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    Daryl A Bosco PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurology
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street, AS6-1057
    Worcester MA 01605
    Phone774-455-3745
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Biography

        Daryl Bosco received her Ph.D. (bio-organic chemistry) in 2003 from Brandeis University, where she used NMR spectroscopy to study enzyme dynamics. From 2003-2005, Dr. Bosco was a post-doctoral fellow in the lab of Jeffery W. Kelly at the Scripps Research Institute, where she studied the effect of oxidative cholesterol metabolites on the mis-folding of alpha-synuclein, a Parkinson's disease-associated protein. Prior to joining the faculty at UMMS in 2008, Dr. Bosco was an Instructor of Neurology at Harvard Medical School and worked on various aspects of ALS in the Cecile B. Day lab directed by Dr. Robert H. Brown, Jr. at the Massachusetts General Hospital.

        Research

        Our lab is investigating the pathogenic mechanisms of ALS-associated proteins SOD1, FUS/TLS, profilin-1 and TDP-43.  ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease, is a fatal neurodegenerative disorder that targets motor neurons.  Motor neuron death culminates in paralysis and eventual death, usually 2-3 years after symptom onset.  To date, there is no cure or effective therapy for ALS.  Our ultimate goal is to translate our basic-research findings into therapies for this devastating disease.   We use a multidisciplinary approach involving biochemistry, cell biology (including iPS cell technology), biophysics and in vivo model systems for our investigations. See our lab webpage for more information on Research Projects: boscolab.com



        Rotation Projects

        Rotation Projects:

        See our lab webpage for more information on Research Projects: boscolab.com



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Auclair JR, Salisbury JP, Johnson JL, Petsko GA, Ringe D, Bosco DA, Agar NY, Santagata S, Durham HD, Agar JN. Artifacts to avoid while taking advantage of top-down mass spectrometry based detection of protein S-thiolation. Proteomics. 2014 May; 14(10):1152-7.
          View in: PubMed
        2. Rotunno MS, Bosco DA. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis. Front Cell Neurosci. 2013; 7:253.
          View in: PubMed
        3. Sama RR, Ward CL, Kaushansky LJ, Lemay N, Ishigaki S, Urano F, Bosco DA. FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress. J Cell Physiol. 2013 Nov; 228(11):2222-31.
          View in: PubMed
        4. Baron DM, Kaushansky LJ, Ward CL, Sama RR, Chian RJ, Boggio KJ, Quaresma AJ, Nickerson JA, Bosco DA. Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics. Mol Neurodegener. 2013; 8(1):30.
          View in: PubMed
        5. Auclair JR, Johnson JL, Liu Q, Salisbury JP, Rotunno MS, Petsko GA, Ringe D, Brown RH, Bosco DA, Agar JN. Post-translational modification by cysteine protects cu/zn-superoxide dismutase from oxidative damage. Biochemistry. 2013 Sep 10; 52(36):6137-44.
          View in: PubMed
        6. Morfini GA, Bosco DA, Brown H, Gatto R, Kaminska A, Song Y, Molla L, Baker L, Marangoni MN, Berth S, Tavassoli E, Bagnato C, Tiwari A, Hayward LJ, Pigino GF, Watterson DM, Huang CF, Banker G, Brown RH, Brady ST. Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase. PLoS One. 2013; 8(6):e65235.
          View in: PubMed
        7. 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.
          View in: PubMed
        8. van Blitterswijk M, Gulati S, Smoot E, Jaffa M, Maher N, Hyman BT, Ivinson AJ, Scherzer CR, Schoenfeld DA, Cudkowicz ME, Brown RH, Bosco DA. Anti-superoxide dismutase antibodies are associated with survival in patients with sporadic amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011 Nov; 12(6):430-8.
          View in: PubMed
        9. Ju S, Tardiff DF, Han H, Divya K, Zhong Q, Maquat LE, Bosco DA, Hayward LJ, Brown RH, Lindquist S, Ringe D, Petsko GA. A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol. 2011 Apr; 9(4):e1001052.
          View in: PubMed
        10. Bosco DA, Landers JE. Genetic determinants of amyotrophic lateral sclerosis as therapeutic targets. CNS Neurol Disord Drug Targets. 2010 Dec; 9(6):779-90.
          View in: PubMed
        11. Bosco DA, Morfini G, Karabacak NM, Song Y, Gros-Louis F, Pasinelli P, Goolsby H, Fontaine BA, Lemay N, McKenna-Yasek D, Frosch MP, Agar JN, Julien JP, Brady ST, Brown RH. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat Neurosci. 2010 Nov; 13(11):1396-403.
          View in: PubMed
        12. Bosco DA, Eisenmesser EZ, Clarkson MW, Wolf-Watz M, Labeikovsky W, Millet O, Kern D. Dissecting the microscopic steps of the cyclophilin A enzymatic cycle on the biological HIV-1 capsid substrate by NMR. J Mol Biol. 2010 Nov 12; 403(5):723-38.
          View in: PubMed
        13. Bosco DA, Lemay N, Ko HK, Zhou H, Burke C, Kwiatkowski TJ, Sapp P, McKenna-Yasek D, Brown RH, Hayward LJ. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum Mol Genet. 2010 Nov 1; 19(21):4160-75.
          View in: PubMed
        14. Ticozzi N, LeClerc AL, Keagle PJ, Glass JD, Wills AM, van Blitterswijk M, Bosco DA, Rodriguez-Leyva I, Gellera C, Ratti A, Taroni F, McKenna-Yasek D, Sapp PC, Silani V, Furlong CE, Brown RH, Landers JE. Paraoxonase gene mutations in amyotrophic lateral sclerosis. Ann Neurol. 2010 Jul; 68(1):102-7.
          View in: PubMed
        15. Morfini GA, Burns M, Binder LI, Kanaan NM, LaPointe N, Bosco DA, Brown RH, Brown H, Tiwari A, Hayward L, Edgar J, Nave KA, Garberrn J, Atagi Y, Song Y, Pigino G, Brady ST. Axonal transport defects in neurodegenerative diseases. J Neurosci. 2009 Oct 14; 29(41):12776-86.
          View in: PubMed
        16. Gao J, Bosco DA, Powers ET, Kelly JW. Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins. Nat Struct Mol Biol. 2009 Jul; 16(7):684-90.
          View in: PubMed
        17. Labeikovsky W, Eisenmesser EZ, Bosco DA, Kern D. Structure and dynamics of pin1 during catalysis by NMR. J Mol Biol. 2007 Apr 13; 367(5):1370-81.
          View in: PubMed
        18. Bieschke J, Zhang Q, Bosco DA, Lerner RA, Powers ET, Wentworth P, Kelly JW. Small molecule oxidation products trigger disease-associated protein misfolding. Acc Chem Res. 2006 Sep; 39(9):611-9.
          View in: PubMed
        19. Bosco DA, Fowler DM, Zhang Q, Nieva J, Powers ET, Wentworth P, Lerner RA, Kelly JW. Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization. Nat Chem Biol. 2006 May; 2(5):249-53.
          View in: PubMed
        20. Bosco DA, Eisenmesser EZ, Pochapsky S, Sundquist WI, Kern D. Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proc Natl Acad Sci U S A. 2002 Apr 16; 99(8):5247-52.
          View in: PubMed
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