Faculty & Staff Details
 |
Name: | Kalkunte Srivenugopal |
| Position: | Associate Professor | |
| Email: | Kalkunte.Srivenugopal@ttuhsc.edu | |
| Bio | Dr. Srivenugopal (Venu) joined the TTUHSC School of Pharmacy as an Associate Professor in September of 2002. He obtained his Ph.D. from the Indian Institute of Science in 1981 for pioneering work on polyamine enzymology in higher plants. As a Senior Fellow at the University of Washington, he continued work on polyamine-DNA interactions, and topoisomerases. He identified the DNA topoisomerase III (topo III) in E.coli during these studies. Dr. Venu later developed an interest in chemotherapy-induced DNA damage and its repair, which remains his current focus. Prior to his arrival at TTUHSC, Dr. Venu served on the faculty at the Chicago Medical School (now the Rosalind Franklin University of Medicine & Science), the University of Medicine & Dentistry of New Jersey (UMDNJ) and the University of Texas M.D. Anderson Cancer Center. His research on anticancer drug resistance focusing on the unique DNA repair protein MGMT (O6-methylguanine DNA methyltransferase) has been funded continuously since 1993 by agencies such as the American Cancer society, National Cancer Institute, and the Pediatric Brain Tumor Foundation. Ongoing research projects focus on p53 tumor suppressor, DNA replication/licensing, chemoprevention, and exploiting the posttranslational regulation of MGMT for enhanced anticancer therapies. Dr. Venu is widely sought for reviewing manuscripts submitted to various journals. |
Education:
B.S. (Honours), Botany, Zoology and Chemistry, Mysore University, India, 1973
M.S. Plant Biochemistry, Bangalore University, India, 1975
Ph.D. in Biochemistry, Thesis on " Enzymic and Regulatory Aspects of Polyamine Metabolism in Higher Plants" awarded by the Indian Institute of Science, Bangalore, India, 1981
Senior Fellow, Dept. of Biochemistry, University of Washington, Seattle, WA (10/1981-5/1987)
Senior Fellow, Dept. of Neurological Surgery, University of Washington, Seattle, WA (6/87-8/88)
Appointments:
10/1989-12/1990 Chief, Surgical Research Laboratory, Veterans Affairs Medical Center, North Chicago, IL
10/1989-02/1993 Research Assistant Professor, Departments of Medicine and Biological Chemistry, University of Health Sciences/The Chicago Medical School, North Chicago, IL
04/1993-11/1993 Assistant Professor, Department of Pharmacology, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ
12/1993-08/1999 Assistant Professor, Department of Experimental Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX
09/1999-08/2002 Assistant Professor, Section of Molecular Therapeutics, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, TX
09/1999-08/2002 Faculty, The Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center
01/1994-08/2002 Full Member, Graduate School of Biomedical Sciences, The University of Texas Health Sciences Center, Houston, TX
09/2002-04/2006 Associate Professor (Tenure-track), Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, TX
05/2006-Present Associate Professor (Tenured), Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center
10/2002-Present Member, Graduate School of Biomedical Sciences, Texas Tech University Health sciences Center
Research Interests:
Biochemical mechanisms of anticancer drug resistance and their modulation for improved therapies, DNA repair, Replication licensing, Posttranslational modifications, Cell cycle checkpoints, DNA topoisomerases, Polyamines, Gene expression mechanisms, Redox modulation of DNA repair and p53 tumor suppressor.
Honors & Memberships:
Recipient, Professor Giri Memorial Medal for the best Ph.D. thesis in Biochemistry, awarded in 1982 by the Indian Institute of Science, Bangalore, India
Recipient of a National Merit Scholarship from the Government of India, 1973-76
Member of the American Association for Cancer Research, 1990-present
Editorial Board for the Journal ‘Frontiers in Bioscience’, 2006-present
Managing Editor for the development of a special issue entitled “Molecular and Clinical Advances in Anticancer Drug Resistance” in Encyclopedia of Bioscience (scheduled in 2009)
Member, Oncology Course instructional Team of the Year, SOP, TTUHSC - 2003
Member, Oncology Course instructional Team of the Year, SOP, TTUHSC – 2004
First Place Research Award, TTUHSC School of Pharmacy Fifth Annual Research Days, 2006
Recipient of grant awards from American Cancer Society (Project Investigation Grant), National Cancer Institute (FIRST Award), Transcend Therapeutics, and Private Foundations such as the Wendy-will Case Cancer Fund, National Childhood Cancer Foundation, the Brain Tumor Center of UT M.D. Anderson Cancer Center, Association for Research of Childhood Cancer, Women’s Helalth Research Institute of Amarillo, and the Pediatric Brain Tumor Foundation of the United States.
