Robert D. Schreiber, Ph.D.
Alumni Endowed Professor
Pathology and Immunology
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.
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Ann Rev Immunol 2004 22:239-360.
Shankaran VJ, Ikeda H, Bruce AT, et al. IFNg and lymphocytes prevent primary tumor development and shape tumor immunogenicity. Nature 2001 410:1107-1111.
Yin L, Wu L, Wesche H, et al. Defective lymphotoxin-b receptor-induced NFkB transcriptional activity in NIK-deficient mice. Science 2001 291:2162-2165.
Rodig SJ, Meraz MA, White JM, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of Jaks in cytokine-induced biologic responses. Cell 1998 93:373-383.
Meraz MA, White JM, Sheehan KFC, et al. Targeted disruption of the STAT1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 1996 84:431-442.
Last Updated: 8/4/2011 12:10:54 PM