Biomedical Research Education & Training
Faculty Member

Konjeti, Sekhar R., Ph.D.
Research Professor of Radiation Oncology

Lab Url: http://www.mc.vanderbilt.edu/radiationoncology/

Phone Number: 615-322-3603

Email Address: raja.konjeti@vanderbilt.edu

Konjeti, Sekhar's picture
Academic history
B.S., Andhra University, India
M.Sc., Mangalore University, India
Ph.D., Gulbarga University, India

Office Address   Mailing Address

E1200 MCN, 1161 21st Avenue S., Nashville, TN 37232

E1200 Medical Center North Dept. Radiation Oncology 37232


Research Keywords
Glutathione, Oxidative Stress, GCS, Chemoprevention, Nrf2, Keap1, Antioxidants, Radiosensitizers, Angiogenesis Inhibitors, Drug discovery, Indoles,Cancer,Enzyme action,Transcription factor

Research Description

Publications
Venkateswaran, A, Friedman, DB, Walsh, AJ, Skala, MC, Sasi, S, Rachakonda, G, Crooks, PA, Freeman, ML, Sekhar, KR. The novel antiangiogenic VJ115 inhibits the NADH oxidase ENOX1 and cytoskeleton-remodeling proteins. Invest New Drugs, 2012

Francis, SH, Sekhar, KR, Ke, H, Corbin, JD. Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds. Handb Exp Pharmacol(200), 93-133, 2011

Mukhopadhyay, S, Sekhar, KR, Hale, AB, Channon, KM, Farrugia, G, Freeman, ML, Gangula, PR. Loss of NRF2 impairs gastric nitrergic stimulation and function. Free Radic Biol Med, 51(3), 619-25, 2011

Sekhar, KR, Reddy, T, Reddy, N, Crooks, PA, Venkateswaran, A, McDonald, WH, Geng, L, Sasi, S, Van Der Waal, RP, Roti Roti, JL, Salleng, KJ, Rachakonda, G, Freeman, ML. The novel chemical entity YTR107 inhibits recruitment of nucleophosmin to the sites of DNA damage, suppressing repair of DNA double strand breaks, and enhancing radiosensitization. Clin Cancer Res, 2011

Travis, EL, Rachakonda, G, Zhou, X, Korhonen, K, Sekhar, KR, Biswas, S, Freeman, ML. NRF2 deficiency reduces life span of mice administered thoracic irradiation. Free Radic Biol Med, 51(6), 1175-83, 2011

Pruitt, R, Sasi, N, Freeman, ML, Sekhar, KR. Radiosensitization of cancer cells by hydroxychalcones. Bioorg Med Chem Lett, 2010

Rachakonda, G, Sekhar, KR, Jowhar, D, Samson, PC, Wikswo, JP, Beauchamp, RD, Datta, PK, Freeman, ML. Increased cell migration and plasticity in Nrf2-deficient cancer cell lines. Oncogene, 2010

Reddy, YT, Sekhar, KR, Sasi, N, Reddy, PN, Freeman, ML, Crooks, PA. Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents. Bioorg Med Chem Lett, 20(2), 600-2, 2010

Sekhar, KR, Rachakonda, G, Freeman, ML. Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicol Appl Pharmacol, 244(1), 21-26, 2010

Venkateswaran, A, Reddy, YT, Sonar, VN, Muthusamy, V, Crooks, PA, Freeman, ML, Sekhar, KR. Antiangiogenic properties of substituted (Z)-(A?)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol/one analogs and their derivatives. Bioorg Med Chem Lett, 20(24), 7323-6, 2010

Geng, L, Rachakonda, G, Morr??, DJ, Morr??, DM, Crooks, PA, Sonar, VN, Roti, JL, Rogers, BE, Greco, S, Ye, F, Salleng, KJ, Sasi, S, Freeman, ML, Sekhar, KR. Indolyl-quinuclidinols inhibit ENOX activity and endothelial cell morphogenesis while enhancing radiation-mediated control of tumor vasculature. FASEB J, 23(9), 2986-95, 2009

Brown, SL, Sekhar, KR, Rachakonda, G, Sasi, S, Freeman, ML. Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway. Cancer Res, 68(2), 364-8, 2008

Rachakonda, G, Xiong, Y, Sekhar, KR, Stamer, SL, Liebler, DC, Freeman, ML. Covalent Modification at Cys151 Dissociates the Electrophile Sensor Keap1 from the Ubiquitin Ligase CUL3. Chem Res Toxicol, 21(3), 705-710, 2008

Gao, L, Wang, J, Sekhar, KR, Yin, H, Yared, NF, Schneider, SN, Sasi, S, Dalton, TP, Anderson, ME, Chan, JY, Morrow, JD, Freeman, ML. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem, 282(4), 2529-37, 2007

Geng, L, Cuneo, KC, Cooper, MK, Wang, H, Sekhar, K, Fu, A, Hallahan, DE. Hedgehog signaling in the murine melanoma microenvironment. Angiogenesis, 10(4), 259-67, 2007

