Jonathan D. Smith, PhD

We apply cell/molecular biology, biochemistry, and genetics/genomics to study three areas related to cardiovascular disease:

1. Atherosclerosis is the most common cause of cardiovascular disease and stroke. Atherosclerosis is initiated by high plasma cholesterol leading to monocyte entry into the artery wall and differentiation into macrophages, which take up lipoprotein cholesterol to become lipid engorged foam cells. We are identifying genes that alter atherosclerosis susceptibility in a mouse model and testing whether they play a role in coronary artery disease in humans.
2. The mechanism by which macrophages get rid of excess cholesterol is via a protective process known as reverse cholesterol transport. This involves moving cholesterol out of the cell via a membrane protein called ABCA1 and assembling this cholesterol onto apoAI to form HDL. We are studying how ABCA1 transfers lipids from the cell to apoAI. We are also studying how apoAI can become dysfunctional so that it can no longer participate in reverse cholesterol transport. We have created an apoAI variant that is resistant to becoming dysfunctional, which may be useful as a human therapeutic.
3. We are also examining the genetics and functional genomics of atrial fibrillation, a common arrhythmia that often leads to strokes. Together with Drs. Mina Chung, Dave Van Wagoner, and John Barnard, we have performed a genome wide association study for atrial fibrillation, and we are now working to determine how these common genetic variants act to alter susceptibility to this disease.