Gadiparthi N. Rao, Ph.D.
Distinguished Professor
Voice: 1-901-448-7321
Fax: 1-901-448-7126
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Education

1973 B.Sc., Andhra University, Waltair, India.
1976 M.Sc., Gujarat University, Ahmedebad, India.
1979 Ph.D., Gujarat University, Ahmedebad, India.

Research Interest

Atherosclerosis and restenosis after angioplasty are the major cardiovascular problems particularly in western countries. Increased arterial smooth muscle cell growth and accumulation of extracellular matrix proteins are associated with the development of these vascular lesions. We believe that a change in the redox state of the arterial wall triggers these pathological events. Therefore, the major interest of our laboratory is to study the regulation and signal transduction mechanisms of redox-sensitive gene expression in vessel wall cells and investigate their role in atherosclerosis and neointima formation using animal models. The major techniques used in the laboratory are rat carotid artery injury, hind-limb ischemia, oxygen-induced retinopathy, Northern blot analysis, Western blot analysis, nuclear run-on assay, electrophoretic mobility shift assay, 2-D gel electrophoresis, high performance liquid chromatography, tube formation assay, cell migration assay, tissue culture, transfections, immunohistochemistry, Matrigel plug angiogenesis, chromatin immunoprecipitation assay, RT-PCR/QRT-PCR, molecular cloning, endothelial cell barrier function and microscopy.

Research Support

NIH RO1HL064165 (PI: G. N. Rao), "Eicosanoids and vascular wall remodeling", 2012-2017, $1,250,000
NIH RO1HL074860 (PI: G. N. Rao), "Eicosanoids and endothelial cell dysfunction", 2012-2016, $1,000,000
NIH RO1EY014856 (PI: G. N. Rao), "Mechanisms of retinal angiogenesis", 2012-2016, $1,000,000
NIH RO1HL069908 (PI: G.N. Rao), "NFATs and vascular injury", 2011-2016, $1,250,000
NIH RO1HL1037575 (PI: G.N. Rao), "GPCR signaling and vascular wall remodeling", 2011-2016, $1,650,000

