Shetty, Sreerama, Ph.D.
- Lung epithelial injury and lung remodeling.
- Regulation of Gene Expression.
Posttranscriptional regulatory mechanism of urokinase-type plasminogen activator (uPA), its receptor (uPAR) and major uPA inhibitor, plasmonogen activatior inhibitor-1 (PAI-1) expression during lung injury and remodeling.
Elucidate how changes major components of uPA-fibrinolytic system contribute alveolar epithelial injury and develop interventions
Disordered alveolar fibrin turnover has been implicated in the pathogenesis of a wide spectrum of lung diseases including acute lung injury, its severe clinical form (ARDS), COPD, lung fibrosis, inflammation, infection and sepsis. uPA, uPAR and PAI-1 have, in particular, been linked to altered fibrin clearance in the context of lung injury and remodeling. The mechanisms involve regulation of uPA, uPAR and PAI-1 expression at the posttranscriptional level by tumor suppressor protein, p53. We are studying how changes in the expression of uPA, uPAR, PAI-1 and p53 lead to alveolar epithelial cell injury and subsequent development of lung fibrosis. Further, develop interventions to target p53-mediated coordinate regulation of major components of uPA-fibrinolytic system during lung injury to protect the alveolar epithelium and prevent fibrotic repair.
Selected Papers and Abstracts:
- Bhandary YP, Shetty SK, Marudamuthu AS, Ji H, Fu J, Idell S, Boggaram, VB, Neuenschwander PF, Morris GB and Shetty S. (2013) Regulation of alveolar epithelial injury and lung remodeling by p53-mediated changes in urokinase and plasminogen activator inhibitor-1. Am J Pathol 183: 131-143.
- Shetty SK, Bhandary YP, Marudamuthu AS, Abernathy D, Velusamy T, Starcher BC, Shetty S. (2012) Regulation of airway and alveolar epithelial cell apoptosis by p53 induced plasminogen activator inhibitor-1. Am J Resp cell Mol Biol 47(4):474-483. PMID:22592924.
- Shetty SK, Marudamuthu AS, Abernathy D, Shetty RS, Shetty P, Idell S, Bhandary YP, Ji H, Liu MC and Shetty S (2012) Post-transcriptional regulation of urokinase expression by lung epithelial cells. Biochemistry 51:205-213. PMID:22166006.
- Bhandary YP, Shetty SK, Marudamuthu AS, Gyetko MR, Idell S, Kermani MG, Shetty RS, Starcher BC, Shetty S. (2012) Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system. Am J Physiology: Lung cellular Mol Physiol 302(5):L463-73. PMID: 22140072.
- Yasuda S, Yasuda T, Fu J, Shetty S, Idell S, Boggaram V, Sakakibara Y, Suiko M, Liu M (2011) Sulfation of chlorotyrosine and nitrotyrosine by human lung endothelial and epithelial cells: role of the human cytosolic SULT1A3. Toxicol Appl Pharmacol 251(2):104-9. PMID:21168432.
- Midde KK, Batchinsky AI, Cancio LC, Shetty S, Komissarov AA, Florova G, Walker III KP, Koenig K, Chroneos ZC, Allen T, Chung K, Dubick M, Idell S (2011) Wood Bark Smoke Induces Lung and Pleural Plasminogen Activator Inhibitor 1 and Stabilizes its mRNA in Porcine Lung Cells. Shock. 36(2):128-37. PMID:21478814.
- Shetty S, Bhandary YP, Shetty SK, Velusamy T, Shetty P, Bdeir K, Gyetko MR, Cines DB, Idell S, Neuenschwander PF, Ruppert C, Guenther A, Abraham E, Shetty RS (2011) Induction of tissue factor by urokinase in lung epithelial cells and in the lungs. Am J Resp Crit Care Med 181:1-12.
- Shetty P, Velusamy T, Liu M, Bhandary YP, Shetty S (2010) Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase. Mol Cell Biochem 335:235-247.
- Shetty S, Velusamy T, Shetty RS, Tucker T, Koenig K., Shetty P, Bhandary YP, Idell S. (2010) Post-transcriptional Regulation of Plasminogen Activator Inhibitor-1 Expression in Human Pleural Mesothelial Cells. Am J. Resp Cell Mol Biol 43:358-367.
- Bhandary YP, Velusamy T, Shetty P, Shetty RS, Idell S, Cines DB, Bdeir K., Abraham E, Tsuruta Y, and Shetty S. (2009) Post-transcriptional regulation of urokinase-type plasminogen activator receptor expression in lipopolysaccharide-induced acute lung injury. Am J Resp Crit Care Med 179: 288-298.
- Shetty S, Padijnayayveetil J, Tucker T, Stankowska 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 Dec;295(6):L967-75. doi: 10.1152/ajplung.90349.2008. Epub 2008 Oct 3.
- Shetty P, Velusamy T, Bhandary YP, Liu M, Shetty RS. Shetty S. (2008) Posttranscriptional Regulation of Urokinase Expression by Tumor Suppressor Protein p53: A Novel Role in uPA mRNA Turnover. Am J Resp Cell Mol Biol 39:364-372.
- Velusamy T, Shetty P, Liu M, Bhandary YP. Shetty S. (2008) Posttranscriptional regulation of urokinase receptor expression by heterogeneous nuclear ribonuclear protein C. Biochemistry 47 (24):6508–6517.
- Shetty S, Shetty P, Velusamy T, Idell S, Bhandary YP. Shetty, R.S. (2008) Induction of Plasminogen activator inhibitor-1 mRNA Stabilization by Tumor Suppressor Protein p53. J Biol Chem 283:19570-19580.
- Shetty S, John J. and Idell S. (2008) Pleural Fibrosis. Text book of pleural diseases. Light RW and Lee YCG EDs, Hodder and Arnold press. 9:101-112.
- Shetty S, Velusamy T, Shetty PK., Idell S, Mazar, AP, Bhandary YP, Shetty, RS. (2007) Regulation of Urokinase Receptor Expression by p53: A Novel Role in Stabilization of uPAR mRNA. Mol Cell Biol 27:5607-5618.