Faculty and Staff Detail
|
Somanath Shenoy, Ph.D. Assistant Professor CET |
| Contact Information | |
|---|---|
| Phone: | (706) 721-4250 |
| Email: | sshenoy@mail.mcg.edu |
| Fax: | (706) 721-3994 |
| Office: | |
| Address: |
Medical College of Georgia UGA Clinical Pharmacy Program HM-1200 Augusta, GA 30912 |
| Biosketch | |||
|---|---|---|---|
| B.S. | Mahatma Gandhi University | India | 1994 |
| M.S. | Annamalai University | India | 1996 |
| Ph.D. | NDRI, Indian Council of Agricultural Research | India | 2000 |
| Postdoctoral Fellow | Biological Sciences, Kent State University | Kent, OH | 2002-2003 |
| Postdoctoral Fellow | Molecular Cardiology, Cleveland Clinic | Cleveland, OH | 2003-2007 |
| Research Associate | Center for Cellular and Molecular Biology | India | 2000-2001 |
| Lecturer/Instructor | Kurukshetra University | India | 2001-2002 |
| Research Associate | Molecular Cardiology, Cleveland Clinic | Cleveland, OH | 2007-2008 |
| Project Scientist | Molecular Cardiology, Cleveland Clinic | Cleveland, OH | 2008-2009 |
| Assistant Professor | University of Georgia | Augusta, GA | 2009-Present |
- Honors and Awards
- • Young Investigator Award (2008) at the 12th Biennial Midwest Platelet Conference, University of Kentucky, Lexington, KY.
• New Investigator Travel Award (2007) at the 4th Annual Symposium of the American Heart Association Council on Basic Cardiovascular Sciences, Keystone, CO.
• Junior Investigator Award of Excellence (2007) at the Lerner Research Institute staff research retreat, Cleveland Clinic, for the second consecutive year.
• Junior Investigator Award of Excellence (2006) at the Lerner Research Institute staff research retreat, Cleveland Clinic.
• Irvine H. Page Award (2005) for the best publication at the Department of Molecular Cardiology, Cleveland Clinic.
• Invention disclosure (patent) with Cleveland Clinic (2005) Novel approaches to control vascular maturation and permeability.
• Innovator Award (2005) by the Cleveland Clinic for the invention of “Novel approach to control vascular maturation and permeability”.
• Runner-up for the best student (M.S., 1996) by The Society of Biological Chemists (India), Annamalai University Chapter.
- Area of Expertise
- Many recent studies have revealed the importance of integrins as well as extracellular matrix proteins and their cross-talk with many growth factors, in the regulation of tumor angiogenesis and direct effects on tumor growth (Reviewed in Somanath et al, Cell Biochem. Biophys., 2009; Somanath et al, Angiogenesis, 2009). However, converting this basic information into translational medicine suffers a major setback due to many over compensatory or un-anticipated effects during various phases of clinical trials. PI3 kinase-Protein kinase B (Akt) signaling is activated downstream of growth factor stimulation as well as during interactions between integrins to its matrix ligands. Akt has been implicated to regulate multiple cellular processes both in vascular cells and cancer/tumor cells that include survival, cell cycle, transcription, translation, adhesion and migration on various matrix proteins as well as in the secretion of many pro- and anti- angiogenic and –tumorigenic agents (Somanath et al, Cell cycle, 2006). Compounds targeting Akt signaling is also under clinical trials. However, many of them suffer setbacks due to poor understanding of how Akt regulates a plethora of substrates. Computational analysis suggests many more substrates for Akt in mammalian cells, than that is known to us till date, thus indicating the necessary caution to be taken while targeting Akt for therapy. Our recent studies in endothelial cells and fibroblasts revealed that Akt is necessary for the regulation of integrin activation and extracellular matrix assembly (Somanath et al, J Biol Chem., 2007) involving many intracellular signaling molecules such as Rac1 and p21 activated kinase1 (Pak1) (Somanath et al, J Cell Physiol, 2009). Our recent study also indicate that Akt induces oncogenic transformation via activation of MAP kinases involving Rac1-p21 activated kinase1 (Pak1) signaling pathway (Somanath et al, Oncogene, 2009).
Although pro-angiogenic and pro-tumorigenic in function, a balance in Akt activity is necessary for the proper regulation of physiological and pathological angiogenesis in vivo (Chen & Somanath et al, Nature Medicine, 2005; Somanath et al, Angiogenesis, 2008). Our studies, for the first time, indicated that if not regulated properly, long term inactivation of Akt can have un-anticipated effects on its therapeutic applications. Recent efforts on targeting Akt and its signaling partners such as Rac, Pak and mTOR for anti-angiogenic therapy can be improved if one understands the complexity of Akt signaling in mammalian cells. In order to do that we put forward efforts to study the importance of each isoform of 3 gene Akt family using specific knockout mouse models. My lab is interested in understanding the molecular mechanisms by which Akt regulates vascular permeability, extracellular matrix remodling and angiogensis to various stimuli. In addition, we are interested in understanding the molecular mechanisms by which Akt coordinates angiogenesis and prostate cancer growth & metastasis.
- Representative Publications
- 1. Somanath, P.R., Vijai, J., Kichina, J.V., Byzova, T.V. and Kandel, E.S. 2009. The role of Pak-1 in activation of MAP kinase cascade and oncogenic transformation by Akt. Oncogene (In Press).
