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Research in the Sturley laboratory focuses on the regulation of sterol and fatty acid homeostasis in humans which, when aberrant, has profound consequences with regard to manifestation of several disease states including hyperlipidemia, obesity and neurodegenerative disorders such as Alzheimer's disease. The levels of these metabolites are under precise metabolic control because despite their essential nature, they are toxic in excess. A genetic approach has been applied in the Sturley lab using Saccharomyces cerevisiae (yeast) as a model organism. The genes encoding the catalytic steps in sterol and diacylglycerol esterification have been identified in yeast, and as a consequence their human counterparts have also been identified. Each of these processes; the production of steryl ester or triglyceride are significant independent components of diseases such as atherosclerosis and obesity. The processes of sterol and fatty acids movement within the cell are also under scrutiny by Dr. Sturley's group. Three transport processes have been characterized at the molecular level in yeast and mammalian cells. When defective, this leads in one case to the human syndrome, Niemann Pick type C, a lethal cholesterol storage lysosomal disorder, typified by neurodegeneration. Malathi, K., K. Higaki, A.H. Tinkelenberg, D.A. Balderes, D. Almanzar-Paramio, L.J. Wilcox, N. Erdeniz, F. Redican, M. Padamsee, Y. Liu, S. Khan, F. Alcantara, E.D. Carstea, J.A. Morris, S.L. Sturley. Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution. J Cell Biol 164:547-56, 2004. Wilcox L.J, Balderes D.A., Wharton B., Tinkelenberg A.H., Rao G., Sturley S.L. Transcriptional profiling identifies two members of the ATP-binding-cassette transporter superfamily required for sterol uptake in yeast. J Biol Chem 277:32466–32472, 2002. Liang J-S, Distler, O., Cooper, D., Jamil, H., Deckelbaum, R.J., Ginsberg, H., and Sturley, S.L. HIV protease inhibitor-induced hyperlipidemia: Increased secretion of apoprotein B - lipoproteins. Nature Medicine 7:1327-1331, 2002. |
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Stephen L. Sturley, Ph.D., Associate Professor of Clinical Nutrition