Sekhar R. Konjeti, Ph.D.

Research Professor

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Faculty Appointments
Research Professor of Radiation Oncology
Ph.D., Organic Chemistry, Gulbarga University, Karnataka, IndiaM.Sc., Chemistry, Mangalore University, Mangalore, IndiaB.S., Chemistry, Physics, Maths, Andhra University, Visakhapatnam, India
Office Address
E1200 Medical Center North
Dept. Radiation Oncology
1161 21st avenue south
Nashville, TN 37232
Research Description
Research Keywords
Glutathione, Oxidative Stress, GCS, Chemoprevention, Nrf2, Keap1, Antioxidants, Radiosensitizers, Angiogenesis Inhibitors, Drug discovery, Indoles
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 [print-electronic]. 2013 Jun; 31(3): 535-44. PMID: 23054211, PMCID: PMC3553230, DOI: 10.1007/s10637-012-9884-9, ISSN: 1573-0646.

Sekhar KR, Reddy YT, Reddy PN, Crooks PA, Venkateswaran A, McDonald WH, Geng L, Sasi S, Van Der Waal RP, Roti JL, Salleng KJ, Rachakonda G, Freeman ML. The novel chemical entity YTR107 inhibits recruitment of nucleophosmin to sites of DNA damage, suppressing repair of DNA double-strand breaks and enhancing radiosensitization. Clin. Cancer Res [print-electronic]. 2011 Oct 10/15/2011; 17(20): 6490-9. PMID: 21878537, PMCID: PMC3195947, PII: 1078-0432.CCR-11-1054, DOI: 10.1158/1078-0432.CCR-11-1054, ISSN: 1078-0432.

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 [print-electronic]. 2011 Sep 9/15/2011; 51(6): 1175-83. PMID: 21712086, PMCID: PMC3156301, PII: S0891-5849(11)00354-6, DOI: 10.1016/j.freeradbiomed.2011.05.038, ISSN: 1873-4596.

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 [print-electronic]. 2011 Aug 8/1/2011; 51(3): 619-25. PMID: 21605664, PMCID: PMC3129370, PII: S0891-5849(11)00285-1, DOI: 10.1016/j.freeradbiomed.2011.04.044, ISSN: 1873-4596.

Francis SH, Sekhar KR, Ke H, Corbin JD. Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds. Handb Exp Pharmacol. 2011; (200): 93-133. PMID: 20859794, DOI: 10.1007/978-3-642-13443-2_4, ISSN: 0171-2004.

Venkateswaran A, Reddy YT, Sonar VN, Muthusamy V, Crooks PA, Freeman ML, Sekhar KR. Antiangiogenic properties of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol/one analogs and their derivatives. Bioorg. Med. Chem. Lett [print-electronic]. 2010 Dec 12/15/2010; 20(24): 7323-6. PMID: 21055930, PMCID: PMC3001633, PII: S0960-894X(10)01521-0, DOI: 10.1016/j.bmcl.2010.10.060, ISSN: 1464-3405.

Pruitt R, Sasi N, Freeman ML, Sekhar KR. Radiosensitization of cancer cells by hydroxychalcones. Bioorg. Med. Chem. Lett [print-electronic]. 2010 Oct 10/15/2010; 20(20): 5997-6000. PMID: 20826087, PMCID: PMC2946792, PII: S0960-894X(10)01217-5, DOI: 10.1016/j.bmcl.2010.08.081, ISSN: 1464-3405.

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 [print-electronic]. 2010 Jun 6/24/2010; 29(25): 3703-14. PMID: 20440267, PMCID: PMC2892014, PII: onc2010118, DOI: 10.1038/onc.2010.118, ISSN: 1476-5594.

Sekhar KR, Rachakonda G, Freeman ML. Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicol. Appl. Pharmacol [print-electronic]. 2010 Apr 4/1/2010; 244(1): 21-6. PMID: 19560482, PMCID: PMC2837771, PII: S0041-008X(09)00265-8, DOI: 10.1016/j.taap.2009.06.016, ISSN: 1096-0333.

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 [print-electronic]. 2010 Jan 1/15/2010; 20(2): 600-2. PMID: 20005706, PMCID: PMC4159675, PII: S0960-894X(09)01652-7, DOI: 10.1016/j.bmcl.2009.11.082, ISSN: 1464-3405.

