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The major focus of Dr. Deckelbaum's laboratory is to determine regulatory mechanisms for cell-lipid particle interaction, cell cholesterol and triglyceride metabolism, and lipid-related gene expression. Current projects are defining the effects of lipid particle properties on their metabolism in the whole animal and with cells via receptor mediated and receptor independent pathways. Dr. Deckelbaum's laboratory has demonstrated that substantial amounts of lipoproteins and lipid emulsions can enter cells by receptor independent pathways. Integrated with these studies are studies on how different lipids, especially free fatty acids and various sphingolipids modulate sterol regulatory element binding protein (SREBP) mediated gene expression, focusing on genes affecting cell and whole body triglycerides and cholesterol homeostasis. Major areas of interest include: a) the role of triglyceride fatty acyl composition on modulating interaction of model lipid triglyceride-rich particles with apoprotein E and subsequent effects on cell and tissue metabolism in vitro, and in vivo, in mouse models. Dr. Deckelbaum's group is demonstrating that triglyceride-rich particles enriched in long chain omega-3 triglycerides do not enter tissues via classic receptor-dependent pathways but rather via other mechanisms which might relate to binding to non-receptor domains on the cell surface, such as phagocytosis or pinocytosis, and b) the actions of free fatty acids as potent regulators of a number of critical steps in cell lipid metabolism, via inhibition of expression mediated by sterol regulatory elements (SRE) in the promoter regions of lipid metabolism genes. Dr. Deckelbaum also coordinates programs related to the effects of varying nutrient intakes on expression of cardiovascular risk factors in children of different genetic backgrounds in both national and international studies. Overall, an important objective of Dr. Deckelbaum's program is to develop investigators who can translate basic nutritional questions into basic lipid and cellular biology. Worgall TS, Johnson RA, Seo, T, Gierens H, Deckelbaum RJ: Polyunsaturated fatty acids mediated decreases in sterol regulatory element mediatede gene transcription are linked to cell sphingolipid metabolism. J Biol Chem 277:3878-3885, 2002. Johnson RA, Hamilton JA, Worgall TS, Deckelbaum RJ: Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities: novel 13C-NMR analyses of free cholesterol partitioning. Biochemistry 42:1637-1645, 2003. Darnton-Hill I, Margetts B, Deckelbaum, RJ. Public health nutrition and genetics: implications for nutrition policy and promotion. Proc Nutr Soc 63:173-85, 2004. |
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Richard J. Deckelbaum, M.D., (Chair) Robert R. Williams Professor of Nutrition, Professor of Pediatrics and Professor of Epidemiology; Director, Institute of Human Nutrition