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Michael R Volkert PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentMicrobiology and Physiological Systems
AddressUniversity of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-2314
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMolecular Genetics and Microbiology

    InstitutionUMMS - 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 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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    1. Yu L, Rege M, Peterson CL, Volkert MR. RNA polymerase II depletion promotes transcription of alternative mRNA species. BMC Mol Biol. 2016 Aug 30; 17(1):20. PMID: 27578267.
      View in: PubMed
    2. 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.
      View in: PubMed
    3. 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.
      View in: PubMed
    4. 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 ß-1b. J Interferon Cytokine Res. 2015 Mar; 35(3):186-99. PMID: 25330068.
      View in: PubMed
    5. 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.
      View in: PubMed
    6. Yu L, Volkert MR. UV damage regulates alternative polyadenylation of the RPB2 gene in yeast. Nucleic Acids Res. 2013 Mar 1; 41(5):3104-14. PMID: 23355614.
      View in: PubMed
    7. 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.
      View in: PubMed
    8. 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 5; 10(9):934-41. PMID: 21788159.
      View in: PubMed
    9. 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.
      View in: PubMed
    10. 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.
      View in: PubMed
    11. 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.
      View in: PubMed
    12. Matijasevic Z, Volkert MR. Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide. DNA Repair (Amst). 2007 Jun 1; 6(6):733-41. PMID: 17292678.
      View in: PubMed
    13. 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.
      View in: PubMed
    14. 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.
      View in: PubMed
    15. 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.
      View in: PubMed
    16. 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.
      View in: PubMed
    17. 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.
      View in: PubMed
    18. 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.
      View in: PubMed
    19. Volkert MR, Landini P. Transcriptional responses to DNA damage. Curr Opin Microbiol. 2001 Apr; 4(2):178-85. PMID: 11282474.
      View in: PubMed
    20. 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.
      View in: PubMed
    21. Landini P, Volkert MR. Regulatory responses of the adaptive response to alkylation damage: a simple regulon with complex regulatory features. J Bacteriol. 2000 Dec; 182(23):6543-9. PMID: 11073893.
      View in: PubMed
    22. Dunman PM, Ren L, Rahman MS, Palejwala VA, Murphy HS, Volkert MR, Humayun MZ. Escherichia coli cells defective for the recN gene display constitutive elevation of mutagenesis at 3,N(4)-ethenocytosine via an SOS-induced mechanism. Mol Microbiol. 2000 Aug; 37(3):680-6. PMID: 10931361.
      View in: PubMed
    23. Landini P, Bown JA, Volkert MR, Busby SJ. Ada protein-RNA polymerase sigma subunit interaction and alpha subunit-promoter DNA interaction are necessary at different steps in transcription initiation at the Escherichia coli Ada and aidB promoters. J Biol Chem. 1998 May 22; 273(21):13307-12. PMID: 9582376.
      View in: PubMed
    24. Adam E, Volkert MR, Blot M. Cytochrome c biogenesis is involved in the transposon Tn5-mediated bleomycin resistance and the associated fitness effect in Escherichia coli. Mol Microbiol. 1998 Apr; 28(1):15-24. PMID: 9593293.
      View in: PubMed
    25. Landini P, Gaal T, Ross W, Volkert MR. The RNA polymerase alpha subunit carboxyl-terminal domain is required for both basal and activated transcription from the alkA promoter. J Biol Chem. 1997 Jun 20; 272(25):15914-9. PMID: 9188491.
      View in: PubMed
    26. Landini P, Hajec LI, Nguyen LH, Burgess RR, Volkert MR. The leucine-responsive regulatory protein (Lrp) acts as a specific repressor for sigma s-dependent transcription of the Escherichia coli aidB gene. Mol Microbiol. 1996 Jun; 20(5):947-55. PMID: 8809748.
      View in: PubMed
    27. Landini P, Volkert MR. RNA polymerase alpha subunit binding site in positively controlled promoters: a new model for RNA polymerase-promoter interaction and transcriptional activation in the Escherichia coli ada and aidB genes. EMBO J. 1995 Sep 1; 14(17):4329-35. PMID: 7556074.
      View in: PubMed
    28. Landini P, Volkert MR. Transcriptional activation of the Escherichia coli adaptive response gene aidB is mediated by binding of methylated Ada protein. Evidence for a new consensus sequence for Ada-binding sites. J Biol Chem. 1995 Apr 7; 270(14):8285-9. PMID: 7713936.
      View in: PubMed
    29. Volkert MR, Hajec LI, Matijasevic Z, Fang FC, Prince R. Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene. J Bacteriol. 1994 Dec; 176(24):7638-45. PMID: 8002588.
      View in: PubMed
    30. Landini P, Hajec LI, Volkert MR. Structure and transcriptional regulation of the Escherichia coli adaptive response gene aidB. J Bacteriol. 1994 Nov; 176(21):6583-9. PMID: 7961409.
      View in: PubMed
    31. Volkert MR, Loewen PC, Switala J, Crowley D, Conley M. The delta (argF-lacZ)205(U169) deletion greatly enhances resistance to hydrogen peroxide in stationary-phase Escherichia coli. J Bacteriol. 1994 Mar; 176(5):1297-302. PMID: 8113168.