Geng L, Rachakonda G, Morré DJ, Morré 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 [print-electronic]. 2009 Sep; 23(9): 2986-95. PMID: 19395476, PMCID: PMC2796904, PII: fj.09-130005, DOI: 10.1096/fj.09-130005, ISSN: 1530-6860.

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 [print-electronic]. 2008 Mar; 21(3): 705-10. PMID: 18251510, DOI: 10.1021/tx700302s, ISSN: 0893-228X.

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. 2008 Jan 1/15/2008; 68(2): 364-8. PMID: 18199529, PII: 68/2/364, DOI: 10.1158/0008-5472.CAN-07-2170, ISSN: 1538-7445.

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 [print-electronic]. 2007 Dec 12/15/2007; 17(24): 6821-4. PMID: 17980582, PMCID: PMC3726020, PII: S0960-894X(07)01204-8, DOI: 10.1016/j.bmcl.2007.10.035, ISSN: 1464-3405.

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 [print-electronic]. 2007 Jan 1/26/2007; 282(4): 2529-37. PMID: 17127771, PII: M607622200, DOI: 10.1074/jbc.M607622200, ISSN: 0021-9258.

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. 2007 Jan 1/15/2007; 67(2): 695-701. PMID: 17234780, PII: 67/2/695, DOI: 10.1158/0008-5472.CAN-06-3212, ISSN: 0008-5472.

Geng L, Cuneo KC, Cooper MK, Wang H, Sekhar K, Fu A, Hallahan DE. Hedgehog signaling in the murine melanoma microenvironment. Angiogenesis [print-electronic]. 2007; 10(4): 259-67. PMID: 17762973, DOI: 10.1007/s10456-007-9078-9, ISSN: 0969-6970.

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. 2006 Nov; 5(11): 2659-65. PMID: 17121912, PII: 5/11/2659, DOI: 10.1158/1535-7163.MCT-06-0261, ISSN: 1535-7163.

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. 2006 Oct 10/15/2006; 66(20): 10040-7. PMID: 17047067, PII: 66/20/10040, DOI: 10.1158/0008-5472.CAN-06-0802, ISSN: 0008-5472.

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. 2006 Sep; 28(9): 813-8. PMID: 16637057, DOI: 10.1002/hed.20430, ISSN: 1043-3074.

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. 2005 Nov 11/15/2005; 63(4): 1228-36. PMID: 16253777, PII: S0360-3016(05)02143-7, DOI: 10.1016/j.ijrobp.2005.07.956, ISSN: 0360-3016.

Hong F, Sekhar KR, Freeman ML, Liebler DC. Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J. Biol. Chem [print-electronic]. 2005 Sep 9/9/2005; 280(36): 31768-75. PMID: 15985429, PII: M503346200, DOI: 10.1074/jbc.M503346200, ISSN: 0021-9258.

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. 2005 Feb 2/1/2005; 38(3): 375-87. PMID: 15629866, PII: S0891-5849(04)00882-2, DOI: 10.1016/j.freeradbiomed.2004.10.033, ISSN: 0891-5849.

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. 2005; 307: 239-62. PMID: 15988068, PII: 1-59259-839-0:239, DOI: 10.1385/1-59259-839-0:239, ISSN: 1064-3745.

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. 2005 Jan; 17(1): 5-9. PMID: 15538396, PII: 3901283, DOI: 10.1038/sj.ijir.3901283, ISSN: 0955-9930.

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. 2004 Oct 10/19/2004; 99(3): 369-81. PMID: 15451595, PII: S0168-3659(04)00348-7, DOI: 10.1016/j.jconrel.2004.07.024, ISSN: 0168-3659.

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. 2004 Jul; 66(1): 144-52. PMID: 15213306, PII: 66/1/144, DOI: 10.1124/mol.66.1.144, ISSN: 0026-895X.

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. 2003 Oct 10/15/2003; 63(20): 6920-7. PMID: 14583492, ISSN: 0008-5472.

Francis SH, Sekhar KR, Rouse AB, Grimes KA, Corbin JD. Single step isolation of sildenafil from commercially available Viagra tablets. Int. J. Impot. Res. 2003 Oct; 15(5): 369-72. PMID: 14562139, PII: 3901040, DOI: 10.1038/sj.ijir.3901040, ISSN: 0955-9930.

