Nancy Bonini

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Silencing polyglutamine degeneration with RNAi
    Nancy M Bonini
    Department of Biology and University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Neuron 48:715-8. 2005
  2. pmc Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila
    Julide Bilen
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Genet 3:1950-64. 2007
  3. pmc Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3
    Joonil Jung
    Department of Biology and University of Pennsylvania, Philadelphila, PA 19104 6018, USA
    Hum Mol Genet 18:4843-52. 2009
  4. pmc A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1
    Melanie R Watson
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:24972-81. 2008
  5. pmc Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model
    Mimi Cushman-Nick
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Neuroscience Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Genet 9:e1003781. 2013
  6. pmc Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy
    Zhenming Yu
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Genet 7:e1001340. 2011
  7. pmc The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila
    Nan Liu
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nature 482:519-23. 2012
  8. pmc Protein interacting with C kinase (PICK1) is a suppressor of spinocerebellar ataxia 3-associated neurodegeneration in Drosophila
    Leeanne McGurk
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Mol Genet 21:76-84. 2012
  9. pmc Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila
    Shin Yi Shieh
    Department of Biology, University of Pennsylvania, PA 19104 6018, USA
    Hum Mol Genet 20:4810-21. 2011
  10. ncbi request reprint The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates
    N M Bonini
    Department of Biology, University of Pennsylvania, Philadelphia 19104 6018, USA
    Development 124:4819-26. 1997

