Paul A. Voziyan, Ph.D.

Research Professor

paul.voziyan@vanderbilt.edu
Faculty Appointments
Research Professor of Medicine
Education
Ph.D., Biochemistry, National Academy of Sciences, Kiev, UkraineM.S., Shevchenko National University, Kyiv, Ukraine
Office Address
B-3113 MCN
FL 2358
Research Description
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.
Research Keywords
non-enzymatic glycation; protein modification; advanced glycation end products; diabetic complications; pyridoxamine
Publications
Brown KL, Darris C, Rose KL, Sanchez OA, Madu H, Avance J, Brooks N, Zhang MZ, Fogo A, Harris R, Hudson BG, Voziyan P. Hypohalous acids contribute to renal extracellular matrix damage in experimental diabetes. Diabetes [print-electronic]. 2015 Jun; 64(6): 2242-53. PMID: 25605804, PMCID: PMC4439565, PII: db14-1001, DOI: 10.2337/db14-1001, ISSN: 1939-327X.

Stec DF, Wang S, Stothers C, Avance J, Denson D, Harris R, Voziyan P. Alterations of urinary metabolite profile in model diabetic nephropathy. Biochem. Biophys. Res. Commun [print-electronic]. 2015 Jan 1/9/2015; 456(2): 610-4. PMID: 25499815, PMCID: PMC4287263, PII: S0006-291X(14)02168-8, DOI: 10.1016/j.bbrc.2014.12.003, ISSN: 1090-2104.

Yazlovitskaya EM, Voziyan PA, Manavalan T, Yarbrough WG, Ivanova AV. Cellular oxidative stress response mediates radiosensitivity in Fus1-deficient mice. Cell Death Dis. 2015; 6: e1652. PMID: 25695605, PMCID: PMC4669799, PII: cddis2014593, DOI: 10.1038/cddis.2014.593, ISSN: 2041-4889.

Grove KJ, Voziyan PA, Spraggins JM, Wang S, Paueksakon P, Harris RC, Hudson BG, Caprioli RM. Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles. J. Lipid Res [print-electronic]. 2014 May 5/26/2014; 55(7): 1375-85. PMID: 24864273, PMCID: PMC4076088, PII: jlr.M049189, DOI: 10.1194/jlr.M049189, ISSN: 0022-2275.

Yazlovitskaya EM, Uzhachenko R, Voziyan PA, Yarbrough WG, Ivanova AV. A novel radioprotective function for the mitochondrial tumor suppressor protein Fus1. Cell Death Dis. 2013; 4: e687. PMID: 23788044, PMCID: PMC3702292, PII: cddis2013212, DOI: 10.1038/cddis.2013.212, ISSN: 2041-4889.

Borza CM, Su Y, Chen X, Yu L, Mont S, Chetyrkin S, Voziyan P, Hudson BG, Billings PC, Jo H, Bennett JS, Degrado WF, Eckes B, Zent R, Pozzi A. Inhibition of integrin a2ß1 ameliorates glomerular injury. J. Am. Soc. Nephrol [print-electronic]. 2012 Jun; 23(6): 1027-38. PMID: 22440900, PMCID: PMC3358756, PII: ASN.2011040367, DOI: 10.1681/ASN.2011040367, ISSN: 1533-3450.

Chetyrkin S, Mathis M, Hayes McDonald W, Shackelford X, Hudson B, Voziyan P. Pyridoxamine protects protein backbone from oxidative fragmentation. Biochem. Biophys. Res. Commun [print-electronic]. 2011 Aug 8/5/2011; 411(3): 574-9. PMID: 21763683, PMCID: PMC3153140, PII: S0006-291X(11)01201-0, DOI: 10.1016/j.bbrc.2011.06.188, ISSN: 1090-2104.

Chetyrkin S, Mathis M, Pedchenko V, Sanchez OA, McDonald WH, Hachey DL, Madu H, Stec D, Hudson B, Voziyan P. Glucose autoxidation induces functional damage to proteins via modification of critical arginine residues. Biochemistry [print-electronic]. 2011 Jul 7/12/2011; 50(27): 6102-12. PMID: 21661747, PMCID: PMC3140462, DOI: 10.1021/bi200757d, ISSN: 1520-4995.

Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, Wilson CB, Hudson BG. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N. Engl. J. Med. 2010 Jul 7/22/2010; 363(4): 343-54. PMID: 20660402, PMCID: PMC4144421, PII: 363/4/343, DOI: 10.1056/NEJMoa0910500, ISSN: 1533-4406.

Pozzi A, Zent R, Chetyrkin S, Borza C, Bulus N, Chuang P, Chen D, Hudson B, Voziyan P. Modification of collagen IV by glucose or methylglyoxal alters distinct mesangial cell functions. J. Am. Soc. Nephrol [print-electronic]. 2009 Oct; 20(10): 2119-25. PMID: 19608705, PMCID: PMC2754111, PII: ASN.2008080900, DOI: 10.1681/ASN.2008080900, ISSN: 1533-3450.

Thotala D, Chetyrkin S, Hudson B, Hallahan D, Voziyan P, Yazlovitskaya E. Pyridoxamine protects intestinal epithelium from ionizing radiation-induced apoptosis. Free Radic. Biol. Med [print-electronic]. 2009 Sep 9/15/2009; 47(6): 779-85. PMID: 19540915, PMCID: PMC2739572, PII: S0891-5849(09)00367-0, DOI: 10.1016/j.freeradbiomed.2009.06.020, ISSN: 1873-4596.