Sekhar, KR, Sonar, VN, Muthusamy, V, Sasi, S, Laszlo, A, Sawani, J, Horikoshi, N, Higashikubo, R, Bristow, RG, Borrelli, MJ, Crooks, PA, Lepock, JR, Roti Roti, JL, Freeman, ML. Novel chemical enhancers of heat shock increase thermal radiosensitization through a mitotic catastrophe pathway. Cancer Res, 67(2), 695-701, 2007

Sonar, VN, Thirupathi Reddy, Y, Sekhar, KR, Sasi, S, Freeman, ML, Crooks, PA. Novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(+/-)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents. Bioorg Med Chem Lett, 17(24), 6821-6824, 2007

Cao, C, Subhawong, T, Albert, JM, Kim, KW, Geng, L, Sekhar, KR, Gi, YJ, Lu, B. Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res, 66(20), 10040-7, 2006

Kim, KW, Mutter, RW, Cao, C, Albert, JM, Shinohara, ET, Sekhar, KR, Lu, B. Inhibition of signal transducer and activator of transcription 3 activity results in down-regulation of Survivin following irradiation. Mol Cancer Ther, 5(11), 2659-65, 2006

Stacy, DR, Ely, K, Massion, PP, Yarbrough, WG, Hallahan, DE, Sekhar, KR, Freeman, ML. Increased expression of nuclear factor E2 p45-related factor 2 (NRF2) in head and neck squamous cell carcinomas. Head Neck, 28(9), 813-8, 2006

Bakin, AV, Stourman, NV, Sekhar, KR, Rinehart, C, Yan, X, Meredith, MJ, Arteaga, CL, Freeman, ML. Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding Phase II detoxifying proteins. Free Radic Biol Med, 38(3), 375-87, 2005

Cao, C, Shinohara, ET, Li, H, Niermann, KJ, Kim, KW, Sekhar, KR, Gleave, M, Freeman, M, Lu, B. Clusterin as a therapeutic target for radiation sensitization in a lung cancer model. Int J Radiat Oncol Biol Phys, 63(4), 1228-36, 2005

Hong, F, Sekhar, KR, Freeman, ML, Liebler, DC. Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J Biol Chem, 280(36), 31768-75, 2005

Weeks, JL, Blount, MA, Beasley, A, Zoraghi, R, Thomas, MK, Sekhar, KR, Corbin, JD, Francis, SH. Radiolabeled ligand binding to the catalytic or allosteric sites of PDE5 and PDE11. Methods Mol Biol, 307, 239-62, 2005

Blount, MA, Beasley, A, Zoraghi, R, Sekhar, KR, Bessay, EP, Francis, SH, Corbin, JD. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol, 66(1), 144-52, 2004

Geng, L, Osusky, K, Konjeti, S, Fu, A, Hallahan, D. Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay. J Control Release, 99(3), 369-81, 2004

Weeks, JL, Zoraghi, R, Beasley, A, Sekhar, KR, Francis, SH, Corbin, JD. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. Int J Impot Res, 17(1), 5-9, 2004

Francis, SH, Sekhar, KR, Rouse, AB, Grimes, KA, Corbin, JD. Single step isolation of sildenafil from commercially available Viagra tablets. Int J Impot Res, 15(5), 369-72, 2003

Saha, D, Sekhar, KR, Cao, C, Morrow, JD, Choy, H, Freeman, ML. The antiangiogenic agent SU5416 down-regulates phorbol ester-mediated induction of cyclooxygenase 2 expression by inhibiting nicotinamide adenine dinucleotide phosphate oxidase activity. Cancer Res, 63(20), 6920-7, 2003

Sekhar KR, and Freeman ML. Regulation of Glutamate Cysteine Ligase. Recent Res. Devel. Biophys. Biochem, 3, 29-43, 2003

Sekhar, KR, Crooks, PA, Sonar, VN, Friedman, DB, Chan, JY, Meredith, MJ, Starnes, JH, Kelton, KR, Summar, SR, Sasi, S, Freeman, ML. NADPH oxidase activity is essential for Keap1/Nrf2-mediated induction of GCLC in response to 2-indol-3-yl-methylenequinuclidin-3-ols. Cancer Res, 63(17), 5636-45, 2003

Sekhar, KR, Spitz, DR, Harris, S, Nguyen, TT, Meredith, MJ, Holt, JT, Gius, D, Marnett, LJ, Summar, ML, Freeman, ML, Guis, D. Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase. Free Radic Biol Med, 32(7), 650-62, 2002

Sekhar, KR, Yan, XX, Freeman, ML. Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2. Oncogene, 21(44), 6829-34, 2002

Sekhar, KR, Soltaninassab, SR, Borrelli, MJ, Xu, ZQ, Meredith, MJ, Domann, FE, Freeman, ML. Inhibition of the 26S proteasome induces expression of GLCLC, the catalytic subunit for gamma-glutamylcysteine synthetase. Biochem Biophys Res Commun, 270(1), 311-7, 2000

Soltaninassab, SR, Sekhar, KR, Meredith, MJ, Freeman, ML. Multi-faceted regulation of gamma-glutamylcysteine synthetase. J Cell Physiol, 182(2), 163-70, 2000

