Academic Background:
Research Associate/Senior
Postdoctoral
Ph.D. in Pharmacology
M.S. in Immunology
M.D. |
Scripps Research Institute, La Jolla, 1999-2003
National Institutes of Health (NIH), 1997-1999
Louisiana State University (LSU), 1997
Second Military Medical University, China, 1988
Second Military Medical University, China, 1983 |
Research Interests:
Cytokines are the signaling molecules in neuro-immune communication and
are intimately involved in brain physiology and pathophysiology. Our
goals are to elucidate what role these molecules play in neurological
and neuropsychiatric disorders as well as normal neurodevelopment. Our
current focus is on interferons (IFNs). Type I interferon IFN-a,
for example, is a key first line anti-viral cytokine through Janus
kinase (JAK)/signal transducer and activator of transcription (STAT)
signaling pathway. As the most used cytokine clinically, type I IFN has
been successfully used to treat patients with chronic HCV infection, a
number of different malignancies and relapsing-remitting multiple
sclerosis. In addition to its anti-viral, anti-tumor and
immunoregulatory activity, however, IFN-a
has also been implicated in the pathogenesis of several CNS disorders,
such as NeuroAIDS (HIV dementia), CNS lupus, Aicardi-Goutières syndrome
and Cree encephalitis. Furthermore, chronic systemic therapy of IFN-a
in patients results in severe neuropsychiatric side effects including
depression, anxiety and cognition impairments.
Our current study is to elucidate the mechanisms of neuropathogenic/neurotoxic
actions of interferons (IFNs) employing integrated neurobehavioral,
neuropathological, pharmacological, molecular and genetic approaches.
There are two projects in progress in our laboratory: one project is to
develop a mouse model for human depression resulting from chronic IFN-a
therapy in which to investigate the neurobehavioral deficits due to
chronic IFN-a
treatment and elucidate the underlying mechanisms. The other project is
to investigate interferons and IFN signaling in cerebellar development
and to explore the possible direct link between infection/inflammation
and medulloblastoma, the most common pediatric malignancy in the brain.
Techniques Used in Laboratory:
RNase protection assay (RPA); Western blot; immunohistochemistry;
in situ
hybridization; primary neuronal culture; global gene profiling (microarray
analysis); application of genetically manipulated animals (both
transgenic & knockout mice); enzyme-linked immunosorbent assay (ELISA);
radioimmunoassay (RIA); depression- and anxiety-like behavior battery.
Representative Publications:
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Wang, J.
and Campbell, I.L. (2005). Innate STAT1-dependent genomic
response of neurons to the anti-viral cytokine alpha interferon.
J. Virology 79:8295-8302. |
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Wang, J.,
Lin, W., Popko, B. and Campbell, I.L. (2004). Induced production
of interferon-g
in the developing brain causes cerebellar dysplasia with
activation of the sonic hedgehog pathway. Mol. Cell. Neurosci.
27:489-496. |
|
Dunn, A. J. & Wang, J. (2004). Cytokines and the brain.
In: Elsevier’s Encyclopedia of Neuroscience (Ed. Adelman,
G. and Smith, B.H.), Elsevier Science Press, 3rd Edition. |
|
Wang, J.,
Pham-Mitchell, N., Schindler, C. and Campbell, I.L. (2003).
Dysregulated sonic hedgehog signaling and medulloblastoma
consequent to IFN-a-stimulated
STAT2-independent production of IFN-g
in the brain. J. Clin. Invest. 112:535-543 |
|
Wang, J.,
Schreiber, R.D. and Campbell, I.L. (2002). STAT1 deficiency
unexpectedly and markedly exacerbates the pathophysiological
actions of IFN-a
in the CNS. Proc. Natl. Acad. Sci. USA. 99:16209-16214. |
|
Wang, J.,
Valerie, C.A. and Campbell, I.L. (2002). Cytokines and
chemokines as mediators of protection and injury in the central
nervous system assessed in transgenic
mice. Current Topics Microbiol. Immunol. 265:23-48 |
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Griffiths, M.M., Wang, J., Joe, B., Dracheva, S.,
Kawahito, Y., Shepard, J.S., Reese, V.R., McCall-Vining, S.,
Hashiramoto, A., Cannon, G.W., Remmers, E.F. and Wilder, R.L.
(2000). Identification of four new quantitative trait loci
regulating arthritis severity and one new quantitative trait
locus regulating autoantibody production in rats with
collagen-induced arthritis. Arthritis Rheum.
43:1278-1289. |
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Dracheva, S.V., Remmers, E.F., Chen, S., Chang, L., Gulko, P.S.,
Kawahito, Y., Longman, R.E., Wang, J., Du, Y., Shepard,
J., Ge, L., Joe, B., Kotake, S., Salstrom, J.L., Furuya, T.,
Hoffman, J., Cannon, G.W., Griffiths, M.M. and Wilder, R.L.
(2000). An integrated genetic linkage map with 1,137 markers
constructed from five F2 crosses of autoimmune disease-prone and
-resistant inbred rat strains. Genomics 63:202-226. |
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Wang, J.
and Dunn, A. J. (1999). The role of interleukin-6 in the
activation of the hypothalamo-pituitary-adrenocortical axis
induced by endotoxin and interleukin-1b.
Brain Res. 815:337-348. |
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Wang, J.
and Dunn, A. J. (1998). Mouse interleukin-6 stimulates the HPA
axis and increases brain tryptophan and serotonin metabolism.
Neurochem. Internl. 33:143-154. |
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