Faculty Directory
DhavalkumarPatel, MD, PhD
Title(s)
- Professor
Department(s)
- Microbiology and Immunology
- Medicine
Education
- B.S., Duke University, 1982
- M.D./Ph.D., Duke University School of Medicine, 1989
- Residency, Duke University School of Medicine, 1989-1991
- Fellowship, Duke University School of Medicine, 1991-1994
- Fellowship, Duke University School of Medicine, 1995-1996
Research Interests
- Chemokines and Leukocyte Migration
- Bioinformatics Integration
- Proteomics
- Genetic Vectors
Research Summary
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 we are 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. We and others have 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.
We are testing the hypothesis that FKN and CX3CR1 regulate the host immune response by affecting effector cell trafficking and function.
We are also 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 GRK 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-GRK system have markedly altered inflammatory responses.
We are dissecting the mechanisms by which ß-arrestin2 and GRK regulate leukocyte trafficking to sites of inflammation.