Lipid transport, apoptosis, cancer
Despite being vilified in the popular press due to its connections to heart disease, cholesterol is an essential component of cell membranes and the precursor for hormones, bile acids and vitamins. Cholesterol is obtained from the diet or is synthesized in all cells of the body. Because cholesterol is insoluble in water, it must be transported from sites of synthesis and adsorption to the cells where it will be utilized. Cholesterol is transported in lipoproteins in the blood stream and by either transport vesicles or binding proteins within the cell. The focus of my studies is intracellular cholesterol transport. In cells, cholesterol can be transported by two mechanisms; in vesicles that are exchanged between membranes by a slow, energy-dependent process, or by binding proteins that facilitate rapid, energy independent transport. Transport proteins extract a single molecule of cholesterol into a pocket that shields it from the aqueous environment during transit to an acceptor membrane where the cholesterol is deposited. Of interest to our lab is the oxysterol-binding protein (OSBP) and 11 OSBP-related protein family members (ORPs). In addition to cholesterol, ORPs bind cholesterol-like molecules called oxysterols, as well as other membrane lipids. While all members of this family share common binding partners and have a similar organization, they have a wide range of functions related to maturation of fat cells, cholesterol storage, cell division, fertility and neurological activity. My research project is focused on ORP4 and its unique role in regulating the survival and proliferation of cancer cells. Our research group has found that reducing ORP4 expression in immortalized and cancer cells causes growth arrest or death. This suggested that ORP4 is involved in a specific transport or signalling pathway that is required for cell survival. My doctoral project is to learn more about the function of ORP4 in both normal and malignant cells and determine whether ORP4 contributes to the enhanced survival and proliferation of cancer cells. I'll be doing this by exploring ORP4 lipid-binding and transfer, its interactions with other proteins and the effect of post-translational modifications on both of these properties.
Bachelor of Science (2008-2012)
Ryerson University, Department of Biology and Chemistry
Doctor of Philosophy (In Progress)
Dalhousie University, Department of Biochemistry and Molecular Biology
- Charman, M., Colbourne, T.R., Pietrangelo, A., Kreplak, L., Ridgway, N.D., (2014) Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival J.Biol.Chem 289:15705-15804 [PubMed]