Dr. Tseng's research interests include:
- Pathogenesis of emerging and re-emerging RNA viruses
- Innate antiviral signaling pathways against viral infections
- Immune evasion of RNA viruses
- Cytokines and inflammation
- Antivirals and vaccine strategies against RNA viruses of host innate
immunity
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 NFkB,
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
(Mac) 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.
Search PubMed for Dr. Tseng's publications.