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HANDEL LAB

Skaggs School of Pharmacy and Pharmaceutical Sciences

University of California, San Diego

La Jolla, CA

                             RESEARCH 

I. Structure and Function of Chemokines. Research in the Handel lab is focused primarily on the structure and function of chemokines and chemokine receptors. These proteins control the migration of cells in the context of development, immune surveillance, and inflammation.  Inappropriate utilization or regulation of chemokines/receptors is also associated with numerous diseases including inflammatory diseases, atherosclerosis, HIV, and malaria.  We are particularly interested in the function of chemokines in cancer. The following figure illustrates some of the important interactions of chemokines in cell migration which includes chemokine oligomerization, binding to cell surface glycosaminoglycans, and binding to their G protein-coupled receptors (GPCRs). Virus also produce chemokine binding proteins to neutralize the functions of chemokines by interfering with all of these interactions.

 

 

 

 

 

 

 

 

 

To learn more about our structural studies, click on the following links:

Structural and Functional Studies of Chemokines, Chemokine GPCRs, and Viral Chemokine Binding Proteins

II. Chemokine Receptor Signaling in Cancer. An additional area of research involves examining the contribution of chemokines to cancer. We are especially interested in chemokine-mediated survival signaling in both breast cancer and chronic lymphocytic leukemia (CLL). To learn more about these topics click on the following links:

The Role of Chemokines/Receptors in Breast Cancer

The Role of Chemokines in Chronic Lymphocytic Leukemia

 III. Computational Protein Design.  A third area of research involves computational protein design.  We have developed a protein design algorithm called EGAD Library which contains a modular architecture for customizing energy functions and search algorithms for the problem at hand. We have recently used EGAD in the design and analysis of protein-protein interactions using the beta-lactamase/beta-lactamase inhibitor complexes as model systems. Click on the following link to learn more:

Protein Design