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. 2003 Sep 9/1/2003; 63(17): 5636-45. PMID: 14500406, ISSN: 0008-5472.

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

Sekhar KR, Yan XX, Freeman ML. Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2. Oncogene. 2002 Oct 10/3/2002; 21(44): 6829-34. PMID: 12360409, DOI: 10.1038/sj.onc.1205905, ISSN: 0950-9232.

Sekhar KR, Spitz DR, Harris S, Nguyen TT, Meredith MJ, Holt JT, Gius D, Marnett LJ, Summar ML, Freeman ML. Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase. Free Radic. Biol. Med. 2002 Apr 4/1/2002; 32(7): 650-62. PMID: 11909699, PII: S0891584902007554, ISSN: 0891-5849.

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. 2000 Apr 4/2/2000; 270(1): 311-7. PMID: 10733945, PII: S0006-291X(00)92419-7, DOI: 10.1006/bbrc.2000.2419, ISSN: 0006-291X.

Soltaninassab SR, Sekhar KR, Meredith MJ, Freeman ML. Multi-faceted regulation of gamma-glutamylcysteine synthetase. J. Cell. Physiol. 2000 Feb; 182(2): 163-70. PMID: 10623879, PII: 10.1002/(SICI)1097-4652(200002)182:2<163::AID-JCP4>3.0.CO;2-1, DOI: 10.1002/(SICI)1097-4652(200002)182:2<163::AID-JCP4>3.0.CO;2-1, ISSN: 0021-9541.

Sekhar KR, Freeman ML. Autophosphorylation inhibits the activity of gamma-glutamylcysteine synthetase. J. Enzym. Inhib. 1999; 14(4): 323-30. PMID: 10445052, ISSN: 8755-5093.

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. 1998 Jul 7/30/1998; 248(3): 458-63. PMID: 9703946, PII: S0006-291X(98)98998-7, DOI: 10.1006/bbrc.1998.8998, ISSN: 0006-291X.

Sekhar KR, Freeman ML. PEST sequences in proteins involved in cyclic nucleotide signalling pathways. J. Recept. Signal Transduct. Res. 1998 Mar; 18(2-3): 113-32. PMID: 9651881, DOI: 10.3109/10799899809047740, ISSN: 1079-9893.

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. 1998; 29(1-2): 145-57. PMID: 9631243, DOI: 10.1007/BF02737833, ISSN: 1085-9195.

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. 1997 Sep 9/9/1997; 36(36): 11002-11. PMID: 9283092, PII: bi9711590, DOI: 10.1021/bi9711590, ISSN: 0006-2960.

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. 1997 May 5/29/1997; 234(3): 588-93. PMID: 9175757, PII: S0006-291X(97)96697-3, DOI: 10.1006/bbrc.1997.6697, ISSN: 0006-291X.

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. 1997 May; 147(5): 592-7. PMID: 9146705, ISSN: 0033-7587.

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. 1997 May; 171(2): 143-51. PMID: 9130461, PII: 10.1002/(SICI)1097-4652(199705)171:2<143::AID-JCP4>3.0.CO;2-O, DOI: 10.1002/(SICI)1097-4652(199705)171:2<143::AID-JCP4>3.0.CO;2-O, ISSN: 0021-9541.

Sekhar KR, Grondin P, Francis SH and Corbin JD. Phosphodiesterase Inhibitors. [place unknown: publisher unknown]; 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. 1993; 43: 27-33. PMID: 8396316, ISSN: 0379-0363.

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. 1992 Jul; 42(1): 103-8. PMID: 1321950, ISSN: 0026-895X.

Hiremath SP, Sonar VN, Sekhar KR and Purohit MG. Synthesis of Oxadiazolyl , Thiadiazolyl and Triazolylindoles and Indolylthiazolidinones. Indian J. Chem. 1989; 28B: 626-30.

Hiremath SP, Ashok U, Sekhar KR, and Purohit MG. Synthesis of Various Pyrazole-1-Carbonylindoles. Indian J. Chem. 1988; 27B: 758-62.

Hiremath SP, Sekhar KR, and Purohit MG. Synthesis of Indolylpyrimidinediones and Indolylthiazolidinones. Indian J. Chem. 1988; 27B: 678-80.

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: 1118-24.

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: 367-76.

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: 372-5.