Mel Feany

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease
    Li Chen
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Neurosci 8:657-63. 2005
  2. ncbi request reprint Modelling neurodegenerative diseases in Drosophila: a fruitful approach?
    Miratul M K Muqit
    Department of Pathology, Division of Neuropathy, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Rev Neurosci 3:237-43. 2002
  3. pmc The unfolded protein response protects from tau neurotoxicity in vivo
    Carin A Loewen
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:. 2010
  4. pmc Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
    Valerie Cullen
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Brain 2:5. 2009
  5. ncbi request reprint A Drosophila model of Parkinson's disease
    M B Feany
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 404:394-8. 2000
  6. ncbi request reprint Parkin: a multipurpose neuroprotective agent?
    Mel B Feany
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, Massachusetts 02115, USA
    Neuron 38:13-6. 2003
  7. pmc ASIP Outstanding Investigator Award Lecture. New approaches to the pathology and genetics of neurodegeneration
    Mel B Feany
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Pathol 176:2058-66. 2010
  8. pmc Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formation
    Li Chen
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:3257-65. 2009
  9. pmc Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's disease model
    Sheng Zhang
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Dis Model Mech 2:247-66. 2009
  10. ncbi request reprint Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease
    Clemens R Scherzer
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Cambridge, MA 02139, USA
    Hum Mol Genet 12:2457-66. 2003

