James F. Miller, Ph.D.

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The primary focus of my research is to unravel basic cellular and molecular mechanisms that underlie T cell recognition of antigen. T cell activation is associated with a dramatic reorganization of cell surface receptors, cytosolic signaling molecules, and cytoskeletal elements within the adhesion complex that forms between a T cell and antigen presenting cell. This has been termed the immunological synapse.

We have found that the selective engagement of adhesion and costimulatory molecules can differentially regulate the organization of proteins within the immunological synapse; this can lead to further changes in gene expression. We are currently using in vitro mutagenesis, recombinant fusion proteins, and retroviral gene transfer combined with biochemical and microscopic analysis, including live cell imaging, to identify the factors and interactions that determine the specific localization of proteins within the immunological synapse and how this localization impacts on signal integration and regulation of gene expression.

In addition, we have found costimulation through the integrin LFA-1 can inhibit the generation of Th2 effector T cells. We are currently evaluating the biochemical and molecular events that control this cell lineage commitment event and how these events are regulated by LFA-1 and other costimulatory molecules.

Current Appointments

• Professor - Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology (SMD)