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Associate Dean of Research
Director, Biomedical Sciences PhD Program
Professor of Pharmacology
sreejay@uwyo.edu • (307) 766-6138 • HS 484
Best Mode of Communication: E-mail
B. Pharm. 1989, College of Pharmaceutical Sciences, Manipal, Mangalore University, India
M. Pharm. 1991, College of Pharmaceutical Sciences, Manipal, Mangalore University, India
Ph.D. 1996, College of Pharmaceutical Sciences, Manipal, Mangalore University, India
2014- Professor, University of Wyoming, School of Pharmacy, Laramie, Wyoming
2008-2014- Associate Professor, University of Wyoming, School of Pharmacy, Laramie, Wyoming
2002-2008- Assistant Professor, University of Wyoming, School of Pharmacy, Laramie, Wyoming
1998-2002- Post Doctoral Fellow, Department of Physiology, University of Tennessee, Memphis, Tennessee
1996-1998-Research Fellow, Department of Medicine II, Klinikum Grosshadern, Ludwig Maximillians University, Munich, Germany
Type-2 diabetes is an emerging health problem. Targeting, insulin resistance, which occurs long before the onset of frank type-2 diabetes is an attractive strategy to preempt diabetes and its complication. Our lab is interested in understanding the molecular mechanisms leading to insulin resistance. Our ultimate goal is to design and develop novel therapeutic strategies to prevent or treat this condition. We use the general techniques of cell biology such as tissue culture, Western blotting, immunoprecipitation, immunocytochemistry and the techniques of molecular biology, including the use of adenoviral vectors for transgene expression and knock-out animals to address our research questions. Outcome of our studies will help in understanding the mechanisms involved in the pathogenesis of diabetes and may aid in developing novel therapeutic strategies to treat or prevent these conditions. We have characterized novel low molecular-weight chromium complexes that can alleviate insulin resistance by augmenting insulin signaling both in cultured myotubes and in genetic and nutritional animal models of insulin resistance. In addition to insulin resistance, we are also interested in cardiac complications associated with insulin resistance. Our recent studies have unraveled roles cathepsin K and endothelin-receptor-A in obesity associated cardiometabolic dysfunctions.
Type-2 diabetes and cardiovascular diseases
Pharmacology
Clinical Toxicology
Advanced Cardiovascular Physiology
Molecular and Cellular Basis for Diseases
Note: *Graduate Student; **Post-doctoral Fellow; #High-school student; ##Undergraduate
1. Hua Y*, Nair S (2014) Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications Biochim Biophys Acta - Molecular Basis of Disease (in press)
2. Kandadi MR**, Panzhinskiy E*, Roe ND*, Nair S, Hu D, Sun A. Deletion of Protein Tyrosine Phosphatase 1B Knockout Rescues against Myocardial Anomalies in High Fat Diet-Induced Obesity: Role of AMPK-Dependent Autophagy. Biochim Biophys Acta (in press)
3. Zhu X, Hu N, Chen X, Zhu MZ, Dong H, Xu X, Luo F, Hua Y, Nair S, Samson WK, Xiong L, Ren J. Neuronostatin Attenuates Myocardial Contractile Function through Inhibition of Sarcoplasmic Reticulum Ca-ATPase in Murine Heart. Cell Physiol Biochem. 33:1921-19, 2014
4. Panzhinskiy E*, Lapchak PA, Topchiy E, Lehmann TE, Ren J, Nair S. A Novel Neurotrophic Curcumin Analog Mitigates Obesity-Associated Insulin Resistance. J Pharmacol Exp Ther. 349: 248-57, 2014
5. Xu X*, Hua Y*, Nair S, Ren J. Macrophage Migration Inhibitory Factor Deletion Exacerbates Pressure Overload-Induced Cardiac Hypertrophy through Mitigating Autophagy. Hypertension. 63: 490-9, 2014
6. Panzhinskiy E*, Ren J, Nair S: Protein tyrosine phosphatase 1B and insulin resistance: Role of endoplasmic reticulum stress/reactive oxygen species/nuclear factor kappa B axis, PLoS One. 18: e77228, 2013
