The laboratory studies the development and maturation of the cellular immune system in mediating antitumor and anti-inflammatory immune responses in the context of chronic inflammation.. The general goals are to use cellular and molecular approaches to investigate the consequences of persistent exposure to interferon-γ (IFN-γ) and how it alters host physiology. To approach this question, we have generated a novel mouse model where a portion of the 3' untranslated region of the mRNA has been changed, resulting in a much more stable mRNA and this will now permit us to understand the consequences of persistent IFN-γ expression on the host. We have backcrossed this change onto the murine C57BL/6 and Balb/c genetic backgrounds and as a consequence have developed new mouse models for lupus, primary biliary cholangitis, ovarian failure syndrome and aplastic anemia. In addition we have now found that male mice may be more susceptible to developing myocarditis upon exercise.   These mice are characterized by low but chronic IFN-γ expression. As a result there is persistent upregulation of IFN-γ inducible genes, resulting in the development of autoimmunity. Overall, our studies represent a cellular and molecular analysis of the consequences of aberrant regulation of cytokine gene expression in lymphoid cells and the effects on the host physiology and immune system development and function. Our studies provide a basis for developing a more complete understanding of the effects of IFN-γ expression during the pathogenesis of autoimmune diseases, cancer and infection and offer a model system for developing treatments to prevent or block disease progression.

Our collaborators include NCI investigators Dan McVicar, and David Wink. In addition we have collaborations with Dr. Eric Gershwin (UC-Davis), Dr. Anthony Filiano (Duke), Dr. Clint Allen (NICHD) and Dr. Guozhen Liu (Australia).