Research Interests

Research interests include genetic and environmental causes of heart disease; human genetics, molecular biology, induced mutant animal models; and human nutrition and metabolism. As a physician/scientist, I have studied the complex environmental and genetic determinants of heart disease susceptibility. Most of my work has been devoted to understanding the genetic basis of the abnormal lipoprotein phenotypes associated with coronary heart disease susceptibility. My laboratory was the first to isolate the apolipoprotein genes, which code for proteins that coat lipoprotein particles. The apolipoproteins regulate lipoprotein synthesis and serve as cofactors for lipoprotein processing reactions and ligands for lipoprotein receptors. Our studies of apolipoprotein gene expression provided new insights into the regulation of lipoprotein levels. We also showed that common genetic variation in these genes influence lipoprotein levels, atherosclerosis susceptibility, and even survival in the general population. Most recently we used these genes to make transgenic and knockout mouse models of lipoprotein disorders. This work resulted in the creation of the first mouse model that develops human-like atherosclerotic lesions. This model is now being used to study lesion pathogenesis, identify genes that suppress or enhance the phenotype, and develop novel therapies.

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Section 42: Medical Physiology and Metabolism