Sekhar, KR, Freeman, ML. Autophosphorylation inhibits the activity of gamma-glutamylcysteine synthetase. J Enzyme Inhib, 14(4), 323-30, 1999

Corbin, JD, Beasley, A, Turko, IV, Haik, TL, Mangum, KA, Wells, JN, Francis, SH, Sekhar, KR. A photoaffinity probe covalently modifies the catalytic site of the cGMP-binding cGMP-specific phosphodiesterase (PDE-5). Cell Biochem Biophys, 29(1-2), 145-57, 1998

Meredith, MJ, Cusick, CL, Soltaninassab, S, Sekhar, KS, Lu, S, Freeman, ML. Expression of Bcl-2 increases intracellular glutathione by inhibiting methionine-dependent GSH efflux. Biochem Biophys Res Commun, 248(3), 458-63, 1998

Sekhar, KR, Freeman, ML. PEST sequences in proteins involved in cyclic nucleotide signalling pathways. J Recept Signal Transduct Res, 18(2-3), 113-32, 1998

McDuffee, AT, Senisterra, G, Huntley, S, Lepock, JR, Sekhar, KR, Meredith, MJ, Borrelli, MJ, Morrow, JD, Freeman, ML. Proteins containing non-native disulfide bonds generated by oxidative stress can act as signals for the induction of the heat shock response. J Cell Physiol, 171(2), 143-51, 1997

Sekhar, KR, Long, M, Long, J, Xu, ZQ, Summar, ML, Freeman, ML. Alteration of transcriptional and post-transcriptional expression of gamma-glutamylcysteine synthetase by diethyl maleate. Radiat Res, 147(5), 592-7, 1997

Sekhar, KR, Meredith, MJ, Kerr, LD, Soltaninassab, SR, Spitz, DR, Xu, ZQ, Freeman, ML. Expression of glutathione and gamma-glutamylcysteine synthetase mRNA is Jun dependent. Biochem Biophys Res Commun, 234(3), 588-93, 1997

Senisterra, GA, Huntley, SA, Escaravage, M, Sekhar, KR, Freeman, ML, Borrelli, M, Lepock, JR. Destabilization of the Ca2+-ATPase of sarcoplasmic reticulum by thiol-specific, heat shock inducers results in thermal denaturation at 37 degrees C. Biochemistry, 36(36), 11002-11, 1997

Sekhar KR, Grondin P, Francis SH and Corbin JD. Design and Synthesis of Xanthine and Cyclic GMP Analogs as Potent Inhibitors of PDE V and PDE I . Phosphodiesterase Inhibitors, 135-145, 1996

Corbin, JD, Woodall, CC, Colbran, JL, McAllister, LM, Sekhar, KR, Francis, SH. Identifying protein kinases in crude extracts that phosphorylate cyclic GMP-binding cyclic-GMP specific phosphodiesterase. Agents Actions Suppl, 43, 27-33, 1993

Sekhar, KR, Hatchett, RJ, Shabb, JB, Wolfe, L, Francis, SH, Wells, JN, Jastorff, B, Butt, E, Chakinala, MM, Corbin, JD. Relaxation of pig coronary arteries by new and potent cGMP analogs that selectively activate type I alpha, compared with type I beta, cGMP-dependent protein kinase. Mol Pharmacol, 42(1), 103-8, 1992

Hiremath SP, Sekhar KR, Sonar VN and Purohit MG. Synthesis of 1,2,4-Triazolo[3,4-f] 1,2,4-Triazino[3,4-a]Indoles . Indian J. Chem., 29B, 372-375, 1990.

Hiremath SP, Shivaramaiah K, Sekhar KR and Purohit MG. Synthesis of Substituted 2,5 bis(1,3,4-oxadiazolyl/Thiadiazolyl/1,2,4-Triazolyl)Indoles and Study of Their Biological Activities . Indian J. Chem, 29B, 1118-1124, 1990.

Hiremath SP, Sonar VN, Sekhar KR and Purohit MG. Synthesis of Substituted 5,6-Dihydroindolo[2,1-b][1,3]Diazepines, 1,2,3,4,5,6- Hexahydroindolo[3,2-b][1,4] Diazepin-5-Ones and 5,6,7,12- Tetrahydroindolo[3,2-b][1,5]Benzodiazepin-6-Ones . Proc. Natl. Acad. Sci., India, 60A, 367-376, 1990.

Hiremath SP, Sonar VN, Sekhar KR and Purohit MG. Synthesis of Oxadiazolyl , Thiadiazolyl and Triazolylindoles and Indolylthiazolidinones . Indian J. Chem, 28B, 626-630, 1989

Hiremath SP, Ashok U, Sekhar KR, and Purohit MG. Synthesis of Various Pyrazole-1-Carbonylindoles . Indian J. Chem, 27B, 758-762, 1988

Hiremath SP, Sekhar KR, and Purohit MG. Synthesis of Indolylpyrimidinediones and Indolylthiazolidinones . Indian J. Chem., 27B, 678-680, 1988


Postdoctoral Position Available
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Postdoctoral Position Details
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Updated Date
01/08/2013