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| Aging | Research | Sambamurti Lab |
Sambamurti Lab Kumar Sambamurti, Ph.D. Office: (843) 792 4346 Interests: My long-term goals are to understand the mechanisms of degeneration with respect to the triggering events, the cascade of events and protective mechanisms, using a combination of modern methods of genomics and proteomics to identify useful candidate genes and proteins and characterize them using classical methods such as mutagenesis, genetics, cell biology and protein chemistry. The body is constantly generating high levels of waste as a byproduct of normal metabolism and has evolved mechanisms to clear them. The major risk factor for several degenerative diseases is aging possibly due to reduced tolerance and failure of protective mechanisms. My current focus is to understand the regulation of processing in AD pathogenesis. Our recent findings show that GPI-anchored proteins influence Aß biogenesis. In addition, we have data suggesting that the secretases that cleave APP to Aß, at least partly distribute into a detergent resistant membrane compartment referred to as lipid rafts. This membrane microdomain is not well characterized and is a subject of intense research from the perspective of signal transduction. Recent reports suggest that the Aß generated in association with these rafts in the presence of high levels of cholesterol may be more pathogenic, as it is bound to gangliosides and has greater tendency to aggregate. Previous studies showing that apolipoprotein E variants can influence the onset and course of AD suggested that cholesterol plays in role in the pathogenesis of AD. This has renewed interest in looking at the effects of mutations in lipid trafficking and metabolism on the generation, turnover, aggregation and toxicity of Aß in AD. Thus studies in my laboratory will be focused on a deeper understanding of lipid raft structures and their changes induced by dietary fats and changes in lipid rafts structures. Professional History: Education: Ph.D. Thesis: Post doctoral fellowship: Faculty Appointments: Selected Publications: Sambamurti, K., Hardy, J., Refolo, L.M. and Lahiri, D.K. (2002) Targeting APP metabolism for the treatment of Alzheimer’s disease. Drug Dev. Res. 56:211-227. Lahiri, D. K., Kotwal, G.J., Farlow, M.R., Sima, A., Kupsky, W., Sarkar, F.H. and Sambamurti, K. 2002. The role of the carboxyl-terminal fragments of amyloid precursor protein in Alzheimer's disease Ann N Y Acad Sci. 973:334-9. Sambamurti, K., Greig, N.H., Lahiri, D.K. (2002) Advances in the Cellular and Molecular Biology of the Beta-amyloid protein in Alzheimer's disease. J. Neuromol. Med. 1, 1-31 Tun, H.+, Marlow, L., Pinnix, I., Kinsey, R. and Sambamurti, K. (2002) Lipid rafts play an important role in A? biogenesis by regulating the ?-secretase pathway. J. Mol Neurosci 19, 31-5 Pinnix, I., Council, J.E., Roseberry, B., Onstead, L., Mallender, W., Sucic, J. and Sambamurti, K. (2001) Convertases other than Furin cleave ?-Secretase to its Mature Form. FASEB J. 15, 1810-1812 Pinnix, I., Musunuru, U., Tun, H., Golde, T., Sridharan, A., Ziani-Cherif C. and Sambamurti, K. (2001) A novel gamma secretase assay based on detection of the putative C-terminal fragment-gamma of APP. J. Biol. Chem. 276, 481-487 |
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