Selected Publications

  1. Ghosh, S.K., Gadiparthi, L., Zeng, Z.Z., Bhanoori, M., Tellez, C., Bar-Eli, M. and Rao, G.N. ATF-1 mediates protease activated receptor-1 (PAR-1) but not receptor tyrosine kinase-induced DNA synthesis in vascular smooth muscle cells. J. Biol. Chem. 277, 21325-21331, 2002.
  2. Yellaturu, C.R., Bhanoori, M. Neeli, I. and Rao, G.N. N-Ethylmaleimide inhibits platelet-derived growth factor BB-stimulated Akt phosphorylation via activation of protein phosphatase 2A. J. Biol. Chem. 277, 40148-40155, 2002.
  3.  Zeng, Z.Z., Yellaturu, C.R., Neeli, I. and Rao, G.N. 5(S)-Hydroxyeicosatetraenoic acid stimulates DNA synthesis in human microvascular endothelial cells via activation of Jak/STAT and PI3-kinase/Akt signaling leading to induction of expression of basic fibroblast growth factor-2. J. Biol. Chem. 277, 41213-41219, 2002.
  4.  Yellaturu, C.R., Ghosh, S.K., Rao, R.K., Jennings, L.K., Hassid, A. and Rao, G.N. A potential role for nuclear factor of activated T cells in receptor tyrosine kinase and G protein-coupled receptor agonist-induced cell proliferation. Biochem J. 368, 183-190, 2002.
  5. Bhanoori, M., Yellaturu, C.R., Ghosh, S.K., Hassid, A., Jennings, L.K. and Rao, G.N. Thiol alkylation inhibits the mitogenic effects of platelet-derived growth factor and renders it proapoptotic via activation of STATs and p53 and induction of expression of caspase1 and p21waf1/cip1. Oncogene 22, 117-130, 2003.
  6. Yellaturu, C.R. and Rao, G.N. Cytosolic phospholipase A2 is an effector of Janus-activated kinase/Signal Transducers and Activators of Transcription signaling and is involved in platelet-derived growth factor BB-induced growth in vascular smooth muscle cells. J. Biol. Chem. 278, 9986-9992, 2003.
  7. Yellaturu, C.R. and Rao, G.N. A requirement for calcium-independent  phospholipase A2 in thrombin-induced arachidonic acid release and growth in vascular smooth muscle cells.  J. Biol. Chem.  278, 43831-43837, 2003.
  8. Neeli, I., Yellaturu, C. R. and Rao, G. N. Arachidonic acid activates translation initiation signaling in vascular smooth muscle cells. Biochem. Biophys. Res. Commun.  309, 755-761, 2003.
  9. Liu, Z., Dronadula, N. and Rao, G. N. A novel role for nuclear factor of activated T cells in receptor tyrosine kinase and G protein-coupled receptor agonist-induced vascular smooth muscle cell motility.  J. Biol. Chem. 279, 41218-41226, 2004.
  10. Neeli, I., Liu, Z., Dronadula, N., Ma, Z. A. and Rao, G. N. An essential role of Jak-2/STAT-3/cPLA2 axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility.  J. Biol. Chem. 279, 46122-46128, 2004.
  11. Dronadula, N., Liu, Z., Wang, C., Cao, H. and Rao, G. N. STAT-3-dependent expression of cPLA2 is required for thrombin-induced vascular smooth muscle cell motility.  J. Biol. Chem. 280, 3112-3120, 2005.
  12. Liu, Z., Zhang, C., Dronadula, N., Li, Q. and Rao, G. N. Blockade of nuclear factor of activated T cells activation signaling suppresses balloon injury-induced neointima formation in a rat carotid artery model. J. Biol. Chem. 280, 14700-14708, 2005.
  13. Zhang, B. Cao, H. and Rao, G. N. 15(S)-Hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K-Akt-mTOR-S6K1 signaling.  Cancer  Res. 65, 7283-7291, 2005.
  14. Cao, H., Dronadula, N. and Rao, G. N. Thrombin induces the expression of FGF-2 via activation of PI3K-Akt-Fra-1 signaling axis leading to DNA synthesis and motility in vascular smooth muscle cells. Am. J. Physiol. 290, C172-C182, 2006.
  15. Zhang, B., Cao, H. and Rao, G. N. Fibroblast growth factor-2 is a downstream mediator of PI3K-Akt signaling in 14, 15-epoxyeicosatrienoic acid-induced angiogenesis.  J. Biol. Chem. 281, 905-914, 2006 .
  16. Dronadula, N., Blaskova, E., Li, Q., Rizvi, F. and Rao, G. N. Involvement of cAMP response element-binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility. J. Lipid Res. 47, 774-784, 2006.
  17. Cao, H., Dronadula, N., Rizvi, F., Li, Q. Srivastava, K. Gerthoffer, W. T. and Rao, G. N. Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis facilitating thrombin-induced vascular smooth muscle cell growth and motility. Circ. Res. 98, 913-922, 2006.
  18. Wang, D., Liu, Z., Li, Q., Karpurapu, M., Kundumani-Sridharan, V., Cao, H., Dronadula, N., Rizvi, F., Bajpai, A.K., Zhang, C., Muller-Newen, G., Harris, K.W. and Rao, G.N. An essential role for gp130 in neointima formation following balloon injury. Circ Res. 100, 807-816 2007.
  19. Srivastava, K., Kundumani-Sridharan, V., Zhang, B., Bajpai, A.K. and Rao, G.N. 15(S)-Hydroxyeicosatetraenoic acid-induced angiogenesis requires signal transducer and activator of transcription-3-dependent expression of vascular endothelial growth factor.  Cancer  Res. 67, 4328-4336, 2007.
  20. Kundamani-Sridharan, V., Wang, D., Liu, Z., Zhang, C., Dronadula, N. and Rao, G. N. Activation of signal transducer and activator of transcription-5B in the vessel wall by balloon injury leads to cyclin D1 upregulation and neointima formation. Am J. Pathol. 171:1381-1394, 2007.