Current Grant Support:
Principal Investigator, Regulation of MGMT by phosphorylation, NIH 1RO1 CA 97343
Principal Investigator, Induction of MGMT as a Strategy for Chemoprevention, NIH 1R03CA125872
Principal Investigator, DNA Repair Based Therapeutic Strategies for BRCA1 Mutant Breast Cancers – funded by the Laura Bush Institute for Women’s Health of Permian Basin (TTUHSC-Odessa/Midland)
Principal Investigator, Generation and Characterization of Cys141-Glutathionylation-specific Polyclonal Antibodies – Research agreement with and a grant funded by the Millipore Company
Publications:
1. Srivenugopal KS, and Adiga PR. The opiate receptor and opioid peptides (a review). J Indian Inst Sci 59:187-228, 1977.
2. Srivenugopal KS, and Adiga PR. Coexistence of two pathways of spermidine biosynthesis in Lathyrus sativus seedlings. FEBS Lett 112:260-264, 1980.
3. Srivenugopal KS, and Adiga PR. Artifactual staining of proteins on polyacrylamide gels by nitrobluetetrazolium chloride and phenazine methosulphate. Anal Biochem 101:215-220, 1980.
4. Srivenugopal KS, and Adiga PR. A simple procedure for purification of N-carbamylputrescine: application to assays of putrescine transcarbamylase and agmatine iminohydrolase activities. Anal Biochem 104:440-444, 1980.
5. Srivenugopal KS, and Adiga PR. Partial purification and properties of a transamidinase from Lathyrus sativus seedlings: involvement in homoarginine metabolism and amine interconversions. Biochem J 189:553-560, 1980.
6. Srivenugopal KS, and Adiga PR. Enzymic synthesis of symmetrical homospermidine in Lathyrus sativus seedlings. Biochem J 190:461-464, 1980.
7. Srivenugopal KS, and Adiga PR. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings: purification and properties of a multifunctional enzyme (putrescine synthase). J Biol Chem 256:9532-9541, 1981.
8. Srivenugopal KS, and Adiga PR. Putrescine synthase from Lathyrus sativus (grass pea) seedlings. Meth Enzymol 94:335-339, 1983.
9. Srivenugopal KS, and Adiga PR. Preparation and purification of N-carbamylputrescine and (ureido14C)-N-carbamylputrescine. Meth Enzymol, 94: 429- 430, 1983.
10. Srivenugopal KS, Lockshon D, and Morris DR. Escherichia coli DNA topoisomerase III: purification and characterization of a new type I enzyme. Biochemistry 23:1899-1906, 1984.
11. Srivenugopal KS, and Morris DR. Differential modulation by spermidine of reactions catalyzed by type I prokaryotic and eukaryotic topoisomerases. Biochemistry 24:4766-4771, 1985.
12. Wemmer DE. Srivenugopal KS, Reid BR, and Morris DR. Nuclear magnetic resonance studies of polyamine binding to a defined DNA sequence. J Mol Biol 185:457-469, 1985.
13. Srivenugopal KS and Morris DR. Modulation of the relaxing activity of Escherichia coli topoisomerase I by single-stranded DNA binding proteins. Biochem Biophys Res Commun 137:795-800, 1986.
14. Srivenugopal KS, Wemmer DE, and Morris DR. Aggregation of DNA by spermidine analogs: enzymatic and structural studies. Nucleic Acids Res 15:2563-2580, 1987.
15. Srivenugopal KS, and Schumer W. Alteration in the activities of DNA topoisomerase enzymes and O6-methylguanine-DNA methyltransferase in septic rat liver. Circulatory Shock 32:67-75, 1990.
