Cancer Institute A national cancer institute
designated cancer center

Structural Studies of T Cell Receptors, Co-receptors, MHC and their Ligands

  Structural and functional biology of cell surface receptor signaling

Christopher Garcia's laboratory studies the structural and functional basis of receptor/ligand interactions in systems which are relevant to human health and disease. His investigations are aimed at understanding the molecular recognition properties governing the interactions of receptors with their ligands, and the subsequent molecular events which couple ligand recognition to receptor activation.

Functional Approaches

The structural studies are complemented by functional approaches using molecular biology and protein engineering to dissect the structural information, design new or altered proteins with modified specificities and activities, and ultimately contribute to the development of proteins or molecules with therapeutic potential. Molecules currently under study include receptors of the immune system involved in the immune response to cancer (T cell receptors, co-receptors, MHC, cytokines), and membrane proteins (chemokine receptors).

Clinical Applications

Currently, Dr. Garcia is initiating efforts to begin to exploit his recent structural studies of IL-2, and IL-6 receptor complexes as potential therapies in a variety of cancers. With regard to IL-2 his laboratory is exploring the potential to engineer the cytokine to have reduced toxic side effects by focusing its binding towards one of the two forms of its receptor on T cells.

In the IL-6 system, Dr. Garcia is attempting to computationally design small molecules that will antagonize the interaction between IL-6 and its receptor. Promising leads will be tested in vitro, and then in cellular and murine animal models for efficacy, in collaboration with members of the Cancer Center, such as Dr. Engleman.

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