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Daryl A Bosco PhD

TitleProfessor
InstitutionUMass Chan Medical School
DepartmentNeurology
AddressUMass Chan Medical School
368 Plantation Street AS6-1057
Worcester MA 01605
Phone774-455-3745
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology

    InstitutionT.H. Chan School of Medicine
    DepartmentNeurology

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentNeuroscience

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentPostbaccalaureate Research Education Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science


    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 Summary
    Elucidating the factors involved in sporadic ALS and investigating protein misfunction associated with neurodegenerative disease.
    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.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    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. Arredondo C, Cefaliello C, Dyrda A, Jury N, Martinez P, Díaz I, Amaro A, Tran H, Morales D, Pertusa M, Stoica L, Fritz E, Corvalán D, Abarzúa S, Méndez-Ruette M, Fernández P, Rojas F, Kumar MS, Aguilar R, Almeida S, Weiss A, Bustos FJ, González-Nilo F, Otero C, Tevy MF, Bosco DA, Sáez JC, Kähne T, Gao FB, Berry JD, Nicholson K, Sena-Esteves M, Madrid R, Varela D, Montecino M, Brown RH, van Zundert B. Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons. Neuron. 2022 05 18; 110(10):1656-1670.e12. PMID: 35276083.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    2. Kahriman A, Bouley J, Bosco DA, Shazeeb MS, Henninger N. Differential association of baseline body weight and body-weight loss with neurological deficits, histology, and death after repetitive closed head traumatic brain injury. Neurosci Lett. 2022 02 06; 771:136430. PMID: 34973374.
      Citations:    Fields:    Translation:AnimalsCells
    3. Kahriman A, Bouley J, Smith TW, Bosco DA, Woerman AL, Henninger N. Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature. Acta Neuropathol Commun. 2021 06 29; 9(1):118. PMID: 34187585.
      Citations: 3     Fields:    Translation:HumansAnimals
    4. Schmidt EJ, Funes S, McKeon JE, Morgan BR, Boopathy S, O'Connor LC, Bilsel O, Massi F, Jégou A, Bosco DA. ALS-linked PFN1 variants exhibit loss and gain of functions in the context of formin-induced actin polymerization. Proc Natl Acad Sci U S A. 2021 06 08; 118(23). PMID: 34074767.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    5. Lin YC, Kumar MS, Ramesh N, Anderson EN, Nguyen AT, Kim B, Cheung S, McDonough JA, Skarnes WC, Lopez-Gonzalez R, Landers JE, Fawzi NL, Mackenzie IRA, Lee EB, Nickerson JA, Grunwald D, Pandey UB, Bosco DA. Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway. Nat Neurosci. 2021 08; 24(8):1077-1088. PMID: 34059832.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    6. Murtas G, Sacchi S, Kumar MS, Bosco DA, Pollegioni L. Is the primate-specific protein pLG72 affecting SOD1 functionality and superoxide formation? Free Radic Res. 2020 Jun; 54(6):419-430. PMID: 32623917.
      Citations: 1     Fields:    Translation:Humans
    7. Bartoletti M, Bosco DA, Da Cruz S, Lagier-Tourenne C, Liachko N, Markmiller S, Webster KM, Wharton KA. Phenotypic Suppression of ALS/FTD-Associated Neurodegeneration Highlights Mechanisms of Dysfunction. J Neurosci. 2019 10 16; 39(42):8217-8224. PMID: 31619490.
      Citations: 4     Fields:    Translation:HumansAnimals
    8. Baron DM, Matheny T, Lin YC, Leszyk JD, Kenna K, Gall KV, Santos DP, Tischbein M, Funes S, Hayward LJ, Kiskinis E, Landers JE, Parker R, Shaffer SA, Bosco DA. Quantitative proteomics identifies proteins that resist translational repression and become dysregulated in ALS-FUS. Hum Mol Genet. 2019 07 01; 28(13):2143-2160. PMID: 30806671.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    9. Tischbein M, Baron DM, Lin YC, Gall KV, Landers JE, Fallini C, Bosco DA. The RNA-binding protein FUS/TLS undergoes calcium-mediated nuclear egress during excitotoxic stress and is required for GRIA2 mRNA processing. J Biol Chem. 2019 06 28; 294(26):10194-10210. PMID: 31092554.
      Citations: 10     Fields:    Translation:HumansCells
    10. Bosco DA. Translation dysregulation in neurodegenerative disorders. Proc Natl Acad Sci U S A. 2018 12 18; 115(51):12842-12844. PMID: 30504142.
      Citations: 5     Fields:    Translation:HumansCells
    11. 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 08 07; 115(32):8209-8214. PMID: 30038021.
