My name is Carolyn Barnes, and I am working at the SRF Research Center this summer! I recently graduated from the University of Tennessee, Knoxville with a B.S. in chemistry. At UTK, I worked in Dr. Michael Best’s lab. My project there involved optimizing a protocol to capture and isolate peripheral membrane binding proteins using liposomes containing special lipid probes.
This summer at the SRF Research Center, I am working on the atherosclerosis project with Dr. Matthew O’Connor. This project is employing a small molecule approach to find drug candidates that can solubilize toxic molecules found in atherosclerotic plaques. Atherosclerosis accounts for 44% of deaths worldwide and is caused by increased concentrations of cholesterol in the blood. Atherosclerosis is nearly ubiquitous in all humans as a result of aging. I am testing the ability of potential drug candidates to solubilize cholesterol and toxic cholesterol derivatives. Cholesterol can undergo chemical transformations in atherosclerotic plaques, becoming toxic oxidized derivatives that can cause cell death. One of the oxysterol derivatives is 7-ketocholesterol (7KC). We are working on finding a drug candidate that can selectively bind 7KC without binding to cholesterol, since cholesterol is important for the function of cells while 7KC has no beneficial biological roles.
Through the use of an automated solubilization assay, we are screening different drug derivatives against cholesterol and 7KC to search for one that shows very high affinity and specificity for 7KC over cholesterol. Additionally, we have been able to test several drug candidates against a number of compounds found in the body that resemble cholesterol. This allows us to screen for compounds that bind with our drug candidates that might require further testing to verify they don’t produce unwanted off-target effects.