Chemokines
In order for white blood cells to perform their protective functions, they must migrate to specific anatomic locations. This applies for circulating leukocytes ability to traffic to sites of infection, and for homing to secondary lymphoid organs to present or acquire antigen to coordinate a specific immune response. These two processes occur in four basic steps, as shown in the graphic above. Leukocytes rolling along blood vessels will become activated once they recognize a chemical gradient created by specialized, low molecular weight molecules termed "chemokines." Following activation, membrane bound integrins on the leukocytes transition to a high-affinity state and can now adhere strongly to ICAMs expressed on the endothelial cell surface. Once tightly bound, the leukocytes exit the bloodstream and enter the site of infection or the secondary lymphoid organ through the process of diapedesis.
Our lab has heavily studied one particular chemokine of interest, originally known as monocyte chemoattractant protein-1 (MCP-1) and now referred to as CCL2 in systematic nomenclature. Through biochemical analysis we demonstrated some of the structural requirements for MCP-1 activity and led to the discovery of a potent antagonist which is now in commercial development for clinical use. We have developed an MCP-1-deficient mouse which has helped us to demonstrate MCP-1's essential contributions to diseases such as atherosclerosis and multiple sclerosis. We also use MCP-1 to explore ways in which the chemokine system modulates T helper cell responses.
The most recent work of our lab on this topic has shown that the CCL2/CCR2 interaction is clinically significant in breast cancer. In a HER-2/neu breast cancer murine model, we found that CCL2 acts through CCR2 in the tumor microenvironment to promote carcinoma development. Inhibition of either CCL2 or CCR2 in the signaling pathway was able to decrease chances of tumor neovascularization.
While our lab is not currently working on this project, we invite you to view our literature or contact us with any questions.
Our lab has heavily studied one particular chemokine of interest, originally known as monocyte chemoattractant protein-1 (MCP-1) and now referred to as CCL2 in systematic nomenclature. Through biochemical analysis we demonstrated some of the structural requirements for MCP-1 activity and led to the discovery of a potent antagonist which is now in commercial development for clinical use. We have developed an MCP-1-deficient mouse which has helped us to demonstrate MCP-1's essential contributions to diseases such as atherosclerosis and multiple sclerosis. We also use MCP-1 to explore ways in which the chemokine system modulates T helper cell responses.
The most recent work of our lab on this topic has shown that the CCL2/CCR2 interaction is clinically significant in breast cancer. In a HER-2/neu breast cancer murine model, we found that CCL2 acts through CCR2 in the tumor microenvironment to promote carcinoma development. Inhibition of either CCL2 or CCR2 in the signaling pathway was able to decrease chances of tumor neovascularization.
While our lab is not currently working on this project, we invite you to view our literature or contact us with any questions.