University of South Florida

Cancer Biology Ph.D. Program at the

Shyam S. Mohapatra, Ph.D. Professor, Department of Internal Medicine                (Allergy and Immunology) Director of Basic Research, Joy McCann Culverhouse Airway Disease Center E-mail: smohapat@health.usf.edu Phone: (813) 974-8568

Training
Ph.D.: Australian National University, Canberra
Postdoctoral Fellowships: University of Bielefeld, Germany; McGill University, Montreal, Canada

Research Interests
Current research at the Airway Disease Center is directed toward prophylactic and therapeutic modulation of upper and lower airway diseases, including respiratory syncytial virus- induced asthma and lung cancer using gene expression therapy. The lab has developed specific expertise in designing viral and non-viral vectors for gene transfer and delivering genes by novel methods into mammalian cells in vitro and in vivo. These vectors are used to test the effect of increasing or decreasing the expression in the lung of the therapeutic genes in various model systems of specific lung diseases including lung cancer. To date, the vectors used include plasmid vectors for the two classes of vaccine vectors have been designed: (1) vectors for expression of the appropriate antigen(s) and/or cytokine(s) that is (are) pivotal to protection from disease, which are delivered to lung by nanoparticle carriers, and (2) the Adenovirus and Adeno-associated virus vectors for the expression of antigens and therapeutic genes. Thus, a number of genes, including IFN-alpha, IL-12, TNF-alpha, IP-10, Lymphotactin, MIP-1beta, CD40 etc have been cloned and expressed using adenoviral gene transfer systems. Depending upon the cancer model utilized, the functional studies include immune modulation, signal transduction and apoptosis.

Specifically in relation to lung cancer, our current research focuses on the anti-cancer role of certain cytokines and chemokines on a number of tumorigenic cell lines and melanoma cell line B16, in vitro and in mouse models in vivo. Thus, recombinant Adenoviruses expressing IFN-gamma or 2'-5'oligoadenylate synthetase isoform-p-69 have been used to investigate the apoptosis of these cancer cells and the mechanism underlying apoptosis.

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This search will be conducted at the US National Library of Medicine (NLM) and PubMed.

Selected Publications
1. Matsuse H., Behera A, Kumar M, Rabb H, Lockey R, Mohapatra S.S. Recurrent respiratory syncytial virus infection in allergen-sensitized mice leads to persistent airway inflammation and airway hyperresponsiveness. Journal of Immunology. 164:6583-92, 2000.

2. Behera, A., Matsuse H., Kumar M., Kong X., Lockey R.F. and Mohapatra S.S. Blocking Intercellular Adhesion Modecule-1 on Human Epithelial Cells Decreases Respiratory Syncytial Virus Infection.
Biochem Biophys Res Commun 280:188-195, 2001.

3. Lockey RF and Mohapatra SS [The Amerian Lung Association Asthma Clinical Research Centers]. The safety of inactivated influenza vaccine in adults and children with asthma. The New England Journal of Medicine. 345:1529, 2001.

4. Kumar M., Behera A. K, Lockey, R.F. and Mohapatra, S.S. IFN-g and IL-12 plasmid DNAs as vaccine adjuvants in a murine model of grass allergy.
J Allergy Clin Immunol 108:402, 2001.

5. Mohapatra S.S. Gene transfer and transcription factors. Meetings Report. American Academy of allergy, Asthma and Immunology, New York, 2002, Invest Ddrugs, 5:312-315, 2002.

6. Behera AK, Kumar M, Lockey RF, Mohapatra SS. 2'-5' Oligoadenylate synthetase plays a critical role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells. J Biol Chem 277:25601-8, 2002.

7. Hellermann GR, Nagy SB, Kong X, Lockey RF, Mohapatra SS. Mechanism of Cigarette Smoke Condensate-induced Acute Inflammatory Response in Human Bronchial Epithelial cells. Resp. Res. 3:22-30, 2002.

8. Kumar, M, Behera AK, Lockey RF, Zhang J, Perez de la Cruz C, Chen l, Leong KW, Huang S-K and Mohapatra SS. Intranasal Gene transfer by Chitosan-DNA Nanospheres Protects BALB\C Mice Against Acute Respiratory Syncytial Virus Infection. Human Gene Therapy. 13:000-000, 2002.

9. Behera A, Kumar M, Lockey F, Mohapatra SS. Adenovirus mediated IFN-g gene therapy for allergic asthma: involvement of IL-12 and Stat-4 Signaling. Human Gene Therapy. In Press 2002.