Collaborators

Detail Information

Publications35

  1. ncbi request reprint Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease
    Li Chen
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Neurosci 8:657-63. 2005
    ..Because increased number of inclusion bodies correlates with reduced toxicity, inclusion bodies may protect neurons from alpha-synuclein toxicity...
  2. ncbi request reprint Modelling neurodegenerative diseases in Drosophila: a fruitful approach?
    Miratul M K Muqit
    Department of Pathology, Division of Neuropathy, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Rev Neurosci 3:237-43. 2002
    ..Using fruitfly genetics to define the molecular pathways that underlie the neurodegenerative process is likely to improve substantially our understanding of the pathogenesis of the human diseases, and to provide new therapeutic targets...
  3. pmc The unfolded protein response protects from tau neurotoxicity in vivo
    Carin A Loewen
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:. 2010
    ..We then use loss of function genetic reagents to support a role for the unfolded protein response in protecting from tau neurotoxicity. Our findings suggest that the unfolded protein response can ameliorate the toxicity of tau in vivo...
  4. pmc Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
    Valerie Cullen
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Brain 2:5. 2009
    ..To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD), on aSyn processing...
  5. ncbi request reprint A Drosophila model of Parkinson's disease
    M B Feany
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 404:394-8. 2000
    ..Our Drosophila model thus recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease...
  6. ncbi request reprint Parkin: a multipurpose neuroprotective agent?
    Mel B Feany
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, Massachusetts 02115, USA
    Neuron 38:13-6. 2003
    ..These findings suggest a central role for parkin in maintaining dopaminergic neuronal integrity and strengthen the link between AR-JP and the more common sporadic form of Parkinson's disease...
  7. pmc ASIP Outstanding Investigator Award Lecture. New approaches to the pathology and genetics of neurodegeneration
    Mel B Feany
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Pathol 176:2058-66. 2010
    ..Use of these tractable simple models may become even more important as large amounts of genetic data emerge from genome-wide association studies in Alzheimer disease, Parkinson disease, and other neurodegenerative disorders...
  8. pmc Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formation
    Li Chen
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:3257-65. 2009
    ....
  9. pmc Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's disease model
    Sheng Zhang
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Dis Model Mech 2:247-66. 2009
    ....
  10. ncbi request reprint Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease
    Clemens R Scherzer
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Cambridge, MA 02139, USA
    Hum Mol Genet 12:2457-66. 2003
    ....
  11. pmc Oxidative stress mediates tau-induced neurodegeneration in Drosophila
    Dora Dias-Santagata
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 117:236-45. 2007
    ..In summary, our study identifies oxidative stress as a causal factor in tau-induced neurodegeneration in Drosophila...
  12. ncbi request reprint Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo
    Tudor A Fulga
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Harvard New Research Building Room 652, 77 Louis Pasteur Avenue, Boston, MA 02115, USA
    Nat Cell Biol 9:139-48. 2007
    ..These findings raise the possibility that a direct interaction between tau and actin may be a critical mediator of tau-induced neurotoxicity in Alzheimer's disease and related disorders...
  13. ncbi request reprint S/P and T/P phosphorylation is critical for tau neurotoxicity in Drosophila
    Michelle L Steinhilb
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Neurosci Res 85:1271-8. 2007
    ..We provide direct evidence in an animal model system to support the role of phosphorylation at SP/TP sites in playing a critical role in tau neurotoxicity...
  14. pmc Tau phosphorylation sites work in concert to promote neurotoxicity in vivo
    Michelle L Steinhilb
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Mol Biol Cell 18:5060-8. 2007
    ..These findings suggest that serine-proline/threonine-proline sites cooperate to mediate neurodegeneration in vivo...
  15. pmc Connecting cell-cycle activation to neurodegeneration in Drosophila
    Vikram Khurana
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Harvard New Research Building Room 652, 77 Louis Pasteur Avenue, Boston, MA 02115, USA
    Biochim Biophys Acta 1772:446-56. 2007
    ..We suggest how powerful research tools in Drosophila might be utilized to approach fundamental questions that remain...
  16. ncbi request reprint Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo
    Magali Periquet
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 27:3338-46. 2007
    ....
  17. ncbi request reprint Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease
    Tiago Fleming Outeiro
    Alzheimer s Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA
    Science 317:516-9. 2007
    ..Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging...
  18. ncbi request reprint Comparison of pathways controlling toxicity in the eye and brain in Drosophila models of human neurodegenerative diseases
    Srimoyee Ghosh
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 77 Louis Pasteur Avenue, Room 630, Boston, MA 02115, USA
    Hum Mol Genet 13:2011-8. 2004
    ..These findings outline common pathways of neurotoxicity, demonstrate disease- and cell-type specific pathways and identify a common vitamin as a potential therapy in polyglutamine disorders...
  19. pmc Genetic modifiers of tauopathy in Drosophila
    Joshua M Shulman
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 165:1233-42. 2003
    ..Our results demonstrate that kinases and phosphatases control Tau-induced neurodegeneration and have important implications for the development of therapies in Alzheimer's disease and related disorders...
  20. pmc Lysosomal dysfunction promotes cleavage and neurotoxicity of tau in vivo
    Vikram Khurana
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Genet 6:e1001026. 2010
    ..Thus, caspase cleavage of tau may be a molecular mechanism through which lysosomal dysfunction and neurodegeneration are causally linked in Alzheimer's disease...
  21. doi request reprint Why size matters - balancing mitochondrial dynamics in Alzheimer's disease
    BRIAN DUBOFF
    Brigham and Women s Hospital and Harvard Medical School, Department of Pathology, Brigham and Women s Hospital, Harvard New Research Building, Room 630, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Trends Neurosci 36:325-35. 2013
    ..We highlight recent findings that TAU exerts a determinative effect in the regulation of mitochondrial dynamics, and therefore neuronal function. In this process, the GTPase DRP1 has emerged as a key target of both Aβ and TAU...
  22. ncbi request reprint Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity
    Eirene Kontopoulos
    Department of Pathology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Hum Mol Genet 15:3012-23. 2006
    ..These findings implicate nuclear alpha-synuclein in promoting nigrostriatal degeneration in Parkinson's disease and encourage exploration of histone deacetylase inhibitors as potential therapies for the disorder...
  23. ncbi request reprint From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease
    Joshua M Shulman
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Opin Neurol 16:443-9. 2003
    ..In this review, we emphasize the most recent accomplishments and chart the potential rewards in translating lessons from Drosophila models to clinical therapeutics...
  24. ncbi request reprint TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model
    Vikram Khurana
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Harvard New Research Building Room 652, 77 Louis Pasteur Avenue, Boston, Massachusetts 02115, USA
    Curr Biol 16:230-41. 2006
    ..However, the critical questions of whether cell-cycle activation is causal or epiphenomenal to tau-induced neurodegeneration and which signaling pathways mediate cell-cycle activation in tauopathy remain unresolved...
  25. ncbi request reprint Clinical correlates in an experimental model of repetitive mild brain injury
    Rebekah Mannix
    Division of Emergency Medicine, Boston Children s Hospital, Boston, MA Harvard Medical School, Boston, MA
    Ann Neurol 74:65-75. 2013
    ..Here, we use an experimental model of rmTBI to address these clinical controversies...
  26. doi request reprint In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons
    Tara L Spires-Jones
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 28:862-7. 2008
    ....
  27. ncbi request reprint Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses
    Liisa Myllykangas
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB Room 652, Boston, MA 02115, USA
    Neurobiol Dis 19:194-9. 2005
    ..Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs...
  28. ncbi request reprint Polyglutamines stop traffic: axonal transport as a common target in neurodegenerative diseases
    Mel B Feany
    Department of Pathology, Division of Neuropathology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Neuron 40:1-2. 2003
    ..Szebenyi and colleagues find that polyQ proteins directly inhibit fast axonal transport using axoplasm from the squid giant axon and suggest that axonal transport defects may be a common feature of polyQ disease pathogenesis...
  29. ncbi request reprint New genetic insights into Parkinson's disease
    Mel B Feany
    Department of Pathology, Division of Neuropathology, Brigham and Women s Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 351:1937-40. 2004
  30. ncbi request reprint Yeast genetics targets lipids in Parkinson's disease
    Clemens R Scherzer
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Trends Genet 20:273-7. 2004
  31. pmc Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants
    Jessica C Greene
    Department of Genome Sciences, University of Washington, P O Box 357730, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:4078-83. 2003
    ....
  32. pmc Calpain-cleavage of alpha-synuclein: connecting proteolytic processing to disease-linked aggregation
    Brian M Dufty
    Department of Biology, Boise State University, Boise, ID 83725, USA
    Am J Pathol 170:1725-38. 2007
    ..These findings suggest that calpain I may participate in the disease-linked aggregation of alpha-Syn in various alpha-synucleinopathies...
  33. ncbi request reprint Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neurons
    Nathan R Deleault
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Neurochem 85:1614-23. 2003
    ..Our work reveals the presence of mechanisms in neurons that specifically counterbalance the production of misfolded PrP conformations, and provides an opportunity to study these processes in a model organism amenable to genetic analysis...
  34. ncbi request reprint Senseless makes sense for spinocerebellar ataxia-1
    Vikram Khurana
    Nat Neurosci 8:1422-4. 2005
  35. ncbi request reprint Accelerated accumulation of misfolded prion protein and spongiform degeneration in a Drosophila model of Gerstmann-Sträussler-Scheinker syndrome
    Brendan A Gavin
    Department of Biology, Dartmouth College, Hanover, New Hampshire 03755, USA
    J Neurosci 26:12408-14. 2006
    ....

