Assistant Professor of Medicine; Director of Environmental Cardiology
David Geffen School of Medicine
Los Angeles, CA 90095-1679
Campus Mailcode: 167917
The main research interests of our laboratory are focused on two areas of investigation:
Environmental Cardiology: We are dissecting the mechanisms by which exposure to air particulate matter promotes atherosclerosis and ischemic heart disease and studying gene-environment interactions of relevance in the development of cardiovascular disease. In recent years, we have found that air pollutant chemicals such as those present in diesel exhaust particles are able to synergize with oxidized phospholipids generated within oxidized LDL, in the promotion of proatherogenic genes in vascular endothelial cells. We have also determined that inhalation of ambient ultrafine particles lead to systemic prooxidant and proinflammatory effects that result in the development of dysfunctional HDL and enhancement of atherosclerotic lesions.
Biology of vascular oxidative stress: We are interested in genes and pathways of relevance in the oxidative stress generated in vascular inflammatory entities such as atherosclerosis and ischemia reperfusion. We have determined that heme oxygenase-1 (HO-1) is an important antioxidant and anti-inflammatory protective gene and together with its transcriptional regulator Nrf2, they may play a central role in orchestrating the antioxidant defense of vascular cells. However, while HO-1 is an anti-atherogenic gene, Nrf2 promotes atherosclerosis instead partly due to the regulation of genes involved in lipid metabolism and cholesterol transport. This underscores t]he complexity of reactive oxygen species (ROS) signaling in vascular cells. We are currently studying how HO-1 expression modulates various inflammatory pathways via the use of genetic and biochemical approaches.