16. Srivenugopal KS and Ali-Osman F. Stimulation and inhibition of 1,3-bis(2-chloroethyl)-1-nitrosourea induced strand breaks and interstrand crosslinking in Col E1 plasmid by polyamines and inorganic cations. Biochem Pharmacol 40:473-479, 1990.
17. Ali-Osman F, Srivenugopal KS, Berger MS, and Stein DE. DNA interstrand crosslinking and strand break repair in human glioma cell lines of varying 1.3-bis-(2-chloroethyl) -1-nitrosourea resistance. Anticancer Res 10:677-682, 1990.
18. Srivenugopal KS. Formation and disappearance of DNA interstrand cross-links in human colon tumor cell lines with different levels of resistance to chlorozotocin, Biochem Pharmacol 43:1159-1163, 1992.
19. Singh SP, Pullen GL, Srivenugopal KS, Yuan X-H, and Snyder AK. Decreased glucose transporter -1 gene expression and glucose uptake in fetal brain exposed to ethanol. Life Sci 51:527-536, 1992.
20. Singh SP, Srivenugopal KS, Yuan X-H, Jiang F, and Snyder AK. Effects of ethanol ingestion on glucose transporter-1 protein and mRNA levels in rat brain. Life Sci 53:1811-1819, 1993.
21. Chang CK, Moskal SF, Srivenugopal KS, and Schumer W. Altered levels of mRNA encoding enzymes of hepatic glucose metabolism in septic rats. Circulatory Shock 41:35-39, 1993.
22. Singh SP, Srivenugopal KS, Ehmann S, Yuan X-H, and Snyder AK. Insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins, and IGF-gene expression in the offspring of ethanol-fed rats. J Lab & Clin Medicine 124:183-192,1994.
23. Srivenugopal KS, Singh SP, Yuan X-H., and Ehmann S. Differential removal of insulin-like growth factor binding proteins in rat serum by solvent extraction procedures. Experientia 50:451-452, 1994.
24. Srivenugopal KS, Yuan X-H, Friedman HS, and Ali-Osman F. Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltrans-ferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1,3 bis(2-chloroethyl)-1-nitrosourea. Biochemistry 35:1328-1334, 1996.
25. Srivenugopal KS, and Ali-Osman F. Deletion and rearrangements inactivate the p16INK4 gene in human glioma cells. Oncogene 12:2029-2034, 1996.
26. Srivenugopal KS, and Ali-Osman F. Activity and distribution of the cysteine prodrug activating enzyme, 5-oxo-L-prolinase, in human normal and tumor tissues. Cancer Letters 117:105-111, 1997.
27. Srivenugopal KS, and Ali-Osman F. Coordinate up-regulation of cyclin-dependent kinase 4 and its inhibitor p16INK4 in human glioma cells following chloroethylnitrosourea-induced DNA damage. Int J Oncol. 11:1251-1256, 1997.
28. Srivenugopal KS, Mullapudi SRS, Shou J, Hazra TK, and Ali-Osman F. Protein phosphorylation is a regulatory mechanism for O6-alkylguanine-DNA alkyltransferase in human brain tumor cells. Cancer Res., 60:282-287, 2000.
29. Mullapudi SRS, Ali-Osman F, Shou J, and Srivenugopal KS. DNA repair protein O6-alkylguanine-DNA alkyltransferase is phosphorylated by two distinct and novel protein kinases in human brain tumor cells. Biochem J., 351:393-402, 2000.
30. Srivenugopal KS, Shou J, Mullapudi SRS, Lang FF Jr, Rao JS, and Ali-Osman F. Enforced expression of wild-type p53 curtails the transcription of the O6-methylguanine-DNA methyltransferase gene in human tumor cells and enhances their sensitivity to alkylating agents. Clin Cancer Res 7:1398-1409, 2001.
31. Ali-Osman F, Srivenugopal KS, Sawaya R., The DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. , 344, 687-688, 2001.
32. Srivenugopal KS, Mullapudi SRS, and Ali-Osman F. Phosphorylation of O6-alkylguanine-DNA alkyltransferase: experience with a GST-fusion protein and a new pull-down assay. Cancer Lett, 181, 87-93, 2002.
