LiveWorld Transcripts

Bio Online presents

Thomas J. Schall, Ph.D., James Campbell, Ph.D. and John P. Moore, Ph.D.
Chemokines and their Receptors

December 14, 2000

Scientists discuss the biology and therapeutic potential of chemokines and their receptors.

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BioOnline: Welcome to Bio Online's live discussion on Chemokines and Their Receptors! Chemokines are a family of small molecular weight proteins whose primary function is to control the migration of immune cells through lymphoid organs and other tissues. They exert their effects through binding to seven-transmembrane G-protein coupled receptors on the target cell's surface. It has recently become clear that chemokines and their receptors play an important role in a wide variety of diseases including inflammatory disorders, cancer and infectious diseases, such as HIV. . This evening, our guests will focus on the latest research on the biology of chemokines and chemokine receptors and their potential as drug targets and therapeutic agents. Now, I would like to introduce our panelists. We are very fortunate to have with us: Thomas J. Schall, Ph.D., the founder, President and CEO of ChemoCentryx, a biotech company specializing in the biology of chemokines. He is leading their efforts to develop new therapeutics for the treatment of various inflammatory and infectious diseases as well as cancer based on a concerted and comprehensive study of chemokine biology. James Campbell, Ph.D., an assistant professor at Harvard University. He made pivotal contributions to our understanding of the role of chemokines in tissue-specific and microenvironment-specific lymphocyte homing. John P. Moore, Ph.D., Professor of Microbiology and Immunology at Joan and Sanford I. Weill Medical College of Cornell University. The focus of his studies is the process by which HIV fuses with its target cells. He is developing new antiviral agents that target chemokine receptors, essential co-receptors for HIV entry. Welcome! You are each focused on different aspects of chemokine biology. Could you each describe your interest in chemokines and give an example of a recent advance in your area that you are most excited about?

Tom: Thank you. Yes, we are certainly focused in trying to understand for the first time, more of the global aspects of how the chemokine system is tied together. For many years, we and many others have been focusing on specific receptor ligand interactions, sometimes ignoring how those receptor interactions are networked to other receptor interactions within the chemokine system. We're attempting now to create a kind of global profile of the chemokine system by looking simultaneously at the action of many dozens of chemokines on different cellular targets. And in compiling such a map, we hope to gain some insight into the critical parts of that network that are involved in important human diseases. It's kind of a systems approach to chemokine biology, rather than a bimolecular approach to chemokine biology.

James: My main interests are in understanding the interactions between lymphocytes and endothelium that lead to extravasation from the blood into tissues in which chemokines seem to be a major player. Also, I'm interested in differences between lymphocyte subsets that contribute to tissue specific extravasation, and finally, the involvement of chemokines in organization of complex microenvironments within tissues. I think recently, differential chemokine receptor expression has found to be associated with tissue specific homing, and these are the recent findings that I find most exciting right now. For example, the association of CCR4 and its ligand, the chemokine tarc -- and the reciprocal association of chemokine receptor CCR9, and its ligand teck, with intestinal homing.

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