Department of Microbiology and Immunology
Microbiology and Immunology
2004-2009 Postdoctoral Fellow, Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles2003 Ph.D. Department of Immunology, University of Washington
Our laboratory has wide-ranging interests in understanding the molecular and cellular mechanisms for the therapeutic efficacy of type I interferon (IFN) in cancer and autoimmune diseases. Type I IFNs, containing multiple IFNα members and a single IFNβ, not only function as the first line of defense against viral infection, but also have a variety of immunomodulatory activities on both innate and adaptive immune cells. As a result, IFNα/β have been used clinically to treat autoimmune diseases such as multiple sclerosis, and various malignancies including myeloid leukemia and solid tumors. However, the underlying mechanism responsible for the therapeutic effects of IFN is poorly understood.
Innate immune pathways in modulating Th17-associated inflammatory and autoimmune diseases. My research focuses on the role of the Toll-Like Receptor (TLR)-mediated signaling and gene expression networks in regulating Th17 differentiation and its associated inflammatory and autoimmune diseases. TLR signaling is not only important for innate immune responses, but also critical for the initiation and directions of adaptive immune responses, including differentiation of Th17 cells, subtype of CD4+ T helper cells identified recently. Th17 cells have been shown to have important roles for host defense against infection of certain pathogens, whereas elevated Th17 responses are linked to many autoimmune and inflammatory diseases. Our recent studies revealed a novel immunoregulatory or immunosuppressive function of TLR-mediated IFN induction pathway on the innate and antigen-specific immune response. The goal of this research project is to elucidate the mechanisms by which TLR pathways regulate Th17 cell differentiation and to modulate Th17-associated autoimmune and inflammatory diseases through activation of type I interferon pathways.
Effects of the type I interferon pathway in cancer immunotherapy. Another major focus of research projects in our laboratory is to determine the role of innate immunity in tumor immune surveillance, as well as to develop novel immune-based therapeutics. The host immune response to tumors is dedicated by the balance between tumor immune surveillance and tumor-promoting inflammation. We will investigate how the tumor microenvironment and tumor development are modulated by the innate immune system, particularly by type I IFN signaling and induction pathways. We will utilize several animal models, including lymphoma and prostate cancer, to determine the roles and mechanisms of type I IFN in cancer immunity. We will also explore the possibility of harnessing distinct innate immune pathways to selectively modulate tumor-associated inflammation and to promote tumor immunity. Finally, we are interested in understanding the role of inflammation in the development of cancer stem cells.
Recent Publications | Additional Publications
Arnold Chin, Andrea K. Miyahira, Anthony Covarrubias, Juli Teague, Beichu Guo, Paul Dempsey, Genhong Cheng. Toll-like Receptor 3-mediated suppression of TRAMP prostate cancer demonstrates the critical role of type I Interferons in tumor immune surveillance. Cancer Research 70:2595, 2010.
Aparna Subramanian, Beichu Guo, Matthew D. Marsden, Zoran Galic, Scott Kitchen, Amelia Kacena, Helen J. Brown, Genhong Cheng and Jerome A. Zack. Macrophage differentiation from embryoid bodies derived from human embryonic stem cells. Journal of Stem Cells 4:19, 2009.
Beichu Guo, Elmer Y. Chang and Genhong Cheng. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. Journal of Clinical Investigation 118:1680, 2008.
Elmer Y. Chang, Beichu Guo (co-first author), Sean E. Doyle, and Genhong Cheng. Involvement of the Type I IFN Production and Signaling Pathway in Lipopolysaccharide-Induced IL-10 Production. J. immunology (Cutting Edge) 178(11):6705, 2007.
Gagik Oganesyan, Supriya Saha, Beichu Guo, Jeannie He, Arash Shahangian, Brian Zarnegar, Andrea Perry and Genhong Cheng. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439:208, 2006.
Karen Sommer, Beichu Guo (co-first author), Joel L. Pomerantz, Ashok D. Bandaranayake, Miguel E. Moreno-Garcia, Yulia L. Ovechkina, and David J. Rawlings. Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity 23:561, 2005.
Title: K22 Career Development Award
Funding Period: 2010-2012