Shetty, Sreerama, Ph.D.

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Contact: sreerama.shetty@uthct.edu

Research Interest:

• Regulation of Gene Expression.
• Tumor Metastasis and Fibrinolysis during lung injury and remodeling.

Current Projects:
Posttranscriptional regulatory mechanism of urokinase and its receptor expression. Mechanisms of urokinase-mediated cellular transformation and invasion.

Research Overview:

Disordered fibrin turnover has been implicated in the pathogenesis of a wide spectrum of lung diseases. The urokinase-urokinase receptor system has, in particular, been linked to altered fibrin clearence in the context of inflammation and repair as well as neoplasia in the lung parenchyma. Urokinase and its receptor govern the transformation of surrounding host tissues. The mechanisms involve regulation of their expression at the posttranscriptional level. We are studying how expression of components of fibrinolysis (urokinase, urokinase receptor and plasminogen activator inhibitors) and tumor suppressor proteins lead to cellular transformation and propagation of neoplasms in the lung.

Selected Papers and Abstracts:

• Bhandary YP, Velusamy T, Shetty P, Tsuruta Y, Bdeir K, Cines DB, Abraham E, Shetty S. (2008) Posttranscriptional Regulation of Urokinase Receptor Expression in Lipopolysaccharide induced acute lung injury. Am J Resp Crit Care Med (in press).
• Shetty P, Velusamy T, Bhandary YP, Liu MC, Shetty RS, Shetty S. (2008). Urokinase expression by tumor suppressor protein p53: a novel role in mRNA turnover. Am J Resp Cell Mol Biol, 39: 364-372.
• Velusamy T, Shetty P, Bhandary YP, Liu MC, Shetty S. (2008) Posttranscriptional regulation of urokinase receptor expression by heterogeneous nuclear ribonuclear protein C. Biochemistry. 2008 Jun 17;47(24):6508-17. Epub 2008 May 22.PMID: 18494499.
• Shetty S, Shetty P, Idell S, Velusamy T, Bhandary YP, Shetty RS. (2008) Regulation of plasminogen activator inhibitor-1 expression by tumor suppressor protein p53. J Biol Chem 283: 19570-19580.
• Shetty S, Padijnayayveetil J, Tucker T, Stankowski, D, Idell S. (2008) The Fibrinolytic System and the Regulation of Lung Epithelial Cell Proteolysis, Signaling and Cellular Viability. Am J Physiol Lung Cell Mol Physiol. 2008 Oct 3. [Epub ahead of print].
• Shetty S, Velusamy T, Idell S, Shetty P, Mazar AP, Bhandary YP, Shetty RS. (2007). Regulation of urokinase receptor expression by p53: novel role in stabilization of uPAR mRNA. Mol. Cell. Biol. 27:5607-5618.
• Shetty S, Velusamy T, Idell S, Tang H, Shetty PK. (2007) Regulation of Urokinase Receptor Expression by Protein Tyrosine Phosphatases. Am J Physiol: Lung Cell Mol Physiol 292: L414-L421.
• Shetty S, Rao GN, Cines DB, Bdeir K. (2006) Urokinase induces activation of STAT3 in lung epithelial cells. Am J Physiol: Lung Cell Mol Physiol 291:L772-780.
• Shetty S, Idell S. (2006) Fibrinolysis: Plasminogen activator and plasmin. Encyclopedia Resp. Med. 1: 205-210.
• Idell S, Shetty S. (2006) Thrombolytic therapy. Encyclopedia Resp. Med. 1:231-236.
• Shetty, S., Gyetko, M. and Mazar, A. (2005) Induction of p53 by urokinase in lung epithelial cells. J. Biol. Chem. 280(30):28133-41.
• Shetty S. (2005) Protein synthesis and urokinase mRNA metabolism. Mol. Cell. Bio. 271:13-22.
• Shetty S. (2005). Regulation of Urokinase Receptor mRNA Stability by hnRNP C in Lung Epithelial Cells. Mol. Cell. Bio. 272:107-118.
• Shetty S, Ganachari M, Liu MC, Azghani A. Muniyappa H, Idell S. (2005) Regulation of urokinase receptor expression by phosphoglycerate kinase is independent of its catalytic activity. Am J Physiol: Lung Cell Mol Physiol. 289(4):L591-8.