Phone: (409) 747-0789
Fax: (409) 747-0762
Email: sktseng@utmb.eduEducation: PhD, 1997, University of Arkansas for Medical Sciences
MS, 1981, Mississippi State University
BS, 1976, National Chung-Hsing University, Tai-chung, Taiwan
Overview: Host innate immunity to and the
pathogenesis of emerging and re-emerging RNA viral infections (SARS,
RVF, and Avian Influenza).
Virology and viral immunology - Ebola virus; Rift Valley Fever; Hantavirus; Nipah virus; Hepatitis C
Research Interests
- 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 virusses 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 NFκB, 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), Rift
Valley Fever virus (RVFV, a BSL-3+ pathogen), Junin virus (JV, a BSL-4
pathogen), Dhori virus, a tick-born Orthomyxovirus, which is a BSL-2
pathogen sharing a strikingly similar pathogenetic mechanism with avian
influenza H5N1 virus in mice. To ensure the success of our studies, we
adopt a two-stage strategy for the proposed studies. Specifically, we
first perform in vitro studies using virally permissive and
pathologically relevant human cells, including lung epithelial cells
(SARS, Dhori virus), human umbilical vascular endothelial cells (HUVEC)
and hepatocytes (RVF, Dhori), along with two of the most implicated
classic innate immune cells, e.g., primary human macrophages and
dendritic cells (RVFV and JV). Once specific signaling pathway(s) and
cellular targets are identified, we will use suitable animal models for
the verification purpose. In this regard, experimental infection of mice
has been used successfully as animal models. Particularly, we have been
using transgenic mice expressing hACE2 (human angiotensin-converting
enzyme 2), the receptor for SARS-CoV, as the animal model for SARS-CoV.
We also use mouse-adapted SARS-CoV, designated MA-15, to infect wild
type and various strains of selected gene knockout (KO) mice, aiming at
dissecting the mechanism of host innate immunity against SARS-CoV and/or
immune-mediated diseases. 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. Our research is currently supported in part by grants and
contracts from the National Institutes of Health, and other
Pharmaceutical industries.
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