2. Somanath, P.R., Malinin, N.L and Byzova, T.V. 2009. Coperation between VEGFR-2 and integrin alphav beta3 in angiogenesis. Angiogenesis, (In Press).
3. Somanath, P.R. and Byzova, T.V. 2009. 14-3-3beta- Rac1 - p21 activated kinase signaling regulates Akt1 mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly. J Cell. Physiol., 218(2):394-404.
4. Somanath, P.R., Ciocea, A and Byzova, T.V. 2009. Integrin and growth factor receptor alliance in angiogenesis. Cell Biochem. Biophys., 53(2): 53-64.
5. Feng, W., McCabe, N.P., Mahabeleshwar, G.H., Somanath, P.R., Phillips, D.R. and Byzova, T.V. 2008. The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells. J Cell Biol., 183(6): 1145-1157.
6. Somanath, P.R., Chen, J., Byzova, T.V. 2008. Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing. Angiogenesis. Apr 16; 11 (3): 277-288.
7. Mahabeleshwar, G.H., Chen, J., Feng, W., Somanath, P.R., Razorenova, O.V., Byzova, T.V. 2008. Integrin affinity modulation in angiogenesis. Cell Cycle, 7(3):335-347.
8. Somanath, P.R., Kandel, E.S., Hay, N, Byzova, T.V. 2007. Akt1 signaling regulates integrin activation, matrix recognition and fibronectin matrix assembly. J. Biol. Chem., 282(31): 22964-22976.
9. Somanath, P.R, Razorenova, O.V., Chen, J., Byzova, T.V. 2006. Akt1 in endothelial cell and angiogenesis. Cell Cycle 5(5): 512-518.
10. Mahabeleshwar, G.H., Somanath PR, Byzova TV. 2006. Methods for isolation of endothelial and smooth muscle cells and in vitro proliferation assays. In: Cardiovascular disease: Methods and protocols. Methods in Molecular Medicine. 129:197-208. Cardiovascular Medicine, HUMANA Press, Totowa, NJ.
11. Chen, J. & Somanath, P.R (Co-first authors), Chen, WS, Hay, N, Byzova, T.V. 2005. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nature Med. 11 (11): 1188-1196.
12. Huang, Z., Somanath, P.R, Chakrabarti, R., Eddy, EM, Vijayaraghavan S. 2005. Changes in intracellular distribution and activity of protein phosphatase PP1gamma2 and its regulating proteins in spermatozoa lacking AKAP4. Biol. Reprod. 72(2): 384-392.
13. Somanath, P.R, Jack, S, Vijayaraghavan S. 2004. Changes in sperm glycogen synthase kinase-3 serine phosphorylation and activity accompany motility initiation and stimulation. J. Androl. 25(4): 605-617.
14. Somanath, P.R, and Gandhi, K.K. 2004. Isolation and partial characterization of the plasma and outer acrosomal membranes of goat spermatozoa. Small Rumin. Res. 53(1-2), 67-74.
15. Myers, K, Somanath, P.R, Berryman, M, Vijayaraghavan S. 2004. Identification of chloride intracellular channel proteins in spermatozoa. FEBS Lett. 566(1-3), 136–140.
16. Mishra, S, Somanath, P.R, Huang, Z, Vijayaraghavan S. 2003. Binding and inactivation of the germ cell specific protein phosphatase PP1gamma2 by Sds22 during epididymal sperm maturation. Biol. Reprod. 69(5), 1572–1579.
17. Somanath, P.R, and Gandhi, K.K. 2002. Expression of membrane associated non-genomic progesterone receptor(s) in caprine spermatozoa. Anim. Reprod. Sci. 74(3-4), 195-205.
18. Somanath, P.R, and Gandhi, K.K. 2002. Role of Ca2+ and Ca2+ channels in progesterone induced acrosome reaction in caprine spermatozoa. Asia-Aust. J. Anim. Sci. 15(7), 949-956.
19. Somanath, P.R, and Gandhi, K.K. 2001. Role of diacyl glycerol (DAG) in progesterone induced acrosome reaction in caprine spermatozoa. Asia-Aust. J. Anim.Sci. 15(8), 1092-1097.
20. Somanath, P.R, Suraj, K and Gandhi, K.K. 2000. Caprine sperm acrosome reaction: Promotion by progesterone and homologous zona pellucida. Small Rumin. Res. 37(3), 279 286.
- Other
- Current grant support -
Title: Molecular mechanisms regulating Akt1 stimulated integrin activation, extracellular matrix secretion and assembly
Agency: Scientist Development Grant, American Heart Association, National Affiliate
Role: Principal Investigator
Period: January1, 2008 to December 31, 2011.
Total Award: $308,000
Fellowships/Grants -
• Scientist Development Grant Award (January, 2008 – December, 2011) by American Heart Association, National Centre.
• Senior Research Fellowship (June, 1999–December, 2000) by the Council of Scientific and Industrial research (CSIR), New Delhi, India.
• Junior Research Fellowship (June, 1996-May, 1999) from NDRI (Indian Council of Agricultural Research), India.
Professional society affiliations -
• American Heart association (AHA) and American Stroke Association (ASA)
• North American Vascular Biology Organization (NAVBO)