Dr. Srinivasa Reddy’s laboratory studies physiological and pathological phenomena mediated by arachidonic acid (AA) and its metabolites, which are implicated in a number of disease processes including acute and chronic inflammation, cardiovascular disease, immune response, arthritis, inflammatory bowel disease, respiratory disorders and cancer. Several projects are currently underway:

1. Oxidized phospholipids and gene expression: Reddy’s laboratory identified several genes, whose expression is regulated by the biologically active oxidized lipids (AA-derived/mediated) in human aortic endothelial cells. Reddy’s laboratory has shown that one of these genes, MAP-Kinase Phosphatase-1 (MKP-1), is required for oxidized-lipid-induced monocyte/endothelial interactions (a critical step in the development of cardiovascular diseases). One of the main interests in Reddy’s laboratory is to determine the mechanism(s) of action of MKP-1 in atherosclerosis.
2. HDL-associated enzymes and their cellular counterparts participate in the inactivation inflammatory responses initiated by oxidized phospholipids: HDL-associated enzymes possess anti-atherogenic properties that may be due, in part, to their interaction with oxidized LDL (source for oxidized phospholipids). One of these proteins, PON1, has been well-characterized for its anti-atherogenic properties; however, the mechanism of action of PON1 and its family members are unknown. Reddy’s laboratory has performed pioneering research in the cloning and characterization of PON2 and PON3 proteins. They have developed animal models to study the role of PON2 in atherosclerosis and to delineate the mechanism of action of PON proteins.
3. COX-2 (a second, inducible form of COX) plays an anti-atherogenic role in the development of atherosclerosis in mouse models: COX-2 is the target for a class of non-steroidal anti-inflammatory drugs (NSAID) termed COX-2 selective inhibitors. Clinical applications for COX-2 selective inhibitors include pain management (e.g., arthritis) and the prevention of certain types of colon cancer; however, the cardiovascular side effects of COX-2 selective inhibitors caused a withdrawal of these important pharmacological agents from the market. Reddy’s laboratory, in collaboration with Dr. Harvey Herschman, has established several conditional COX-2 knockout mice to unravel the role of COX-2 in vascular biology and inflammation.
4. ApoA-I mimetic peptides for the treatment of cardiovascular diseases: Over the last decade, Reddy’s laboratory, together with other researchers at UCLA and other institutions, have developed a class of anti-inflammatory agents based on Reddy’s work on oxidized lipids and HDL that show promise for the treatment of many inflammatory disorders including cancer.