; 24(3):589-93. PMID: 12663522.
      Citations:    Fields:    Translation:HumansCells
    22. Bonanno K, Wyrzykowski J, Chong W, Matijasevic Z, Volkert MR. Alkylation resistance of E. coli cells expressing different isoforms of human alkyladenine DNA glycosylase (hAAG). DNA Repair (Amst). 2002 Jul 17; 1(7):507-16. PMID: 12509225.
      Citations: 6     Fields:    Translation:HumansCells
    23. Volkert MR, Landini P. Transcriptional responses to DNA damage. Curr Opin Microbiol. 2001 Apr; 4(2):178-85. PMID: 11282474.
      Citations: 9     Fields:    Translation:Cells
    24. Volkert MR, Elliott NA, Housman DE. Functional genomics reveals a family of eukaryotic oxidation protection genes. Proc Natl Acad Sci U S A. 2000 Dec 19; 97(26):14530-5. PMID: 11114193.
      Citations: 61     Fields:    Translation:HumansAnimalsCells
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