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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
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - School of Medicine
    DepartmentNeurology

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    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


    Collapse Biography 
    Collapse education and training
    State University of New York, Binghamton, Binghamton, NY, United StatesBSChemistry
    Brandeis University, Waltham, MA, United StatesPHDBioorganic Chemistry

    Collapse Overview 
    Collapse overview


    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



    Collapse Rotation Projects


    Rotation Projects:



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




    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.
    List All   |   Timeline
    1. Medinas DB, Rozas P, Martínez Traub F, Woehlbier U, Brown RH, Bosco DA, Hetz C. Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2018 Jul 23. PMID: 30038021.
      View in: PubMed
    2. Sama RR, Fallini C, Gatto R, McKeon JE, Song Y, Rotunno MS, Penaranda S, Abdurakhmanov I, Landers JE, Morfini G, Brady ST, Bosco DA. ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation. Sci Rep. 2017 Dec; 7(1):115. PMID: 28273913.
      View in: PubMed
    3. Peters OM, Cabrera GT, Tran H, Gendron TF, McKeon JE, Metterville J, Weiss A, Wightman N, Salameh J, Kim J, Sun H, Boylan KB, Dickson D, Kennedy Z, Lin Z, Zhang YJ, Daughrity L, Jung C, Gao FB, Sapp PC, Horvitz HR, Bosco DA, Brown SP, de Jong P, Petrucelli L, Mueller C, Brown RH. Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice. Neuron. 2015 Dec 02; 88(5):902-9. PMID: 26637797.
      View in: PubMed
    4. Boopathy S, Silvas TV, Tischbein M, Jansen S, Shandilya SM, Zitzewitz JA, Landers JE, Goode BL, Schiffer CA, Bosco DA. Structural basis for mutation-induced destabilization of profilin 1 in ALS. Proc Natl Acad Sci U S A. 2015 Jun 30; 112(26):7984-9. PMID: 26056300.
      View in: PubMed
    5. Matus S, Bosco DA, Hetz C. Autophagy meets fused in sarcoma-positive stress granules. Neurobiol Aging. 2014 Dec; 35(12):2832-5. PMID: 25444610.
      View in: PubMed
    6. Rotunno MS, Auclair JR, Maniatis S, Shaffer SA, Agar J, Bosco DA. Identification of a misfolded region in superoxide dismutase 1 that is exposed in amyotrophic lateral sclerosis. J Biol Chem. 2014 Oct 10; 289(41):28527-38. PMID: 25164820.
      View in: PubMed
    7. Sama RR, Ward CL, Bosco DA. Functions of FUS/TLS from DNA repair to stress response: implications for ALS. ASN Neuro. 2014 Jun 01; 6(4). PMID: 25289647.
      View in: PubMed
    8. 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. PMID: 24634066.
      View in: PubMed
    9. Rotunno MS, Bosco DA. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis. Front Cell Neurosci. 2013 Dec 16; 7:253. PMID: 24379756.
      View in: PubMed
    10. 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. PMID: 23625794.
      View in: PubMed
    11. 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 Aug 31; 8:30. PMID: 24090136.
      View in: PubMed
    12. 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. PMID: 23927036.
      View in: PubMed
    13. 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. PMID: 23776455.
      View in: PubMed
    14. 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.
      View in: PubMed
    15. 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. PMID: 22023190.
      View in: PubMed
    16. 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. PMID: 21541368.
      View in: PubMed
    17. Bosco DA, Landers JE. Genetic determinants of amyotrophic lateral sclerosis as therapeutic targets. CNS Neurol Disord Drug Targets. 2010 Dec; 9(6):779-90. PMID: 20942785.
      View in: PubMed
    18. 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. PMID: 20953194.
      View in: PubMed
    19. 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. PMID: 20708627.
      View in: PubMed
    20. 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. PMID: 20699327.
      View in: PubMed
    21. 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. PMID: 20582942.
      View in: PubMed
    22. 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. PMID: 19828789.
      View in: PubMed
    23. 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. PMID: 19525973.
      View in: PubMed
    24. 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. PMID: 17316687.
      View in: PubMed
    25. 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. PMID: 16981677.
      View in: PubMed
    26. 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. PMID: 16565714.
      View in: PubMed
    27. 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. PMID: 11929983.
      View in: PubMed
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