Fong Lab
Director: Alan Fong, PhD
The Fong Lab is actively investigating Chemokines.
Chemokines and their receptors are intimately involved in regulating organ-specific leukocyte trafficking and inflammation. We have been studying the roles that chemokines and their G-protein coupled receptors (GPCRs) play in leukocyte trafficking from the blood into tissues, with an interest in inflammatory diseases including arthritis, asthma and atherosclerosis.
One of the chemokines that the Fong lab is using to dissect the mechanisms of leukocyte recruitment to sites of inflammation is fractalkine (FKN, CX3CL1), a membrane-tethered chemokine on activated endothelium. Its receptor CX3CR1 is expressed on effector leukocytes including monocytes, NK cells and perforin/granzyme containing T cells, and on vascular smooth muscle cells. The Fong lab has identified critical roles for CX3CR1 in coronary artery disease, cardiac transplant rejection and anti-tumor responses. In addition to the chemotactic and other functional properties attributed to chemokines, we have shown that FKN and CX3CR1 have remarkable cell adhesion properties that may contribute to cell migration and function. A hupothesis is currently being tested to determine if FKN and CX3CR1 regulate the host immune response by affecting effector cell trafficking and function.
In addition the Fong lab is studying the signal transduction pathways that lead to chemotaxis. Chemokine receptors are G-protein coupled and are regulated by the -arrestin - G receptor kinase (GRK) system. We have shown that -arrestin-2 and GRKs are critical regulators of chemotaxis with pleotropic roles depending on the receptors being activated. Our studies and those of collaborators are showing that mice deficient in specific components of the ßarrestin-GRKs system have markedly altered inflammatory responses. We are dissecting the mechanisms by which ß-arrestin2 and GRKs regulate leukocyte trafficking to sites of inflammation.