  21. Bajpai, A. K., Blaskova, E., Pakala, S.  B., Zhao, T., Glasgow, W. C., Penn, J. S., Johnson, D. A., Rao, G. N. 15(S)-HETE production in human retinal microvascular endothelial cells by hypoxia: Novel role for MEK1 in 15(S)-HETE induced angiogenesis. Invest Ophthalmol Vis Sci. 48, 4930-4938, 2007.
  22. Cheranov, S.Y., Karpurapu, M., Wang, D., Zhang, B., Venema R. C. and Rao, G.N. An essential role for Src-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis. Blood. 111, 5581-5591, 2008
  23. Karpurapu, M., Wang, D. Singh, N. K., Li, Q. and Rao, G. N. NFATc1 targets cyclin A in the regulation of vascular smooth muscle cell multiplication during restenosis. J. Biol. Chem. 283, 26577-26590, 2008.
  24. Zhao, T., Wang, D., Cheranov, S.Y., Karpurapu, M., Chava, K. R., Kundumani-Sridharan, V., Johnson, D. A, Penn, J. S., and Rao, G. N. A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis. J. Lipid Res. 50, 521-533, 2009.
  25. Chava, K. R., Karpurapu, K., Wang, D., Bhanoori, M., Kundumani-Sridharan, V., Zhang, Q., Ichiki, T., Glasgow, W. C., and Rao, G. N. CREB-mediated IL-6 expression is required for 15(S)-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration. ATVB. 29, 809-815, 2009.
  26. Cheranov, S. Y., Wang, D., Kundumani-Sridharan, V., Karpurapu, M., Zhang, Q., Chava, K. R., and Rao, G. N. 15(S)-hydroxyeicosatetraenoi acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B-dependent expression of interleukin-8. Blood. 113, 6023-6033, 2009.
  27. Wang, D., Paria, B. C., Zhang, Q., Karpurapu, M., Li, Q., Gerthoffer, W. T., Nakaoka, Y., and Rao, G. N. A role for gab1/shp2 in thrombin activation of pak1: gene transfer of kinase-dead pak1 inhibits injury-induced restenosis. Circ. Res. 104, 1066-1075, 2009.
  28. Potula, H. S. K., Wang, D., Karpurapu, M., Kundumani-Sridharan, V., Quyen, D. V., Singh, N. K., Park, E. A., Glasgow, W. C., and Rao, G. N.  Src-dependent STAT-3-mediated expression of monocyte chemoattractant protein-1 is required for 15(S)-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration. J. Biol. Chem. 284, 31142-31155, 2009.
  29. Karpurapu, M., Wang, D., Quyen, D. V., Kim T. K., Kundumani-Sridharan, V., Pulusani, S. and Rao, G. N. Cyclin D1 is a bona fide target gene of NFATc1 and is sufficient in the mediation of injury-induced vascular wall remodeling. J. Biol. Chem. 285, 3510-3523, 2009.
  30. Kundumani-Sridharan, V., Niu, J., Wang, D., Quyen, D. V., Zhang, Q., Singh, N. K., Subramani, J., Karri, S. and Rao, G. N. 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Src-mediated Egr-1-dependent rapid induction of FGF-2 expression. Blood. 115,  2105-2116, 2009.
  31. Singh, N. K., Quyen, D. V., Kundumani-Sridharan, V., Brooks, P. C. and Rao G. N. AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis. J. Biol. Chem. 285, 16830-16843, 2010.
  32. Qiuhua Zhang, Q., Wang, D., Kundumani-Sridharan, V., Gadiparthi, L., Johnson, D. A., Tigyi, G. J. and Rao, G. N. PLD1-dependent PKCgamma activation downstream to Src is essential for the development of pathological retinal neovascularization. Blood. 116, 1377-1385, 2010.
  33. Singh, N. K., Wang, D., Quyen, D. V., Niu, J., Kundumani-Sridharan, V. and Rao, G. N. 15-Lipoxygenase 1-enhanced Src-Janus kinase 2-signal transducer and activator of transcription 3 stimulation and monocyte chemoattractant protein-1 expression require redox-sensitive activation of epidermal growth factor receptor in vascular wall remodeling. J. Biol. Chem. 286, 22478-22488, 2011.
  34. Zhang, Q., Wang, D., Kundumani-Sridharan, V., Gadiparthi, L., Singh, N. K. and Rao, G. N. Activation of cytosolic phospholipase A2 downstream to Src-PLD1-PKCgamma signaling axis is required for hypoxia-induced pathological retinal angiogenesis. J. Biol. Chem. 286, 22489-22498, 2011.
  35. Singh, N. K., Kundumani-Sridharan, V. and Rao, G. N. 12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation. Blood. 118, 5701-5712, 2011.
  36. Kundumani-Sridharan, V., Van Quyen, D., Subramani, J., Singh, N. K., Chin, Y. E. and Rao, G. N. Novel interactions between NFATc1 (Nuclear Factor of Activated T cells c1) and STAT-3 (Signal Transducer and Activator of Transcription-3) mediate G protein-coupled receptor agonist, thrombin-induced biphasic expression of cyclin D1, with first phase influencing cell migration and second phase directing cell proliferation. J. Biol. Chem. 287, 22463-22482, 2012.
  37. Singh, N. K., Kundumani-Sridharan, V., Kumar, S., Verma, S. K., Kotla, S., Mukai, H., Heckle, M. R. and Rao, G. N. Protein kinase N1 is a novel substrate of NFATc1-mediated cyclin D1-CDK6 activity and modulates vascular smooth muscle cell division and migration leading to inward blood vessel wall remodeling. J. Biol. Chem. 287, 36291-36304, 2012.
  38. Gadepalli, R., Singh, N. K., Kundumani-Sridharan, V., Heckle, M. R. and Rao, G. N. Novel role of proline-rich nonreceptor tyrosine kinase 2 in vascular wall remodeling after balloon injury. ATVB. 32, 2652-2661, 2012.
  39. Singh, N. K., Hansen, D. E. 3rd., Kundumani-Sridharan, V. and Rao, G. N. Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKC?-cPLA2 activation and retinal neovascularization. Blood. 2013 Jan 14. [Epub ahead of print].

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