My research interest is to understand the mechanism of Respiratory
Syncytial Virus (RSV)- induced airway inflammation. It is widely
appreciated that airway inflammation is an important pathogenic feature
of asthma and considered responsible for many of the clinical
manifestations of the disease. In fact, anti-inflammatory drugs are now
considered mainstay long-term control agents. Understanding the
mechanisms controlling cellular infiltration in the lung, therefore, has
an important significance in the improvements in asthma prevention and
control. RSV, a member of the Paramyxoviridae family of RNA viruses, is a
leading cause of epidemic respiratory tract infection in children in
the United States and worldwide. RSV has generated intense research
interest because it infects virtually 100% of children in the first few
years of their life. Although, the mechanism underlying RSV-induced
airway disease is largely unknown, experimental evidence suggests that
increased production of cytokines and chemokines by the RSV-infected
epithelium could be the crucial determinant of disease severity. RSV
activates a master regulator of inflammation, nuclear factor-?B (NF-?B),
a transcription factor responsible for the production of many of these
genes. We made a novel observation that RSV increases the kinase
activity and the expression of NF-?B inducing kinase (NIK), a kinase
important in viral-induced NF-?B activation. For the first time, we
have shown that RSV infection activates NF- B by both canonical and
non-canonical NF- B activation pathways in a temporally defined cascade.
Our findings indicated that NIK may play a central role in RSV-induced
inflammation, being essential for 100-kDa NF- B2 processing into p52,
forming nuclear complexes with p52, and influencing early NF-
B-dependent chemokines and cytokines expression. We also made a novel
observation that RSV not only leads to the transient nuclear
translocation of NIK, but also forms a ternary complex with NF-kB2/p52
and the CBP/p300 coactivator. My present research work is focused on
understanding the function of nuclear NIK complexes and their role in
NF-?B dependent inflammatory genes expression
Since, Inflammation is also a common denominator which links insulin
resistance, atherosclerosis, dyslipidemia, and excessive glucose
metabolism in type 2 diabetes, and a recent report suggesting importance
of NIK in the development of insulin resistance in adipocytes, we are
developing cell and animal model system to study NIK mediated insulin
resistance in muscles in response to diabetic stimuli and its role in
diabetic complications such as diabetic nephropathy.
- Choudhary, S., Srivastava, S., Srivastava, S.K., and Ansari,
N.H. Metabolism of 4-hydroxynonenal in rat lens and human lens
epithelial cells. Invest. Ophthamol. & Vis. Sci. 44(6) : 2675-2682,
- TianLin, Xio., Choudhary, S., Salauddin S., and Ansari, N.H.
Involvement of oxidative stress in cisplatin- induced apoptosis in
LLC-PK1 cells J. Toxicol. Environ. Health. 66(5):469-479, 2003.
- Choudhary, S., Zhang, W., Zhou, F., Andley, U.P., Campbell, G.,
Chan, L.L., Thompson, E.B., and Ansari, N.H. Cellular lipid peroxidation
end products induced apoptosis in human lens epithelial cells. Free
Radical Biol. Med. 32(4): 360-369, 2002.
- Choudhary, S., Raheja, G., Gupta, V., and Gill K.D. Possible
involvement of dopaminergic neurotransmitter system in
dichlorvos-induced delayed neurotoxicity J. Biochem. Mol. Biol.
Biopysic. 6(1): 29-36, 2002.
- Choudhary, S. and Gill, K.D. Protective effect of nimodipine on
dichlorvos-induced delayed neurotoxicit. Biochem. Pharmacol. 62:
- Choudhary, S., Joshi, K., and Gill, K.D. Possible role of
enhanced microtubule phosphorylation in dichlorvos induced delayed
neurotoxicity in rat. Brain Res. 897: 60-70, 2001.
- Choudhary, S., Xiao, T.L., Zhang, W,Chan, L.L., Vergara, L.A.,
and Ansari, N.H. Toxicology and detoxification of lipid-derived
aldehydes in retinal pigmented epithelial cells. Toxicol. Appl.
Pharmacol. (in press).
- TianLin, Xio., Choudhary, S., Vergara, L.A., and Ansari, N.H.
Modification of Cytoskeletal proteins by lipid-derived aldehydes in the
lens epithelial cells. The Tissue Res. (in press).
- Choudhary, S., Xiao, T.L., Srivastava, S., Nees, D.,
Piatigorsky, J, and Ansari, N.H. Role of Aldehyde dehydrogenase isozymes
in the defense of rat lens and human lens epithelial cells against
oxidative stress. Invest. Opthamol. Vis. Sci. (accepted).