      Citations: 34     Fields:    Translation:HumansAnimalsCells
    12. 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 03 08; 7(1):115. PMID: 28273913.
      Citations: 20     Fields:    Translation:HumansAnimalsCells
    13. 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):902-909. PMID: 26637797.
      Citations: 133     Fields:    Translation:HumansAnimalsCells
    14. 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.
      Citations: 32     Fields:    Translation:HumansCells
    15. Ward CL, Boggio KJ, Johnson BN, Boyd JB, Douthwright S, Shaffer SA, Landers JE, Glicksman MA, Bosco DA. A loss of FUS/TLS function leads to impaired cellular proliferation. Cell Death Dis. 2014 Dec 11; 5:e1572. PMID: 25501833.
      Citations: 25     Fields:    Translation:HumansCells
    16. Matus S, Bosco DA, Hetz C. Autophagy meets fused in sarcoma-positive stress granules. Neurobiol Aging. 2014 Dec; 35(12):2832-2835. PMID: 25444610.
      Citations: 11     Fields:    Translation:HumansCells
    17. 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.
      Citations: 17     Fields:    Translation:HumansAnimalsCells
    18. 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.
      Citations: 53     Fields:    Translation:HumansAnimalsCells
    19. 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.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    20. 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.
      Citations:    
    21. 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.
      Citations: 73     Fields:    Translation:HumansAnimalsCells
    22. 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.
      Citations: 71     Fields:    Translation:HumansAnimalsCells
    23. 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.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    24. 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.
      Citations: 52     Fields:    Translation:AnimalsCells
    25. 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: 253     Fields:    Translation:HumansAnimalsCells
    26. 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.
      Citations: 10     Fields:    Translation:HumansAnimals
    27. 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.
      Citations: 117     Fields:    Translation:AnimalsCells
    28. Ticozzi N, Vance C, Leclerc AL, Keagle P, Glass JD, McKenna-Yasek D, Sapp PC, Silani V, Bosco DA, Shaw CE, Brown RH, Landers JE. Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. Am J Med Genet B Neuropsychiatr Genet. 2011 Apr; 156B(3):285-90. PMID: 21438137.
      Citations: 83     Fields:    Translation:HumansCells
    29. 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.
      Citations: 21     Fields:    Translation:Humans
    30. 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.
      Citations: 312     Fields:    Translation:HumansCells
    31. 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.
      Citations: 18     Fields:    Translation:HumansCells
    32. 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 01; 19(21):4160-75. PMID: 20699327.
      Citations: 257     Fields:    Translation:HumansAnimalsCells
    33. 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.
      Citations: 27     Fields:    Translation:HumansCells
    34. 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.
      Citations: 231     Fields:    Translation:HumansAnimalsCells
    35. 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.
      Citations: 60     Fields:    Translation:HumansCells
    36. Kwiatkowski TJ, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009 Feb 27; 323(5918):1205-8. PMID: 19251627.
      Citations: 1138     Fields:    Translation:HumansAnimalsCells
    37. 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.
      Citations: 38     Fields:    Translation:HumansCells
    38. 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.
      Citations: 25     Fields:    Translation:HumansCells
    39. 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.
      Citations: 128     Fields:    Translation:HumansCells
    40. 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.
      Citations: 101     Fields:    Translation:HumansCells
    41. Kerr KM, Cahoon M, Bosco DA, Hedstrom L. Monovalent cation activation in Escherichia coli inosine 5'-monophosphate dehydrogenase. Arch Biochem Biophys. 2000 Mar 01; 375(1):131-7. PMID: 10683258.
      Citations: 7     Fields:    Translation:Cells
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