33. Shou J, Ali-Osman F, Multani AS, Pathak S, Fedi P, and Srivenugopal KS. Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells for apoptosis following alkylation damage of DNA. Oncogene 21, 878-889, 2002.
34. Srivenugopal KS and Ali-Osman F. The DNA repair protein O6-methylguanine-DNA methyltransferase is a proteolytic target for the E6 humanpapillomavirus oncoprotein, Oncogene 21, 5940-5945, 2002.
35. He Y, Fan S-Z, Srivenugopal KS, Jiang Y-G, Qin C. Enhanced chemosensitivity of p73a gene transferred into H1299 cell line of human lung adenocarcinoma. Journal of Medical Colleges of PLA (Peoples Liberation Army), 19: 151-156, 2004.
36. Niture SK, Velu CS, Bailey NI, Srivenugopal KS. S-thiolation mimicry: quantitative and kinetic analysis of redox status of protein cysteines by glutathione-affinity chromatography. Arch Biochem Biophys., 444(2):174-184, 2005.
37. Niture SK, Doneanu CE, Velu CS, Bailey NI, and Srivenugopal KS. Proteomic analysis of human O6-methylguanine-DNA mehyltransferase by affinity chromatography and tandem mass spectrometry. Biochem. Biophys. Res. Commun. , 337, 1176-1184, 2005.
38. Motlekar NA, Srivenugopal KS, Wachtel MS, Youan BB. Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels. J Drug Targeting 13(10):573-583, 2005.
39. Motlekar NA, Srivenugopal KS, Wachtel MS, Youan BB, Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation. J Pharm. Pharmacol. 58:591-598, 2006.
40. Niture SK, Rao, US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. International J of Oncology, 29, 1269-1278, 2006.
41. Motlekar NA, Srivenugopal, KS, Wachtel MS, Youan BB. Evaluation of the oral bioavailability of low molecular weight heparin formulated with glycyrrhetinic acid as permeation enhancer. Drug Development Research, 67 (2):166-174, 2006.
42. Wang Z, Zhang J, Zhang Y, Srivenugopal KS, Lim SH. SPAN-XB core promoter sequence is regulated in myeloma cells by specific CpG dinucleotides associated with the MeCP2 protein. Int J Cancer, 119, 2878-2884, 2006.
43. Rao PS, Mallya K. Srivenugopal KS, Balaji KC, Rao US. RNF2 interacts with the linker region of the human P-glycoprotein, Int J Oncol., 29, 1413-1419, 2006.
44. Niture SK, Velu CS, Smith QR, Bhat GJ, Srivenugopal KS. Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines, Carcinogenesis, 28, 378-389, 2007.
45. Velu CS, Niture SK, Doneanu CE, Pattabiraman N, Srivenugopal KS. Human p53 is inhibited by glutathionylation of cysteines present in the proximal DNA-binding domain during oxidative stress, Biochemistry 46, 7765-7780, 2007.
46. Hu Y, He Y, Srivenugopal KS, Fan S, Jiang Y. In vitro antitumor CTL response induced by dendritic cells transduced with deltaNp73a recombinant adenovirus, Oncology Reports 18, 1085-1091, 2007.
47. Rao PS, Bickel U, Srivenugopal KS, Rao US. Bap29varP, a variant of Bap29, influences the cell surface expression of the human P-glycoprotein. Int J Oncology, 32, 135-144, 2007.
48. Niture SK, Velu CS, Doneanu CE, Rao US, Pegg AE, and Srivenugopal KS. Redox regulation of DNA alkylation repair: Evidence for reversible inactivation of human MGMT by S-glutathionylation of the alkyl group acceptor cysteine 145. (Under review in J Biol Chem.)
49. Srivenugopal KS. Glutathionylation in redox signaling and implications in cancer therapeutics (Invited review) Antioxidants & Redox Signaling (In Press).
50. Satelli A, Rao PS, Gupta PK, Lockman P, Srivenugopal KS, and Rao US. Varied expression and localization of multiple galectins in human cancer cell lines and tumor specimens. (Oncology Reports, In Press)
Oral and Poster Presentations:
Approx. 75 abstracts at National and International Scientific Meetings.