Project 4 (Sur, S.)

Contact Information: Sanjiv Sur, MD Professor in Internal Medicine 8.104 MRB Department of Internal Medicine-Allergy UTMB 301 University Blvd. Galveston, TX 77555-1083 Email:   sasur@utmb.edu Dr. Sur's bio...
Project Summary: Dr. Sur will pursue the hypothesis is that reactive oxygen species (ROS) generated by interaction of intrinsic NADPH oxidases in pollens with NADPH in airway lining fluid provides a critical second signal that activates MAP kinases and induces of expression of genes in the lungs that augment mucin production, airway inflammation and AHR in allergic asthma. Three specific aims are proposed: Activation of MAP kinases by Signal 2 mediates induction of genes and gene products that facilitate trafficking of dendritic and Th2-cells and augment mucin production in airway epithelial cells. Elevated levels of 4-HNE and GSSG in the lungs directly potentiate airway inflammation, AHR and mucin production in naïve mice, and induce specific genomic signatures in the lungs. MAP kinases regulate subsets of Signal 2-sensitive global genomic signature in lungs. This project will define the molecular mechanisms of signal 2-induced pathways and will fundamentally shift our understanding of the mechanisms of initiation of allergic inflammation in asthma from a one-signal paradigm to a novel two-signal pathway.

Recent Publications:

1. BK Choudhury, J.S. Wild, D. Klinman, N Dharajiya, I Boldogh, R. Alam, S. Sur. In vivo role of p38 MAP kinase in mediating the anti-inflammatory effects of CpG DNA in a mouse model of asthma. Journal of Immunology 2002, 169:5955-5961.
2. Cen O, Gorska MM, Stafford SJ, Sur S, Alam R. Identification of Unc119 as a novel activator of SRC-type tyrosine kinases. J Biol Chem 2003 Mar 7;278(10):8837-45.
3. Leonard PA, Sur S. IL-12: Potential Role in asthma therapy. BioDrugs 2003;17(1):1-7.
4. Srivastava A, Sur S, Trocme SD. The role of eosinophils in ocular allergy. Int Ophthalmol Clin 2003;43(1):9-25.
5. Gorska MM, Stafford SJ, Cen O, Sur S, Alam R. Unc119, a novel activator of lck/fyn, is essential for T cell activation. J Exp Med. 2004 Feb 2;199(3):369-79.
6. Bleobaum RM, Grant JA, Sur S. Immunomodulation: the future of allergy and asthma treatment. Curr Opin Allergy Clin Immunol. 2004 Feb; 4(1):63-7.
7. Boldogh, I., A. Bacsi, B.K. Choudhury, N. Dharajiya, R. Alam, T. Hazra, S. Mitra, R. Goldblum, and S. Sur ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation J. Clin. Invest., Aug 2005; 115: 2169 - 2179.
8. Bacsi, A., Choudhury, B.K., Dharajiya, N., Sur, S., and Boldogh, I. Impact of pollen-mediated oxidative stress on hypersensitivity reactions and lat-phase inflammation in allergic conjunctivitis. J. Allergy Clinical Immunology, 2005 in press.