Research Grants20

  1. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2005
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  2. Mechanisms Underlying Neuronal Cell Type Specificity in Neurodegeneration
    Mel B Feany; Fiscal Year: 2010
    ..Our studies seek to determine the mechanisms that underlie specific loss of identified neurons as part of a longer term effort to devise effective treatments for these devastating disorders. ..
  3. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2001
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  4. Genetic Dissection of Neurodegenerative Dementias
    Mel Feany; Fiscal Year: 2005
    ..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..
  5. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2005
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  6. Drosophila model of amyotrophic lateral sclerosis
    Mel Feany; Fiscal Year: 2006
    ..The role of excitotoxicity will be explored with genetic manipulations, in particular by overexpression of glial glutamate transporters. ..
  7. Drosophila model of amyotrophic lateral sclerosis
    Mel Feany; Fiscal Year: 2007
    ..The role of excitotoxicity will be explored with genetic manipulations, in particular by overexpression of glial glutamate transporters. ..
  8. Aging in Drosophila models of human neurodegeneration
    Mel Feany; Fiscal Year: 2007
    ..Pathways critical for these vulnerabilities will provide important therapeutic targets. ..
  9. Mechanisms Underlying Neuronal Cell Type Specificity in Neurodegeneration
    Mel Feany; Fiscal Year: 2009
    ..Our studies seek to determine the mechanisms that underlie specific loss of identified neurons as part of a longer term effort to devise effective treatments for these devastating disorders. ..
  10. Drosophila model of amyotrophic lateral sclerosis
    Mel Feany; Fiscal Year: 2005
    ..The role of excitotoxicity will be explored with genetic manipulations, in particular by overexpression of glial glutamate transporters. ..
  11. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2004
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  12. Genetic Dissection of Neurodegenerative Dementias
    Mel Feany; Fiscal Year: 2001
    ..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..
  13. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2002
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  14. Genetic Dissection of Neurodegenerative Dementias
    Mel Feany; Fiscal Year: 2002
    ..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..
  15. GENETIC MODEL OF NEURODEGENERATION
    Mel Feany; Fiscal Year: 2003
    ..A co-sponsor expert in human molecular genetics and neurodegenerative diseases has been selected to complement the primary laboratory's expertise in Drosophila molecular genetics and development. ..
  16. Genetic Dissection of Neurodegenerative Dementias
    Mel Feany; Fiscal Year: 2003
    ..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..
  17. Drosophila Model of Parkinson's Disease
    Mel Feany; Fiscal Year: 2003
    ..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
  18. Drosophila model of amyotrophic lateral sclerosis
    Mel Feany; Fiscal Year: 2004
    ..The role of excitotoxicity will be explored with genetic manipulations, in particular by overexpression of glial glutamate transporters. ..
  19. Genetic Dissection of Neurodegenerative Dementias
    Mel Feany; Fiscal Year: 2004
    ..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..