Mel Feany, M.D., Ph.D.

 

Professor of Pathology

Brigham and Women's Hospital
Department of Pathology
New Research Building, Room 630
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-525-4405
Fax: 617-525-4422
Email: mel_feany@hms.harvard.edu
Visit my lab page here.




The molecular mechanisms underlying neurodegeneration in human disorders like Alzheimer’s disease and Parkinson’s disease remain largely mysterious, in part because genetic analysis in patients and vertebrate models is laborious. Disease models in simpler organisms, like Drosophila, harness the power of genetics to define cellular pathways underlying the specific destruction of postmitotic neurons in neurodegenerative disorders. In our laboratory we have created fruit fly models of several human diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gerhig’s disease), and spinocerebellar ataxia type 1 (a disease produced by expanded polyglutamine repeats). Mutations in the a-synuclein gene cause familial Parkinson’s disease, and a-synuclein protein accumulates in intraneuronal inclusion bodies in both familial and nonfamilial Parkinson’s disease. By expressing normal and mutant human a-synuclein in flies, we have recreated key features of the human disorder: dopaminergic neurodegeneration, intracytoplasmic neuronal inclusion bodies containing a-synuclein, and progressive locomotor dysfunction. We have taken similar approaches to modeling Alzheimer’s disease, amyotrophic lateral sclerosis, and polyglutamine disorders in Drosophila. Genetic screens have been performed in these models to define the cellular pathways mediating neurodegeneration. Our results so far support a critical role for posttranslational modifications such as phosphorylation in modulating protein aggregation and neurotoxicity in our models. Candidate mediators defined in the Drosophila models are being investigated in mammalian systems, including human disease, to evaluate the role of the proteins in the pathogenesis of human neurodegenerative disorders.


For a complete listing of publications click here.



Last Update: 11/7/2013