Dr. Joseph L. Witztum, MD, Distinguished Professor of Medicine, University of California, San Diego
Discovery of the Central Role of Oxidized Phospholipids in Inflammation
Abstract: Many investigators had identified oxidized phospholipids (OxPL) as inflammatory agents in vitro but as these are largely products of non-enzymatic lipid peroxidation, there were no reagents to neutralize them and determine their importance in vivo. During studies to identify a specific antibody to identify oxidized LDL, we discovered an innate natural antibody, E06, and discovered it specifically bound to OxPL and neutralized them. E06 does not bind to unoxidized PL. We then showed that OxPL is an important DAMP, to which multiple components of innate immunity, including E06, scavenger receptor CD36 and CRP target. To determine if targeting OxPL is beneficial, we generated a transgenic mouse that secretes the E06 antibody and demonstrated in multiple disease models, including atherosclerosis and MASH among others, that neutralizing OxPL substantially reduces inflammation and disease. These studies demonstrate the centralized importance of OxPL in mediating and promoting inflammation in a wide variety of disease settings.
Host: Dr. Alan Attie
The colloquium will feature invited lecturers and bring together metabolism researchers to share ideas, expertise and resources. Visiting lecturers will present a seminar on their work (time and dates will vary) as well as meet with members of the metabolism community.