Sidhartha Chafekar, Ph.D.
Postdoctoral research fellow

Education
Academic Medical Center, University of Amsterdam, The Netherlands, 2007

Lab
Martin Duennwald

Research Interests
Huntington’s disease (HD) is an autosomal-dominant, adult-onset neurodegenerative disorder characterized by chorea, psychiatric disturbances and dementia. HD is caused by a CAG repeat expansion in exon 1 of the Huntingtin (Htt) gene. The resulting protein, mutant Htt containing expanded polyglutamine (polyQ), forms nuclear aggregates in neurons in specific regions of the brain including the striatum and cortex, where severe neurodegeneration is observed. Huntington disease (HD) inclusions are stained with anti-ubiquitin and anti-proteasome antibodies. This, together with proteasome activity studies on transfected cell, suggested that alterations in the ubiquitin-proteasome system (UPS) might contribute to HD pathogenesis. It is also in the striatum and cortex that enhanced neuronal induction of the interferon-gamma -inducible immunoproteasome subunits was found in HD patients. My current project is to elucidate the role of the immunoproteasome on polyQ expanded mutant Htt and wildtype Htt expressing mouse striatal neurons, its effects on Htt fragmentation, aggregation and toxicity, and the molecular mechanisms underlying these effects.

Publications
Chafekar, S. M. (2008). Increased Aβ_1-42 production sensitizes neuroblastoma cells for ER stress toxicity. Curr Alzheimer Res, Accepted.

Chafekar, S. M., Baas, F. & Scheper, W. (2008). Oligomer-specific Abeta toxicity in cell models is mediated by selective uptake. Biochim Biophys Acta. [Epub ahead of print]
PMID: 18602001

Chafekar, S. M., Hoozemans, J. J., Zwart, R., Baas, F. & Scheper, W. (2007). Abeta _1-42 induces mild endoplasmic reticulum stress in an aggregation state-dependent manner. Antioxid Redox Signal 9, 2245-54.
PMID: 17979527

Chafekar, S. M., Malda, H., Merkx, M., Meijer, E. W., Viertl, D., Lashuel, H. A., Baas, F. & Scheper, W. (2007). Branched KLVFF tetramers strongly potentiate inhibition of beta-amyloid aggregation. Chembiochem 8, 1857-64.
PMID: 17763487

Hoozemans, J. J., Chafekar, S. M., Baas, F., Eikelenboom, P. & Scheper, W. (2006). Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease. Curr Med Chem 13, 2599-605.
PMID: 17017913

Contact Details:
email: chafekar@bbri.org, tel. 617-658-7719