Collaborators

Detail Information

Publications43

  1. ncbi request reprint Silencing polyglutamine degeneration with RNAi
    Nancy M Bonini
    Department of Biology and University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Neuron 48:715-8. 2005
    ..Such studies opened the door to a powerful new therapeutic approach now being pioneered: silencing of the dominant disease allele by RNA-mediated interference (RNAi), for the arrest--and potential reversal--of the disease process...
  2. pmc Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila
    Julide Bilen
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Genet 3:1950-64. 2007
    ..These findings provide new insight into molecular pathways of polyQ toxicity, defining novel targets for promoting neuronal survival in human neurodegenerative disease...
  3. pmc Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3
    Joonil Jung
    Department of Biology and University of Pennsylvania, Philadelphila, PA 19104 6018, USA
    Hum Mol Genet 18:4843-52. 2009
    ..This genetic in vivo confirmation of the pathological role of Ataxin-3 cleavage indicates that therapies targeting Ataxin-3 cleavage might slow disease progression in SCA3 patients...
  4. pmc A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1
    Melanie R Watson
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:24972-81. 2008
    ..These studies uncover cell-autonomous injury by SOD1 to motor neurons in vivo, as well as non-autonomous effects on glia, and provide the foundation for new insight into injury and protection of motor neurons in ALS...
  5. pmc Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model
    Mimi Cushman-Nick
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Neuroscience Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS Genet 9:e1003781. 2013
    ..Thus, we establish the first disaggregase or chaperone treatment administered after the onset of pathogenic protein-induced degeneration that mitigates disease progression. ..
  6. pmc Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy
    Zhenming Yu
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    PLoS Genet 7:e1001340. 2011
    ..These findings indicate that the generation of triplet repeat-derived siRNAs may dramatically enhance toxicity in human repeat expansion diseases in which anti-sense transcription occurs...
  7. pmc The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila
    Nan Liu
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nature 482:519-23. 2012
    ....
  8. pmc Protein interacting with C kinase (PICK1) is a suppressor of spinocerebellar ataxia 3-associated neurodegeneration in Drosophila
    Leeanne McGurk
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Mol Genet 21:76-84. 2012
    ..These findings indicate that interaction proteins may define a rich source of modifier pathways to target in disease situations...
  9. pmc Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila
    Shin Yi Shieh
    Department of Biology, University of Pennsylvania, PA 19104 6018, USA
    Hum Mol Genet 20:4810-21. 2011
    ..These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease...
  10. ncbi request reprint The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates
    N M Bonini
    Department of Biology, University of Pennsylvania, Philadelphia 19104 6018, USA
    Development 124:4819-26. 1997
    ....
  11. pmc Model organisms reveal insight into human neurodegenerative disease: ataxin-2 intermediate-length polyglutamine expansions are a risk factor for ALS
    Nancy M Bonini
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Mol Neurosci 45:676-83. 2011
    ..These studies provide an example of how model systems, when extended to human cells and human patient tissue, can reveal new mechanistic insight into disease...
  12. ncbi request reprint Human neurodegenerative disease modeling using Drosophila
    Nancy M Bonini
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, 415 S University Avenue, Philadelphia, PA 19104 6018, USA
    Annu Rev Neurosci 26:627-56. 2003
    ..The findings highlight Drosophila as an important model system in which to study the fundamental pathways influenced by these genes and have led to new insights into aspects of pathogenesis and modifier mechanisms...
  13. pmc Chaperoning brain degeneration
    Nancy M Bonini
    Department of Biology, University of Pennsylvania, Howard Hughes Medical Institute, Philadelphia 19104 6018, USA
    Proc Natl Acad Sci U S A 99:16407-11. 2002
    ..Hsp70 is a potent suppressor of both polyglutamine disease and Parkinson's disease in Drosophila. These studies provide the promise of treatments for human neurodegeneration through the up-regulation of stress and chaperone pathways...
  14. ncbi request reprint Surviving Drosophila eye development: integrating cell death with differentiation during formation of a neural structure
    N M Bonini
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Bioessays 21:991-1003. 1999
    ..Finally, we address how the Drosophila eye may allow identification of additional mechanisms that contribute to the normal integration of cell survival with appropriate events of cellular differentiation...
  15. ncbi request reprint Multiple roles of the eyes absent gene in Drosophila
    N M Bonini
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6018, USA
    Dev Biol 196:42-57. 1998
    ..Despite multiple roles at multiple stages of development of the fly, both the type I and type II forms of the protein, when expressed ectopically during larval development, can direct eye formation...
  16. ncbi request reprint CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease
    Joonil Jung
    Department of Biology, University of Pennsylvania, Philadelphila, PA 19104, USA
    Science 315:1857-9. 2007
    ..Pharmacological treatment to normalize acetylation suppressed instability. Thus, toxic consequences of pathogenic polyQ protein may include enhancing repeat instability...
  17. pmc Transcription factor YY1 functions as a PcG protein in vivo
    Lakshmi Atchison
    Department of Biology, Chestnut Hill College, 9601 Germantown Avenue, Philadelphia, PA 19118, USA
    EMBO J 22:1347-58. 2003
    ..Finally, we found that YY1, as well as Polycomb, required the co-repressor protein CtBP for repression in vivo. These results provide a mechanism for recruitment of vertebrate PcG complexes to DNA and demonstrate new functions for YY1...
  18. ncbi request reprint MicroRNA pathways modulate polyglutamine-induced neurodegeneration
    Julide Bilen
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 24:157-63. 2006
    ..These findings indicate that miRNA pathways dramatically modulate polyQ- and tau-induced neurodegeneration, providing the foundation for new insight into therapeutics...
  19. ncbi request reprint Biochemical and pathological characterization of Lrrk2
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Ann Neurol 59:315-22. 2006
    ..The studies herein explore the biological and pathological properties of Lrrk2...
  20. ncbi request reprint Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease
    Marc Meulener
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Curr Biol 15:1572-7. 2005
    ..Study of these flies will provide insight into the critical interplay of genetics and environment in PD...
  21. pmc Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS
    Andrew C Elden
    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nature 466:1069-75. 2010
    ..Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies...
  22. ncbi request reprint Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila
    Pavan K Auluck
    Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:2873-8. 2005
    ..These studies indicate that compounds that modulate the stress response are a promising approach to treat Parkinson's disease...
  23. ncbi request reprint Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease
    Pavan K Auluck
    Department of Neuroscience, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 295:865-8. 2002
    ..Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression...
  24. pmc RNA toxicity is a component of ataxin-3 degeneration in Drosophila
    Ling Bo Li
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6018, USA
    Nature 453:1107-11. 2008
    ..These studies reveal a role for the RNA in polyQ toxicity, highlighting common components in RNA-based and polyQ-protein-based trinucleotide repeat expansion diseases...
  25. pmc Polyglutamine genes interact to modulate the severity and progression of neurodegeneration in Drosophila
    Derek Lessing
    Department of Biology, University of Pennsylvania, Howard Hughes Medical Institute, Philadelphia, Pennsylvania, United States of America
    PLoS Biol 6:e29. 2008
    ..We propose that functional links between these genes are critical to disease severity and progression, such that therapeutics for one disease may be applicable to others...
  26. ncbi request reprint A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins
    Julide Bilen
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cell Cycle 5:2835-8. 2006
    ..These studies provide the foundation to define the miRNAs involved in neurodegenerative disease, and the biological pathways affected...
  27. ncbi request reprint Hosting neurotoxicity in polyglutamine disease
    Nan Liu
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell 127:1299-300. 2006
    ..Instead, they suggest that toxicity is solely due to interactions of Ataxin-1 with its normal binding partners...
  28. pmc Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging
    Marc C Meulener
    Department of Biology, University of Pennsylvania, and Howard Hughes Medical Institute, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:12517-22. 2006
    ..Overoxidation of DJ-1 with age and exposure to oxidative toxins may lead to inactivation of DJ-1 function, suggesting a role in susceptibility to sporadic Parkinson's disease...
  29. ncbi request reprint Drosophila as a model for human neurodegenerative disease
    Julide Bilen
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Annu Rev Genet 39:153-71. 2005
    ..This review focuses on fruit fly models of human neurodegenerative diseases, with emphasis on how fly models have provided new insights into various aspects of human diseases...
  30. ncbi request reprint Drosophila models of polyglutamine diseases
    H Y Edwin Chan
    Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
    Methods Mol Biol 217:241-51. 2003
  31. pmc DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function
    Ling Yang Hao
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 107:9747-52. 2010
    ..These findings link DJ-1, pink1, and parkin to mitochondrial integrity and provide the foundation for therapeutics that link bioenergetics and parkinsonism...
  32. ncbi request reprint Genetic modulation of polyglutamine toxicity by protein conjugation pathways in Drosophila
    H Y Edwin Chan
    Howard Hughes Medical Institute, Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Mol Genet 11:2895-904. 2002
    ..These data suggest that post-translational protein modification, including the ubiquitin/proteasome and the SUMO-1 pathways, modulate poly(Q) pathogenesis...
  33. ncbi request reprint Snaring the function of alpha-synuclein
    Nancy M Bonini
    Department of Biology and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cell 123:359-61. 2005
    ..These proteins are crucial for release of neurotransmitters at the neuronal synapse, vesicle recycling, and synaptic integrity...
  34. ncbi request reprint Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism
    John M Warrick
    Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 18:37-48. 2005
    ..Our results highlight the critical importance of host protein function in SCA3 disease and a potential therapeutic role of ataxin-3 activity for polyglutamine disorders...
  35. pmc Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathies
    Kunihiro Uryu
    The Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104 4283, USA
    Am J Pathol 168:947-61. 2006
    ..These data implicate predominantly Hsp90 in the formation of alpha-syn inclusions in PD and related alpha-synucleinopathies...
  36. ncbi request reprint Suppression of polyglutamine toxicity by the yeast Sup35 prion domain in Drosophila
    Ling Bo Li
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104 6018, USA
    J Biol Chem 282:37694-701. 2007
    ..These results suggest a trans effect of prion domains on pathogenic poly(Q) disease proteins in a multicellular environment and raise the possibility that Drosophila may allow studies of prion mechanisms...
  37. pmc Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants
    Derek Lessing
    Howard Hughes Medical Institute, University of Pennsylvania, 306 Leidy Laboratories, 433 South University Avenue, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 10:359-70. 2009
    ....
  38. ncbi request reprint Pharmacological prevention of Parkinson disease in Drosophila
    Pavan K Auluck
    Nat Med 8:1185-6. 2002
  39. ncbi request reprint Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila
    Shermali Gunawardena
    Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Neuron 40:25-40. 2003
    ..Thus, disruption of axonal transport by pathogenic polyQ proteins could contribute to early neuropathology in Huntington's and other polyQ expansion diseases...
  40. ncbi request reprint DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synuclein
    Marc C Meulener
    Department of Biology and Laboratory of Medicine of University of Pennsylvania, Philadelphia 19104 6084, USA
    J Neurochem 93:1524-32. 2005
    ..Furthermore, our results provide further evidence for the interplay between neurodegenerative disease-associated proteins...
  41. pmc Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models
    Antony A Cooper
    School of Biological Sciences, University of Missouri Kansas City, Kansas City, MO 64110, USA
    Science 313:324-8. 2006
    ..Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable...
  42. pmc An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis
    Annett Boeddrich
    Department of Neuroproteomics, Max Delbrueck Center for Molecular Medicine MDC, Berlin, Germany
    EMBO J 25:1547-58. 2006
    ..Together, these results define the VCP-Atx-3 association as a potential target for therapeutic intervention and suggest that it might influence the progression of spinocerebellar ataxia type 3...
  43. pmc RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
    Marcel P van der Brug
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Proc Natl Acad Sci U S A 105:10244-9. 2008
    ..These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner...

