Genetic insights into cardiovascular function and diseas

Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

Our laboratory is molecularly dissecting easily accessible cells important for atherosclerosis to gain new insights into the disease process. We are utilizing unbiased global genetic screens such as Serial Analysis of Gene Expression (SAGE) to study circulating human monocytes as they differentiate into plaque macrophages. Using this approach, we have identified the protooncogene FOS as a reactive disease marker expressed in monocytes and other transcriptional modulators in macrophages. In addition, we have observed networks of genes belonging to various functional pathways that are critical for inflammatory function. Studies are underway to determine the utility of the disease markers and the role of candidate genes in atherosclerosis. Another area of interest to our laboratory is the role of tumor suppressor gene p53 in cardiovascular function. We have previously shown that p53 can potently generate reactive oxidants in the mitochondria and that it is involved in chemotherapy induced heart failure. We are now investigating novel mechanisms of mitochondrial regulation by the nucleus that may be important for energy and oxidant generation. Ongoing studies indicate that these novel pathways may not only have direct consequences on cardiovascular function but that they may also be important in inflammatory function. Various molecular techniques such as mouse conditional and human somatic cell gene knockout models are being used to address these questions.