7. Kandadi MR**, Hua Y*, Zhu M, Turdi S*, Nathanielsz PW, Ford SP, Nair S, Ren J: Influence of Gestational Overfeeding and Obesity on Myocardial Pro-inflammatory Mediators in Fetal Sheep Heart. J Nutr Biochem. 23:1982-90, 2013
8. Ceylan-Isik A**, Kandadi MR**, Chicco AJ, Ren J, Nair S: Apelin Alleviates High-Fat Diet-Induced Myocardial Contractile Dysfunction. J Mol Cell Cardiol. 63: 4-13, 2013
9. Hua Y*, Dolence J**, Ramanan S##, Ren J, Nair S: Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation. Mol Nutr Food Res 1611-1618, 2013
10. Panzhinskiy E*, Ren J, Nair S: Protein Tyrosine Phosphatase 1B as a Therapeutic Target in Obesity Related Conditions. Curr Med Chem. 21: 2609-25, 2013
11. Hua H*, Xu X*, Shi GP, Ren J, Nair S: Cathepsin-K Knockout Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction. Hypertension. 61: 1184-92, 2013
12. Dong M*, Hu N, Hua Y*, Xu X*, Kandadi MR**, Guo R, Jiang S, Nair S, Hu D##, Ren J: Chronic Akt activation attenuated lipopolysaccharide-induced cardiac dysfunction via Akt/GSK3β-dependent inhibition of apoptosis and ER stress. Biochim Biophys Acta.1832: 848-863, 2013
13. Panzhinskiy E*, Hua Y*, Culver B, Nair S: Endoplasmic reticulum stress up-regulates protein-tyrosine phosphatase 1B expression and impairs glucose uptake in cultured myotubes. Diabetologia, 16: 598-608, 2013
14. Hua Y*, Zhang Y, Dolence J**, Shi GP, Ren J, Nair S: Cathepsin K Knockout Mitigates High-Fat Diet-Induced Cardiac Hypertrophy and Contractile Dysfunction. Diabetes, 62: 498-509, 2013
15. Ceylan-Isik AF**, Dong M, Zhang Y, Dong F, Turdi S*, Nair S, Yanagisawa M, Ren J: Cardiomyocyte-specific deletion of endothelin receptor A rescues aging-associated cardiac hypertrophy and contractile dysfunction: Role of autophagy. Basic Res Cardiol, 108:335, 2013
16. Xu X*, Hua Y*, Nair S, Zhang Y, Ren J: Akt2 knockout preserves cardiac function in high-fat diet-induced obesity by rescuing cardiac autophagosome maturation. J Mol Cell Biol, 5:61-63, 2013
17. Nair S and Ren J.: Autophagy and cardiovascular aging: Lessons learned from rapamycin. Cell Cycle, 11: 2092-2099, 2012
18. Hua H*, Clark S, Ren J, Sreejayan N: Molecular mechanisms of chromium in alleviating insulin resistance. J. Nutr. Biochem, 23: 313-319, 2012
19. Palanichamy K**, Sreejayan N, Ontko A: Overcoming cisplatin resistance using gold (III) mimics: Anticancer activity of novel gold(III) polypyridyl complexes. J Inorg Biochem, 106: 32-42, 2011
20. Ceylan-Isik AF**, Sreejayan N, Ren J.: Endoplasmic reticulum chaperon tauroursodeoxycholic acid alleviates obesity-induced myocardial contractile dysfunction J. Mol. Cell Cardiol. 50: 107-16, 2011
21. Kandadi MR*, Unnikrishnan MK, Warrier AK, Du M, Ren J, Sreejayan N: Chromium (d-phenylalanine)3 alleviates high fat-induced insulin resistance and lipid abnormalities. J Inorg Biochem. 105: 58-62, 2010
22. Sreejayan N, Marone PA, Lau FC, Yasmin T, Bagchi M, Bagchi D: Safety and toxicological evaluation of a novel chromium(III) dinicotino-cystinate complex. Toxicol Mech Methods, 20: 321-33, 2010
23. Zhao J*, Yue W, Zhu MJ, Sreejayan N, Du M: AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of β-catenin at Ser 552. Biochem. Biophys. Res. Commun. 395: 146-151, 2010
24. Hua Y*, Kandadi MR*, Zhu M, Ren J, Sreejayan N: Tauroursodeoxycholic Acid Attenuates Lipid Accumulation in Endoplasmic Reticulum-Stressed Macrophages. J Cardiovasc Pharmacol, 55: 49-55, 2010
25. Kandadi MR*, Rajanna PK, Unnikrishnan MK, Boddu SP, Hau Y, Li J, Du M, Ren J, Sreejayan N: 2-(3,4-Dihydro-2H-pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), a novel, synthetic small molecule that alleviates insulin resistance and lipid abnormalities. Biochem Pharmacol. 79: 623-31, 2010
