The focus of my research is the identification and characterization of genes and gene networks that influence cardiovascular disease risk. Research by multiple investigators indicates that entire transcriptional networks play roles in genetic responses to environmental challenges. My goal is to identify gene by environment responses to dietary fat and salt that predispose individuals to cardiovascular disease. Identifying and understanding the mechanisms by which these genetic networks are regulated will provide molecular therapeutic targets for prevention of atherosclerosis.
The majority of my studies are being conducted using the Southwest National Primate Research Center’s pedigreed, genotyped baboons. In previous work in conjunction with Dr. Michael Mahaney [CV] and Dr. Jeff Rogers [CV], my research group constructed a second-generation baboon genome linkage map. Using the baboon linkage map in conjunction with a novel expression array approach, we positionally cloned and characterized endothelial lipase, a gene that influences HDL-cholesterol. Furthermore, we identified molecular genetic mechanisms by which variation in endothelial lipase influences variation in HDL-cholesterol. We are conducting additional investigations to understand the dietary fat genetic network response that differs between low and high HDL-cholesterol baboons. We are also in the process of positionally cloning a gene and characterizing networks that influence variation in blood pressure and a gene and corresponding networks that influence variation in LDL-cholesterol. The genetic and physiologic similarity between baboons and humans allow us to directly translate these findings to human cardiovascular disease susceptibility using the San Antonio Family Heart Study genetic resource.
In addition to the cardiovascular disease studies on adult baboons we are studying programming by the fetal environment on postnatal offspring cardiovascular health. These studies, which focus on gene by environment interactions that alter the epigenome, use a nonhuman primate model of fetal development in concert with molecular genetic and genomic tools to determine the mechanisms by which the in utero environment influences offspring risk of cardiovascular disease. Because of the physiologic similarity between baboon and human pregnancy, the outcomes from these studies are directly applicable to human health.
