Research Topics
| Mel FeanySummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson diseaseLi 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...- 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... 
Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivoValerie 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...- A Drosophila model of Parkinson's diseaseM 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... - ASIP Outstanding Investigator Award Lecture. New approaches to the pathology and genetics of neurodegenerationMel 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... - 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... - Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formationLi Chen
Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 119:3257-65. 2009.... - Oxidative stress mediates tau-induced neurodegeneration in DrosophilaDora 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... - Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivoTudor 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... - S/P and T/P phosphorylation is critical for tau neurotoxicity in DrosophilaMichelle 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... - Tau phosphorylation sites work in concert to promote neurotoxicity in vivoMichelle 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... - Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's diseaseClemens 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.... - Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's disease modelSheng Zhang
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Dis Model Mech 2:247-66. 2009.... - Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's diseaseTiago 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... - Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivoMagali Periquet
Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 27:3338-46. 2007.... - Connecting cell-cycle activation to neurodegeneration in DrosophilaVikram 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... - Lysosomal dysfunction promotes cleavage and neurotoxicity of tau in vivoVikram 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... - Comparison of pathways controlling toxicity in the eye and brain in Drosophila models of human neurodegenerative diseasesSrimoyee 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... - Genetic modifiers of tauopathy in DrosophilaJoshua 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... - Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicityEirene 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... - TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy modelVikram 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... - From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative diseaseJoshua 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..With the advent of neurodegenerative disease models, the fruit fly is rapidly assuming a unique niche in bench to bedside research... - Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinosesLiisa 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... - Polyglutamines stop traffic: axonal transport as a common target in neurodegenerative diseasesMel 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... 
In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neuronsTara L Spires-Jones
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Neurosci 28:862-7. 2008....- Yeast genetics targets lipids in Parkinson's diseaseClemens R Scherzer
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Trends Genet 20:273-7. 2004 - New genetic insights into Parkinson's diseaseMel 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 - Calpain-cleavage of alpha-synuclein: connecting proteolytic processing to disease-linked aggregationBrian 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... - Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutantsJessica 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.... - Senseless makes sense for spinocerebellar ataxia-1Vikram Khurana
Nat Neurosci 8:1422-4. 2005 - Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neuronsNathan 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... - Accelerated accumulation of misfolded prion protein and spongiform degeneration in a Drosophila model of Gerstmann-Sträussler-Scheinker syndromeBrendan A Gavin
Department of Biology, Dartmouth College, Hanover, New Hampshire 03755, USA
J Neurosci 26:12408-14. 2006....
Research Grants
- Drosophila Model of Parkinson's DiseaseMel Feany; Fiscal Year: 2005..We can abolish inclusion formation in a-synuclein transgenic flies, and will determine if inclusions are required for neurotoxicity. ..
- Mechanisms Underlying Neuronal Cell Type Specificity in NeurodegenerationMel 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. ..
- Genetic Dissection of Neurodegenerative DementiasMel Feany; Fiscal Year: 2005..These novel modifiers will represent candidate members of the presenilin complex, as well as upstream regulatory factors. ..
- Drosophila model of amyotrophic lateral sclerosisMel Feany; Fiscal Year: 2007..The role of excitotoxicity will be explored with genetic manipulations, in particular by overexpression of glial glutamate transporters. ..
- Aging in Drosophila models of human neurodegenerationMel Feany; Fiscal Year: 2007..Pathways critical for these vulnerabilities will provide important therapeutic targets. ..
- GENETIC MODEL OF NEURODEGENERATIONMel 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. ..