26. Zhao P*, Wang J, Ma H, Xiao Y, He L, Tong C, Wang Z, Zheng Q, Dolence EK, Sreejayan N, Ren J, Li J: A newly synthetic chromium complex-chromium (D-phenylalanine)3 activates AMP-activated protein kinase and stimulates glucose transport. Biochem Pharmacol 77:1002-1010, 2009
27. Dong F*, Hua Y, Zhao P, Ren J, Du M, Sreejayan N: Chromium Supplement Inhibits Skeletal Muscle Atrophy in Hindlimb Suspended Mice. J Nutr Biochem 12: 992-999, 2009
28. Sreejayan N, Yang X**, Palanichamy K**, Dolence K, Ren J: Antioxidant properties of argpyrimidine. Eur J Pharmacol 593:30-35, 2008
29. Sreejayan N, Dong F*, Kandadi MR*, Yang XP**, Ren J: Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity 16:1331-1337, 2008
30. Ren J, Duan JH, Thomas DP, Yang XP**, Sreejayan N, Sowers JR, Leri A, Kajstura J, Gao F, Anversa P: IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction. Am J Physiol -Reg Integr Comp Physiol 94: R793-R802, 2008
31. Liu Y, Dolence J**, Ren J, Rao M, Sreejayan N: Inhibitory effect of dehydrozingerone on vascular smooth muscle cell function. J Cardiovasc Pharmacol 52: 422-429, 2008
32. Jungst C, Sreejayan N, Zundt B, Muller I, Spelsberg FW, Huttl TP, Kullak-Ublick GA, del Pozo R, Jungst D, von Ritter C: Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones. Eur J Clin Invest 38:634-639, 2008
33. Dong F*, Kandadi MR*, Ren J, Sreejayan N: Chromium (D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice. J Nutr 138:1846-1851, 2008
34. Stratton MS##, Yang X**, Sreejayan N, Ren J: Impact of insulin-like growth factor-I on migration, proliferation and Akt-ERK signaling in early and late-passages of vascular smooth muscle cells. Cardiovasc Toxicol 7:273-281, 2007
35. Sreejayan N, Yang X**: Isolation and functional studies of rat aortic smooth muscle cells. Methods Mol Med 139:283-292, 2007
36. Li Q, Yang X**, Sreejayan N, Ren J: Insulin-like growth factor I deficiency prolongs survival and antagonizes paraquat-induced cardiomyocyte dysfunction: role of oxidative stress. Rejuvenation Res 10:501-512, 2007
37. Jungst C, Sreejayan N, Eder MI, von Stillfried N, Zundt B, Spelsberg FW, Kullak-Ublick GA, Jungst D, von Ritter C: Lipid peroxidation and mucin secretagogue activity in bile of gallstone patients. Eur J Clin Invest 37:731-736, 2007
38. Fang CX*, Yang XP**, Sreejayan N, Ren J: Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human neuroblastoma cells. Exp Neruol 203:196-204, 2007
39. Dong F*, Yang XP**, Sreejayan N, Ren J: Chromium (D-phenylalanine)3 improves obesity-induced cardiac contractile defect in ob/ob mice. Obesity 15:2699-2711, 2007
40. Dong F*, Li Q, Sreejayan N, Nunn JM, Ren J: Metallothionein prevents high-fat diet induced cardiac contractile dysfunction: role of peroxisome proliferator activated receptor gamma coactivator 1 alpha and mitochondrial biogenesis. Diabetes 56:2201-2212, 2007
41. Yang XP**, Thomas DP, Zhang XC, Culver BW, Alexander BM, Murdoch WJ, Rao MNA, Tulis DA, Ren J, Sreejayan N: Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation. Arterioscler Thromb Vasc Biol 26:85-90, 2006
42. Yang XP**, Li SY, Dong F, Ren J, Sreejayan N: Insulin-sensitizing and cholesterol-lowering effects of chromium (D-Phenylalanine)3. J Inorg Biochem 100:1187-1193, 2006
43. Yang X**, Doser TA, Fang CX, Nunn JM, Janardhanan R**, Zhu M, Sreejayan N, Quinn MT, Ren J: Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J 20:1024-1026, 2006
44. Wold LE, Ceylan-Isik AF**, Fang CX*, Yang XP**, Li SY, Sreejayan N, Privratsky JR, Ren J: Metallothionein alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of Ca2+ cycling proteins, NADPH oxidase, poly(ADP-Ribose) polymerase and myosin heavy chain isozyme. Free Rad Biol Med 40:1419-1429, 2006
45. Li SY**, Yang X**, Ceylan-Isik AF**, Du M, Sreejayan N, Ren J: Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch. Diabetologia 49:1434-1446, 2006