      View in: PubMed
    32. Matijasevic Z, Hajec LI, Volkert MR. Anaerobic induction of the alkylation-inducible Escherichia coli aidB gene involves genes of the cysteine biosynthetic pathway. J Bacteriol. 1992 Mar; 174(6):2043-6. PMID: 1312537.
      View in: PubMed
    33. Volkert MR, Hajec LI. Molecular analysis of the aidD6::Mu d1 (bla lac) fusion mutation of Escherichia coli K12. Mol Gen Genet. 1991 Oct; 229(2):319-23. PMID: 1921981.
      View in: PubMed
    34. Volkert MR, Gately FH, Hajec LI. Expression of DNA damage-inducible genes of Escherichia coli upon treatment with methylating, ethylating and propylating agents. Mutat Res. 1989 Mar; 217(2):109-15. PMID: 2493133.
      View in: PubMed
    35. Volkert MR, Hajec LI, Nguyen DC. Induction of the alkylation-inducible aidB gene of Escherichia coli by anaerobiosis. J Bacteriol. 1989 Feb; 171(2):1196-8. PMID: 2492508.
      View in: PubMed
    36. Volkert MR. Altered induction of the adaptive response to alkylation damage in Escherichia coli recF mutants. J Bacteriol. 1989 Jan; 171(1):99-103. PMID: 2536670.
      View in: PubMed
    37. Fram RJ, Crockett J, Volkert MR. Gene expression caused by alkylating agents and cis-diamminedichloroplatinum(II) in Escherichia coli. Cancer Res. 1988 Sep 1; 48(17):4823-6. PMID: 3044578.
      View in: PubMed
    38. Poteete AR, Volkert MR. Activation of recF-dependent recombination in Escherichia coli by bacteriophage lambda- and P22-encoded functions. J Bacteriol. 1988 Sep; 170(9):4379-81. PMID: 2842317.
      View in: PubMed
    39. Fram RJ, Marinus MG, Volkert MR. Gene expression in E. coli after treatment with streptozotocin. Mutat Res. 1988 Mar; 198(1):45-51. PMID: 2965298.
      View in: PubMed
    40. Volkert MR. Adaptive response of Escherichia coli to alkylation damage. Environ Mol Mutagen. 1988; 11(2):241-55. PMID: 3278898.
      View in: PubMed
    41. Volkert MR, Hartke MA. Effects of the Escherichia coli recF suppressor mutation, recA801, on recF-dependent DNA-repair associated phenomena. Mutat Res. 1987 Nov; 184(3):181-6. PMID: 2823130.
      View in: PubMed
    42. Volkert MR, Nguyen DC, Beard KC. Escherichia coli gene induction by alkylation treatment. Genetics. 1986 Jan; 112(1):11-26. PMID: 3080354.
      View in: PubMed
    43. Volkert MR, Margossian LJ, Clark AJ. Two-component suppression of recF143 by recA441 in Escherichia coli K-12. J Bacteriol. 1984 Nov; 160(2):702-5. PMID: 6094485.
      View in: PubMed
    44. Volkert MR, Nguyen DC. Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents. Proc Natl Acad Sci U S A. 1984 Jul; 81(13):4110-4. PMID: 6330740.
      View in: PubMed
    45. Volkert MR, Hartke MA. Suppression of Escherichia coli recF mutations by recA-linked srfA mutations. J Bacteriol. 1984 Feb; 157(2):498-506. PMID: 6363387.
      View in: PubMed
    46. Clark AJ, Volkert MR, Margossian LJ, Nagaishi H. Effects of a recA operator mutation on mutant phenotypes conferred by lexA and recF mutations. Mutat Res. 1982 Nov; 106(1):11-26. PMID: 6219286.
      View in: PubMed
    47. Uhlin BE, Volkert MR, Clark AJ, Sancar A, Rupp WD. Nucleotide sequence of a recA operator mutation. LexA/operator-repressor binding/inducible repair. Mol Gen Genet. 1982; 185(2):251-4. PMID: 6953307.
      View in: PubMed
    48. Witkin EM, McCall JO, Volkert MR, Wermundsen IE. Constitutive expression of SOS functions and modulation of mutagenesis resulting from resolution of genetic instability at or near the recA locus of Escherichia coli. Mol Gen Genet. 1982; 185(1):43-50. PMID: 6211591.
      View in: PubMed
    49. Volkert MR, Margossian LJ, Clark AJ. Evidence that rnmB is the operator of the Escherichia coli recA gene. Proc Natl Acad Sci U S A. 1981 Mar; 78(3):1786-90. PMID: 7015345.
      View in: PubMed
    50. Volkert MR, Spencer DF, Clark AJ. Indirect and intragenic suppression of the lexA102 mutation in E. coli B/r. Mol Gen Genet. 1979; 177(1):129-37. PMID: 395409.
      View in: PubMed
    51. Clark AJ, Volkert MR, Margossian LJ. A role for recF in repair of UV damage to DNA. Cold Spring Harb Symp Quant Biol. 1979; 43 Pt 2:887-92. PMID: 385232.
      View in: PubMed
    52. Volkert MR, George DL, Witkin EM. Partial suppression of the LexA phenotype by mutations (rnm) which restore ultraviolet resistance but not ultraviolet mutability to Escherichia coli B/r uvr A lexA. Mutat Res. 1976 Jul; 36(1):17-28. PMID: 781527.
      View in: PubMed
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