My name is Elena Fulton, and I am a recent graduate from the University of Puget Sound, where I earned a B.S in Molecular Biology. Throughout college, I participate in directed research with Bryan Thines and worked to characterize the role of novel F-box proteins in plant stress response pathways. I also participated in a summer Research Experience for Undergraduates at the Gates Center for Regenerative Medicine in Denver, Colorado where I worked on a project geared towards designing full-thickness skin grafts using induced pluripotent stem cells. As a Summer Scholar, I have had the opportunity to work at the SRF Research Center with Dr. Matthew O’Connor. The O’Connor lab focuses on taking a small molecule approach to the treatment of atherosclerosis; this currently involves determining the efficacy of cyclodextrin molecules to induce efflux of a toxic sterol from atherosclerotic plaques therefor reducing the formation of these lesions.
Atherosclerosis is a leading cause of death worldwide and is characterized by the buildup of sterol-rich plaques in the arteries. My project seeks to test how well a class of molecules known as cyclodextrins (circular molecules made of glucose subunits) can remove the second most abundant sterol in an atherosclerotic plaque: 7-ketocholesterol (7KC). 7KC is a toxic molecule that greatly contributes to atherosclerosis by accelerating the formation of plaques, so removing it should reduce plaque size and reduce the likelihood of plaque rupture. To test the effectiveness of our cyclodextrin compounds, a small amount of human blood or a small piece of aortic pig tissue can be treated with a cyclodextrin solution. The amount of 7KC removed from the cells in both tissue types during incubation can then be measured to assess how well different cyclodextrin molecules work relative to each other.
These measurements give us an indirect measure of the effectiveness of each cyclodextrin compound, but to determine how successful our drug can remove 7KC from cells we need to know how much 7KC was in each tissue type to begin with. To determine the starting amount of 7KC, I am performing a total lipid extraction from untreated pig tissue and red blood cells and then measuring the concentration of 7KC in the extract. These values can then be compared to samples that were treated with cyclodextrin compounds to determine the effectiveness of each compound more precisely. This experiment will allow us to identify lead drug candidates which can be further assessed for clinical application.