46. Fang CX*, Doser TA, Yang X**, Sreejayan N, Ren J: Metallothionein antagonizes aging-induced cardiac contractile dysfunction: role of PTP1B, insulin receptor tyrosine phosphorylation and Akt. Aging Cell 5:177-185, 2006
47. Yang XP**, Zhu MJ, Sreejayan N, Ren J, Du M: Angiotensin II promotes smooth muscle cell proliferation and migration through release of heparin-binding epidermal growth factor and activation of EGF-receptor pathway. Mol Cells 20:263-270, 2005
48. Yang XP**, Sreejayan N, Ren J: Views from within and beyond - Narratives of cardiac contractile dysfunction under senescence. Endocrine 26:127-137, 2005
49. Yang XP**, Palanichamy K**, Ontko AC, Rao MNA, Fang CX, Ren J, Sreejayan N: A newly synthetic chromium complex - chromium (phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance. FEBS Letts 579:1458-1464, 2005
50. Li SY, Du M, Dolence EK, Fang CX*, Mayer GE, Ceylan-Isik AF, LaCour KH, Yang X, Wilbert CJ, Sreejayan N, Ren J: Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification. Aging Cell 4:57-64, 2005
51. Yigzaw Y, Poppleton HM, Sreejayan N, Hassid A, Patel TB: Protein-tyrosine phosphatase-1B (PTP1B) mediates the anti-migratory actions of sprouty. J Biol Chem 278:284-288, 2003
52. Sreejayan N, Lin Y, Hassid A: NO attenuates insulin signaling and motility in aortic smooth muscle cells via protein tyrosine phosphatase 1B-mediated mechanism. Arterioscler Thromb Vasc Biol 22:1086-1092, 2002
53. Chang Y, Ceacareanu B, Dixit M, Sreejayan N, Hassid A: Nitric oxide-induced motility in aortic smooth muscle cells: role of protein tyrosine phosphatase SHP-2 and GTP-binding protein Rho. Circ Res 91:390-397, 2002
54. Sreejayan N, Wittig BM, von Stillfried N, Hennicke MS, Meyer G, Stieber P, Lamerz R, von Ritter C: Human biliary mucin binds to E-selectin: a possible role in modulation of inflammation. Am J Physiol Gastrointest Liver Physiol 280:G1043-1048, 2001
55. Wildhirt SM, Schulze C, Conrad N, Sreejayan N, Reichenspurner H, von Ritter C, Reichart B: Reduced myocardial cellular damage and lipid peroxidation in off-pump versus conventional coronary artery bypass grafting. Eur J Med Res 5:222-228, 2000
56. Sreejayan N, von Ritter C: Lipid peroxidation in bile: Role of bile acids and the effect on biliary epithelial cell function. Pathophysiol 5 225-232, 1999
57. Ganesh Pai C, Sreejayan N, Rao MN: Evidence for oxidant stress in chronic pancreatitis. Ind J Gastroenterol 18:156-157, 1999
58. Sreejayan N, von Ritter C: Effect of bile acids on lipid peroxidation: The role of iron. Free Rad Biol Med 25:50-56, 1998
59. Sreejayan N, Rao MNA, Priyadarsini KI, Devasagayam TPA: Inhibition of radiation-induced lipid peroxidation by curcumin. Int J Pharm 151:127-130, 1997
60. Sreejayan, Rao MNA: Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol 49:105-107, 1997
61. Guha SN, Priyadarsini KI, Devasagayam TPA, Sreejayan N, Rao MNA: Hydroxyl radical reactions of (4-hydroxy, 3-methoxy-5-bromophenyl) pentenone, a curcuminoid antioxidant. Rad Phy Chem 49:43-46, 1997
62. Sreejayan N, Rao MNA: Free radical scavenging activity of curcuminoids. Arzneimittel-Forschung/Drug Res 46:169-171, 1996
63. Subramanian M*, Sreejayan N*, Rao MNA, Devasagayam TPA, Singh BB: Diminution of Singlet Oxygen-Induced DNA-Damage by Curcumin and Related Antioxidants. Mutat Res 311:249-255, 1994 (*equal first authorship)
64. Sreejayan N, Rao MNA: Curcuminoids as Potent Inhibitors of Lipid-Peroxidation. J Pharm Pharmacol 46:1013-1016, 1994
65. Sreejayan N, Rao MNA: Curcumin Inhibits Iron-Dependent Lipid-Peroxidation. Int J Pharm 100:93-97, 1993
66. Sreejayan N, Rao MNA: Oxygen free radical scavenging by Momordica charantia extract. Fitoterapia LXII:344-346, 1991
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