I have two major research directions. One, in cell biology, involves the routes and mechanisms of cholesterol trafficking inside cells. The second is the development of labs for use in secondary schools.
Cholesterol plays a critical role in the structure and function of mammalian cell membranes and is so important that cells obtain this lipid in two ways: by synthesis or by diet. Since organelle membranes contain different amounts of cholesterol, the delivery of this lipid to different membranes inside the cell is complex and must be tightly regulated. The exact routes and mechanisms of this intracellular cholesterol traffic are still unclear. Our research focuses on the role of membrane tubules in this process. When we inhibit the formation of membrane tubules, the steady state distribution of intracellular cholesterol is significantly altered. By immunofluorescence microscopy, cholesterol colocalizes with proteins that identify the recycling endosome. This free cholesterol enters from the plasma membrane and the distributions of several proteins involved in the regulation of this endocytic traffic are altered under these conditions, but distribution of proteins involved in coated, vesicular traffic are not affected. We also find that the distribution of a lipid that preferentially associates with cholesterol is also affected by the inhibition of membrane tubules. These data indicate a route that free cholesterol follows inside cells. Our current projects involve determining the exact entry mechanism by which this free cholesterol enters this route.
We have use this same approach to investigate two diseases which involve cholesterol. Niemann-Pick C is primarily a neurological disorder that results from a defect in cholesterol trafficking. Altered processing of amyloid precursor protein leads to Alzheimer's Disease, and cholesterol has been implicated in this process.
Currently, we have two lab activities undergoing development: a protein electrophoresis lab involving plants, signaling, and gene expression; a chromatography lab designed to investigate the changing colors of leaves in autumn.
H&S EGI Award
"A role for Rab11 in the processing of Amyloid Precursor Protein"