PiN Faculty Member - Dennis Selkoe, MD

Dennis Selkoe, MD

Vincent and Stella Coates Professor of Neurologic Diseases

Harvard Institutes of Medicine
Ann Romney Center for Neurologic Diseases
Harvard Institutes of Medicine Room 730
4 Blackfan Street
Boston, MA 02115
Tel: 617-525-5200
Fax: 617-525-5252
Email: dselkoe@partners.org
Visit my lab page here.



Our laboratory is interested in the biochemistry and molecular and cell biology of neuronal degeneration during aging of the mammalian brain and particularly in Alzheimer’s (AD) and Parkinson’s (PD) diseases. The laboratory originally developed methods for the purification and analysis of the intraneuronal paired helical filaments and extracellular amyloid fibrils that are the hallmarks of the neuropathology of AD. Extensive studies of the trafficking and processing of the β-amyloid precursor protein (APP), a membrane glycoprotein critically involved in AD, have been undertaken and continue. The lab discovered that Aβ is normally produced from APP throughout life, enabling dynamic cell biological studies of the mechanism of Aβ production and its pharmacological inhibition. The function of APP and the toxic properties of various Aβ assemblies on cultured neurons and in relevant mouse models are being examined. We discovered that presenilin is the active site of γ-secretase and study its role in APP and Notch proteolysis. Finally, a similar approach is bring applied to the function and dysfunction of gene products implicated in PD, particularly α-synuclein. We recently discovered that α-synuclein exists normally as α-helically folded tetramers and that their destabilization may lead to PD. We use a wide range of methods, including cell culture, protein biochemistry, molecular biology, immunohistochemistry, confocal and electron microscopy, electrophysiology and mouse modeling.



Last Update: 3/25/2015



Publications

For a complete listing of publications click here.

 


 



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