Research Grants9

  1. ACTIVITY OF THE ALZHEIMERS DISEASE PRESENIL IN PROTEIN
    Nancy Bonini; Fiscal Year: 2003
    ..The studies proposed here will clarify the biochemical activity of Presenilin in the processing of Notch, APP and other proteins, and may ultimately increase our understanding of the molecular causes of Alzheimer's disease. ..
  2. Molecular Genetic Analysis of Neurodegeneration
    Nancy Bonini; Fiscal Year: 2003
    ....
  3. Molecular Genetic Analysis of Neurodegeneration
    Nancy Bonini; Fiscal Year: 2004
    ....
  4. ACTIVITY OF THE ALZHEIMERS DISEASE PRESENIL IN PROTEIN
    Nancy Bonini; Fiscal Year: 2004
    ..The studies proposed here will clarify the biochemical activity of Presenilin in the processing of Notch, APP and other proteins, and may ultimately increase our understanding of the molecular causes of Alzheimer's disease. ..
  5. Molecular Genetic Analysis of Neurodegeneration
    Nancy Bonini; Fiscal Year: 2005
    ....
  6. Molecular Genetic Analysis of Neurodegeneration
    Nancy Bonini; Fiscal Year: 2006
    ....
  7. Molecular Genetic Analysis of Neurodegeneration
    Nancy Bonini; Fiscal Year: 2007
    ....
  8. Novel approaches to neural regeneration: Defining new genes & pathways
    Nancy Bonini; Fiscal Year: 2009
    ..abstract_text> ..
  9. Novel approaches to neural regeneration: Defining new genes & pathways
    Nancy M Bonini; Fiscal Year: 2010
    ..abstract_text> ..