Dr. Genhong Cheng's laboratory studies molecular events involved in host defense against pathogen infections. Cheng and his colleagues have recently identified several gene programs specific for antiviral or antibacterial responses. In some cases, the researchers found that host responses to bacterial infection and viral infection may even be opposite. For example, type I interferon, an essential antiviral cytokine, might play a harmful role in host defense against certain bacterial infection. Cheng's laboratory also is interested in understanding the mechanisms of chemoresistance and developing novel strategies to improve cancer treatment. They have found that many chemotherapy agents commonly used clinically that are supposed to kill tumor cells can actually activate alternative cell survival pathways to protect tumor cells. This phenomenon may represent a potential mechanism of chemoresistance. Furthermore, Cheng and his colleagues found that blocking the NF- B-dependent up-regulation of Bcl-x and Bfl-1 genes can greatly reduce chemoresistance and sensitize chemotherapy-mediated apoptosis. Cheng's laboratory is currently evaluating the possibility of using the combination of NF- B inhibitors and chemotherapy agents for cancer therapy.
Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4239-44. Epub 2012 Feb 27
Iyer SS, Ghaffari AA, Cheng G. Lipopolysaccharide-mediated IL-10 transcriptional regulation requires sequential induction of type I IFNs and IL-27 in macrophages. J Immunol. 2010 Dec 1;185(11):6599-607. Epub 2010 Nov 1
Razani B, Zarnegar B, Ytterberg AJ, Shiba T, Dempsey PW, Ware CF, Loo JA, Cheng G. Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. Sci Signal. 2010 May 25;3(123):ra41.
Guo B, Chang EY, Cheng G. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest. 2008 May;118(5):1680-90.
Zarnegar BJ, Wang Y, Mahoney DJ, Dempsey PW, Cheung HH, He J, Shiba T, Yang X, Yeh WC, Mak TW, Korneluk RG, Cheng G. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol. 2008 Dec;9(12):1371-8. Epub 2008 Nov 9