Dr. Tseng's research interests include:
My primary research is focused on understanding how RNA viruses trigger the host immune responses and how animals defend against emerging and re-emerging viruses. Specifically, we study the molecular and cellular interplays whereby the innate immune responses are initiated and regulated and how an unregulated innate immunity leads to diseases and mortality. We are particularly interested in dissecting the antiviral signaling pathways by which pathologically relevant host cells mount innate immune responses to invading viruses. We are also interested in how viruses evade the host defense system. The ultimate goal of our studies is to understand and identify novel molecules of the innate immune system as targets for preventive and therapeutic intervention against RNA viral infections.
RNA virus infection is detected by the host cells through either toll-like receptor (TLR)-3 and -7/8, which are located primarily on the endosomal membrane, or the cytosolic RNA helicase proteins RIG-I (retinoic acid-inducible gene I) and MDA5 (melanoma differentiation antigen 5), which transmitting activation signals to the cytosolic adaptor TRIF, MyD88, and MAVS/IPS, respectively, that ultimately leads the activation of an array of antiviral genes, including type I interferons (IFNs), inflammatory cytokines and chemokines, and many interferon-stimulated genes (ISGs), via at least three overlapping antiviral pathways mediated by transcription factors NF?B, interferon regulatory factor-3 (IRF-3), and ATF2/cJUN intermediate signaling molecules. Among various RNA viruses, we are currently focusing on dissecting the antiviral signaling pathways induced by severe acute respiratory syndrome coronavirus (SARS-CoV, a BSL-3 pathogen) and Rift Valley Fever virus (RVFV, a BSL-3+ pathogen). In addition to the wild-type virus, we also generate recombinant viruses by using reverse genetics. Both the in vitro and suitable animal models are used for our studies. Specifically, we first perform in vitro studies using virally permissive and pathologically relevant human cells, including lung epithelial cells (SARS-CoV), hepatocytes (RVFV), and three of the most implicated classic innate immune cells, e.g., primary human macrophages (Mø) and dendritic cells (DC), and natural killer (NK) cells. Once specific signaling pathway(s) and cellular targets are identified, we will use suitable animal models, including transgenic and/or gene knockout (KO) mice, for the verification purpose and beyond. Various state-of-art approaches involving virology, immunology, biochemistry, molecular biology, and genetics are used to establish and characterize cell lines/clones with specific gene KO or knock down (KD) (i.e., loss-of-function) or constitutive expression (i.e., gain-of-function) phenotypes, and identify the role(s) of selected genes in the host antiviral defense. We are also interested in evaluating the impact of the cellular interplays on the pathogenesis of viruses in vitro, via using two- and/or three-dimensional culture systems. We are also actively involved in the development and evaluation of preventive and therapeutic strategies against SARS and RVFV.