Research Interests:
The NF-kappa B proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and cell proliferation. A main focus of research in my laboratory is to understand the specific role played by different NF-kappa B subunits in regulating inflammatory and immune responses. These closely linked responses play a crucial role in protecting us from pathogens such as bacteria and viruses. However, impaired regulation of these responses also underlie many human ailments, including autoimmune disease and cancer. We are particularly interested in the role played by NF-kappa B proteins in dendritic cells (DCs) and T lymphocytes. Working together, these two cell types perhaps play the most important role in initiating an immune response. DCs capture bacterial and viral antigens, a process that also induces DC activation. These antigens are displayed on the surface of DCs, where they are recognized by the T cell receptor (TCR) present on T cells. In addition, various co-stimulatory molecules and cytokines expressed by activated DCs further help induce T cell proliferation and effector function. Through both direct and indirect mechanisms, T cells help eliminate infectious agents. In addition, there is great promise in harnessing the power of DCs in activating T cells capable of recognizing and destroying cancerous tissue.
Our studies utilize mice in which different subunits of NK-kappa B have been ?knocked-out?. Recent studies from my laboratory have shown that TCR engagement provides the primary NF-kappa B activating signal in T cells. Our in vitro and in vivo studies have further shown that NF-kappa B is essential for inducing cell cycle progression and survival of T cells. We are currently investigating the role played by different NF-kappa B subunits in generating effector and memory T cells, as well as their roles in modulating T cell responses in autoimmunity and cancer. In DCs, we have found essential roles for different NF-kappa B subunits in regulating DC development, survival and cytokine production. Current projects in the laboratory include investigation of mechanisms by which different NF-kappa B subunits specifically regulate genes involved in inflammation or immunity. For these studies, we are also utilizing techniques for genome wide analysis of gene expression in DCs. A better understanding of how different NF-kappa B subunits regulate unique aspects of DC function can open up new avenues for modulating DC function in infection, autoimmunity and cancer.