Center for Matrix Biology - Vanderbilt University and Medical Center

Paul Voziyan, Ph.D.
Research Associate Professor in the Department of Medicine

	Office Address:	B-3113 MCN
	Mailing Address:	B-3113 MCN Nashville, TN 2358
	Lab address:
	Phone:	2-2089
		email

Secondary appointment in the Biochemistry department.

Research Summary

In diabetes, the elevated levels of glucose and its degradation products cause the increase in specific chemical modifications of proteins called advanced glycation end products or AGEs. Our research focuses on uncovering the mechanisms by which such protein modifications could cause diabetic complications, in particular diabetic nephropathy. Studies include (i) biochemical characterization of AGE modifications and their effects on protein structure and function; (ii) effects of AGE-modified proteins on cell signaling and cell behavior; (iii) determination of global changes in cellular proteome caused by AGE-modified proteins.

We also focus on development of novel strategies to inhibit AGE modifications and preserve protein functionality in diabetes. In particular, we investigate mechanisms of action of pyridoxamine, a prospective drug for treatment of diabetic nephropathy.

In our laboratory and through multiple collaborations we employ such experimental methods as nuclear magnetic resonance, X-ray crystallography, mass-spectrometry, analysis of protein conformation by absorbance and fluorescence techniques, high performance liquid chromatography, cell culture and animal models.

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Associated initiative(s):

Diabetic Complications

Fibrosis

Career opportunities:
None currently available

Selected Publications

» Voziyan, PA, Hudson, BG Pyridoxamine: the many virtues of a maillard reaction inhibitor Ann N Y Acad Sci 2005. 1043:807-16

» Voziyan, PA, Hudson, BG Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage Cell Mol Life Sci 2005. 62:1671-1681

» Voziyan, PA, Johnston, M, Chao, A, Bomhoff, G, Fisher, MT Designing a High Throughput Refolding Array Using a Combination of the GroEL Chaperonin and Osmolytes J Struct Funct Genomics 2005. 6:183-8

» Chetyrkin, SV, Kim, D, Belmont, JM, Scheinman, JI, Hudson, BG, Voziyan, PA Pyridoxamine lowers kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria Kidney Int 2005. 67:53-60

» Pedchenko, VK, Chetyrkin, SV, Chuang, P, Ham, AJ, Saleem, MA, Mathieson, PW, Hudson, BG, Voziyan, PA Mechanism of perturbation of integrin-mediated cell-matrix interactions by reactive carbonyl compounds and its implication for pathogenesis of diabetic nephropathy Diabetes 2005. 54:2952-60

» Voziyan, PA, Khalifah, RG, Thibaudeau, C, Yildiz, A, Jacob, J, Serianni, AS, Hudson, BG Modification of proteins in vitro by physiological levels of glucose: pyridoxamine inhibits conversion of Amadori intermediate to advanced glycation end-products through binding of redox metal ions J Biol Chem 2003. 278:46616-24

» Voziyan, PA, Fisher, MT Polyols induce ATP-independent folding of GroEL-bound bacterial glutamine synthetase Arch Biochem Biophys 2002. 397:293-7

» Voziyan, PA, Metz, TO, Baynes, JW, Hudson, BG A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation J Biol Chem 2002. 277:3397-403

» Voziyan PA, Fisher MT Chaperonin-assisted folding of glutamine synthetase under nonpermissive conditions: off-pathway aggregation propensity does not determine the co-chaperonin requirement Protein Sci 2000 . 9:2405-12

» Voziyan, PA, Jadhav, L, Fisher, MT Refolding a glutamine synthetase truncation mutant in vitro: identifying superior conditions using a combination of chaperonins and osmolytes J Pharm Sci 2000. 89:1036-45

» Voziyan, PA, Tieman, BC, Low, CM, Fisher, MT Changing the nature of the initial chaperonin capture complex influences the substrate folding efficiency J Biol Chem 1998. 273:25073-8

» Smith, KE, Voziyan, PA, Fisher, MT Partitioning of rhodanese onto GroEL. Chaperonin binds a reversibly oxidized form derived from the native protein J Biol Chem 1998. 273:28677-81

» Tremblay, JM, Voziyan, PA, Helmkamp, GM, Yarbrough, LR The C-terminus of phosphatidylinositol transfer protein modulates membrane interactions and transfer activity but not phospholipid binding Biochim Biophys Acta 1998. 1389:91-100

» Voziyan, PA, Tremblay, JM, Yarbrough, LR, Helmkamp, GM Importance of phospholipid in the folding and conformation of phosphatidylinositol transfer protein: comparison of apo and holo species Biochemistry 1997. 36:10082-8

» Voziyan, PA, Tremblay, JM, Yarbrough, LR, Helmkamp, GM Truncations of the C-terminus have different effects on the conformation and activity of phosphatidylinositol transfer protein Biochemistry 1996. 35:12526-31

» Voziyan, PA, Haug, JS, Melnykovych, G Mechanism of farnesol cytotoxicity: further evidence for the role of PKC-dependent signal transduction in farnesol-induced apoptotic cell death Biochem Biophys Res Commun 1995. 212:479-86

» Adany, I, Yazlovitskaya, EM, Haug, JS, Voziyan, PA, Melnykovych, G Differences in sensitivity to farnesol toxicity between neoplastically- and non-neoplastically-derived cells in culture Cancer Lett 1994. 79:175-9

» Haug, JS, Goldner, CM, Yazlovitskaya, EM, Voziyan, PA, Melnykovych, G Directed cell killing (apoptosis) in human lymphoblastoid cells incubated in the presence of farnesol: effect of phosphatidylcholine Biochim Biophys Acta 1994. 1223:133-40

» Voziyan, PA, Goldner, CM, Melnykovych, G Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity Biochem J 1993. 295 ( Pt 3):757-62