Department of Microbiology and Immunology
Beichu Guo, PhD
2003 Ph.D. Department of Immunology, University of Washington
Dr. Guo received his Ph.D. in Immunology from the University of Washington, under the supervision of Dr. David Rawlings, where Dr. Guo studied the proximal signaling complex of antigen receptors and NF-κB activation in B cells. He also elucidated the role of protein kinase C and CARMA1 (CARD11)-mediated NF-κB activation in the growth and survival of B cell lymphomas. Then Dr. Guo joined the laboratory of Dr. Genhong Cheng as a postdoctoral fellow at the Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, UCLA. From 2008-2010, Dr. Guo was also chosen as a Special Fellow by the Leukemia & Lymphoma Society (LLS). His postdoctoral research was involved in two areas: the innate signaling pathways triggered by bacterial or viral infection, and the role of innate immunity and inflammation in autoimmune diseases. At the end of 2010, Dr. Guo became an independent investigator at the Department of Microbiology & Immunology, Hollings Cancer Center, Medical University of South Carolina (MUSC). Research in the Guo laboratory is focused on the role of innate immune system, especially inflammasomes, in autoimmune diseases and cancer. Recently, Dr. Guo has been awarded an American Cancer Society (ACS) Research Scholar Grant for his research on senescence-associated inflammation and cancer progression.
Inflammasomes in tumor microenvironment and cancer metastasis.
Although genetic alternations are critical for cellular transformation and tumor development, emerging evidence indicates that tumor microenvironments exert a significant impact on tumor progression. We are studying the role of inflammasome pathways in tumor microenvironments during cancer initiation, growth and metastasis. We also investigate how inflammasomes contribute to inflammatory and immunosuppressive microenvironments that affect host anti-tumor immunity and conventional cancer therapies.
Senescence-associated inflammation in tumor immunity and tumor progression.
I am particularly interested in the immune response during early stages of tumor development such as oncogenic transformation and oncogene-induced senescence. In response to oncogene activation or DNA damage, cells can enter a state of growth arrest, referred to as cellular senescence. In addition, chemotherapies, and even anti-tumor immune response can induce senescence in normal or tumor cells. Traditionally, cellular senescence has been defined as a barrier against malignant transformation. Paradoxically, recent progress indicates that senescence also has pro-oncogenesis properties. Therefore, understanding the mechanisms regulating tumor-promoting vs. -inhibiting effects of senescence will provide potential strategies for cancer therapies. We will investigate how the crosstalk between senescent cells and innate immune cells influences senescence, SASP and tumor development. Our study will also directly address a key question about the origin of tumor-associated inflammation. Furthermore, we will determine the contribution of therapy-induced senescence to inflammation, cancer recurrence and metastasis.
Innate pathways and inflammasomes in autoimmune diseases.
Our laboratory is also interested in understanding the role of innate immune system, including Toll-Like Receptors (TLRs), interferon pathways and inflammasomes in autoimmune diseases, such as inflammatory bowel diseases (IBD) and multiple sclerosis (MS). Our previous studies revealed a novel immunoregulatory function of TLR-mediated interferon pathways on the innate and antigen-specific immune response. The aim of our current research is to elucidate the mechanisms for the therapeutic efficacy of type I interferon in the treatment of certain cancer and autoimmune diseases. Our recent studies demonstrate that chronic inflammasome activation promotes the development of intestinal inflammation. The aims of this project are to identify downstream mediators of inflammasome/IL-1β in chronic colitis, and to delineate the role of various inflammasomes in the complex interaction of gut epithelial cells, immune cells and microbiota during intestinal inflammation and tumorigenesis.
Recent Publications | Additional Publications
Guo B, Kato R, Garcia-Lloret M, Wahl MI, and Rawlings DJ. Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex. Immunity 13:243, 2000. PMID: 10981967
Sommer K, Guo B (co-first author), Pomerantz JL, Bandaranayake AD, Moreno-Garcia ME, Ovechkina YL, and Rawlings DJ. Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity 23:561, 2005. PMID: 16356855
Oganesyan G, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, Perry A, and Cheng G. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439:208, 2006. PMID: 1630693
Guo B and Cheng G. Modulation of the Interferon Antiviral Response by the TBK1/IKKi Adaptor Protein TANK. J. Biol. Chem. 282:11817, 2007. PMID: 17513714
Chang EY, Guo B (co-first author), Doyle SE, and Cheng G. Cutting Edge: Involvement of the Type I IFN Production and Signaling Pathway in Lipopolysaccharide-Induced IL-10 Production. J Immunology 178(11):6705, 2007. PMID: 17513714
Guo B, Chang EY, and Cheng G. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. Journal of Clinical Investigation 118(5):1680, 2008. PMID: 18382764
Chin A, Miyahira AK, Covarrubias A, Teague J, Guo B, Dempsey PW, and Cheng G. 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. PMID: 20233880
Zhang L, Yuan S, Cheng G, and Guo B. Type I IFN promotes IL-10 production from Th17 cells to suppress autoimmune inflammation. PLos One 6(12):e28432, 2011. PMID: 22163016
Zhang J, Fu S, Sun S, Li Z, and Guo B. Inflammasome activation has an important role in the development of spontaneous colitis. Mucosal Immunology 2014 Jan 29. doi: 10.1038/mi 2014.1. PMID: 24472848
Guo B and Li Z. Endoplasmic reticulum stress in hepatic steatosis and inflammatory bowel diseases (review). Frontiers in Genetics 2014.
The type I IFN pathway constrains Th17-mediated autoimmune diseases.
Inflammasome activation in oncogene-induced senescence.
MUSC Hollings Cancer Center he American Cancer Society Institutional Research Grant
The role of inflammasome activation in sphingosine kinases-mediated breast cancer development.
MUSC COBRE in Lipidomics and Pathobiology Pilot Grant
Senescence-induced inflammasome activation promotes cancer progression.
The American Cancer Society Research Scholar Award