Dept. of Nutritional Sciences
School of Env & Biol Sciences
65 Dudley Road
New Brunswick, NJ 08901-0231
Cellular lipid transport, structure and function of lipid transport proteins, intestinal lipid transport and systemic energy metabolism
1) What are the functions of cytoplasmic fatty acid-binding proteins (FABP) in intracellular lipid transport and metabolism? Why do different cell types have different FABP? What are the protein structural determinants of functional differences between members of the FABP gene family?
2) Fatty acids (FA) and monoacylglycerols (MG) delivered to the intestinal cell via the diet or via the bloodstream are metabolized differently--how is this 'metabolic polarity' established and maintained? How does intestinal transport and metabolism of FA's and MG's impact whole body energy homeostasis?
3) How does the intracellular cholesterol-binding protein, Niemann-Pick type C2 protein (NPC2), function in the transport of cholesterol out of endosomes and lysosomes, and how do NPC2 and NPC1 proteins function together?The laboratory us a combination of biochemical, biophysical, cell and molecular biological, and whole animal studies to answer these questions. For example, the structural determinants of the lipid transport properties of FABP and NPC2 proteins are probed using site-directed mutagenesis, fluorescence spectroscopy, and membrane biophysics approaches. Cell culture systems such as the Caco-2 human intestinal cell line are used to examine cellular lipid transport using biochemical methods and confocal microscopy. The functions of FABPs are also studied using transgenic mouse models in which specific FABP expression has been "knocked out". Cells from patients with NPC disease are used to examine the function of the NPC2 protein in cholesterol trafficking. These studies are providing fundamental information about the cellular trafficking of lipids, with the ultimate goal of enabling effective preventive and therapeutic approaches to a variety of pathologic conditions including obesity, cardiovascular disease, and lipid-storage diseases.