Biomedical Sciences Graduate Program | University of California, San Francisco

Our laboratory studies chemokines and chemokine receptors. Chemokines are small, heparin-binding proteins and are potent chemoattractants of leukocytes. Chemokines are thought to be involved in a wide spectrum of human disease, including atherosclerosis and AIDS. We were the first to clone CCR2, the receptor for MCP-1. Much of the work in the laboratory over the past several years has focused on the elucidation of ligand binding domains and signal transduction pathways of this receptor. We have also devoted attention to CCR5, a coreceptor for leuko-cyte infection by HIV-l strains with a preference for macrophages. We have shown that HIV-1 interacts with multiple extracellular domains of CCR5, and have further shown that signal-ing by CCR5 is not critical for coreceptor activity.

We have recently created CCR2-deficient mice.These mice are phenotypically normal when raised under aseptic conditions, but exhibit profound defects in recruitment of monocytes/ macrophages to sites of inflammation or injury. During the past year, we crossed the CCR2-deficient mice with apo-E knockouts, a line of mice genetically altered to develop severe atherosclerosis. Preliminary results suggest that the absence of CCR2 confers protection against atherogenesis in these double-knockout animals.