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Sanjeev Choudhary, PhD

Assistant Professor, Department of Internal Medicine,
Division of Endocrinology,
Sealy Center for Molecular Medicine

Phone: (409) 772-7571

Sanjeev Choudhary, PhD

Research Interests

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.

Selected Publications

  1. 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, 2003.

  2. 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.

  3. 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.

  4. 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.

  5. Choudhary, S. and Gill, K.D. Protective effect of nimodipine on dichlorvos-induced delayed neurotoxicit. Biochem. Pharmacol. 62: 1265-1272,2001.

  6. 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.

  7. 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).

  8. 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).

  9. 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).