• 86240
1972 …2023

Research activity per year

Personal profile

Research interests

Our research focuses on elucidating the molecular cell biology of cytokine receptor signaling and on defining the role of cytokines and lymphocytes in controlling tumor development. First, we continue to pursue our long-standing interest in cytokine receptor signaling through the analysis of the structure and function of the receptors for interferon-gamma (IFNg), interleukin-10 (IL-10) and tumor necrosis factor (TNF). Much of this work now involves the use of gene ablation and gene profiling techniques to generate mice that lack particular receptor signaling components and to characterize the physiologic outcomes of receptor engagement. This approach has led to the discovery of a novel alternative pathway of IFNg signaling and has helped to clarify the roles of the JAK-STAT and NF-kB signaling pathways in development of cytokine-induced biologic responses. Second, we have made a substantial commitment to defining the role of the immune response in controlling tumor development. Using genetically engineered mice that are insensitive to IFNg and/or that lack lymphocytes, we have shown that the immune system indeed protects the host against development of carcinogen-induced and spontaneous tumors. In this process, IFNg functions, at least in part, to enhance the immunogenicity of developing tumors and thereby facilitates their recognition by T lymphocytes. However, the collaborative actions of IFNg and lymphocytes sometimes favor the selection of tumor variants with reduced immunogenicity that are more capable of surviving in an immunocompetent host. Thus, tumors are imprinted by the immunological environment in which they develop, a process that we have termed “tumor editing”. Current work is aimed at defining the molecular basis of tumor editing and in understanding the precise roles of IFNg and lymphocytes in this process.

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  • PhD/MSTP Students


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