Pozzi A, Voziyan PA, Hudson BG, Zent R. Regulation of matrix synthesis, remodeling and accumulation in glomerulosclerosis. Curr. Pharm. Des. 2009; 15(12): 1318-33. PMID: 19355971, ISSN: 1873-4286.

Chetyrkin SV, Mathis ME, Ham AJ, Hachey DL, Hudson BG, Voziyan PA. Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine. Free Radic. Biol. Med [print-electronic]. 2008 Apr 4/1/2008; 44(7): 1276-85. PMID: 18374270, PII: S0891-5849(07)00626-0, DOI: 10.1016/j.freeradbiomed.2007.09.016, ISSN: 0891-5849.

Chetyrkin SV, Zhang W, Hudson BG, Serianni AS, Voziyan PA. Pyridoxamine protects proteins from functional damage by 3-deoxyglucosone: mechanism of action of pyridoxamine. Biochemistry [print-electronic]. 2008 Jan 1/22/2008; 47(3): 997-1006. PMID: 18161948, DOI: 10.1021/bi701190s, ISSN: 0006-2960.

Davies SS, Brantley EJ, Voziyan PA, Amarnath V, Zagol-Ikapitte I, Boutaud O, Hudson BG, Oates JA, Roberts LJ. Pyridoxamine analogues scavenge lipid-derived gamma-ketoaldehydes and protect against H2O2-mediated cytotoxicity. Biochemistry [print-electronic]. 2006 Dec 12/26/2006; 45(51): 15756-67. PMID: 17176098, PMCID: PMC2597444, DOI: 10.1021/bi061860g, ISSN: 1520-4995.

Zent R, Yan X, Su Y, Hudson BG, Borza DB, Moeckel GW, Qi Z, Sado Y, Breyer MD, Voziyan P, Pozzi A. Glomerular injury is exacerbated in diabetic integrin alpha1-null mice. Kidney Int [print-electronic]. 2006 Aug; 70(3): 460-70. PMID: 16775606, PII: 5000359, DOI: 10.1038/sj.ki.5000359, ISSN: 0085-2538.

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 Oct; 54(10): 2952-60. PMID: 16186398, PII: 54/10/2952, ISSN: 0012-1797.

Voziyan PA, Hudson BG. Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage. Cell. Mol. Life Sci. 2005 Aug; 62(15): 1671-81. PMID: 15905958, DOI: 10.1007/s00018-005-5082-7, ISSN: 1420-682X.

Voziyan PA, Hudson BG. Pyridoxamine: the many virtues of a maillard reaction inhibitor. Ann. N. Y. Acad. Sci. 2005 Jun; 1043: 807-16. PMID: 16037308, PII: 1043/1/807, DOI: 10.1196/annals.1333.093, ISSN: 0077-8923.

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 Jan; 67(1): 53-60. PMID: 15610227, PII: KID054, DOI: 10.1111/j.1523-1755.2005.00054.x, ISSN: 0085-2538.

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(2-3): 183-8. PMID: 16211517, DOI: 10.1007/s10969-005-2646-6, ISSN: 1345-711X.

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 [print-electronic]. 2003 Nov 11/21/2003; 278(47): 46616-24. PMID: 12975371, PII: M307155200, DOI: 10.1074/jbc.M307155200, ISSN: 0021-9258.

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 [print-electronic]. 2002 Feb 2/1/2002; 277(5): 3397-403. PMID: 11729198, PII: M109935200, DOI: 10.1074/jbc.M109935200, ISSN: 0021-9258.

Voziyan PA, Fisher MT. Polyols induce ATP-independent folding of GroEL-bound bacterial glutamine synthetase. Arch. Biochem. Biophys. 2002 Jan 1/15/2002; 397(2): 293-7. PMID: 11795885, PII: S0003986101926207, DOI: 10.1006/abbi.2001.2620, ISSN: 0003-9861.

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 Aug; 89(8): 1036-45. PMID: 10906727, PII: 10.1002/1520-6017(200008)89:8<1036::AID-JPS8>3.0.CO;2-5, ISSN: 0022-3549.

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((12)): 2405-12.

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 Oct 10/30/1998; 273(44): 28677-81. PMID: 9786862, ISSN: 0021-9258.

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 Sep 9/25/1998; 273(39): 25073-8. PMID: 9737964, ISSN: 0021-9258.

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 Jan 1/15/1998; 1389(2): 91-100. PMID: 9461250, ISSN: 0006-3002.

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 Aug 8/19/1997; 36(33): 10082-8. PMID: 9254603, PII: bi970829z, DOI: 10.1021/bi970829z, ISSN: 0006-2960.

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 Sep 9/24/1996; 35(38): 12526-31. PMID: 8823189, PII: bi960562o, DOI: 10.1021/bi960562o, ISSN: 0006-2960.

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 Jul 7/17/1995; 212(2): 479-86. PMID: 7626062, PII: S0006-291X(85)71995-X, DOI: 10.1006/bbrc.1995.1995, ISSN: 0006-291X.

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 Aug 8/11/1994; 1223(1): 133-40. PMID: 8061045, PII: 0167-4889(94)90082-5, ISSN: 0006-3002.

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 May 5/16/1994; 79(2): 175-9. PMID: 8019976, ISSN: 0304-3835.

Voziyan PA, Goldner CM, Melnykovych G. Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity. Biochem. J. 1993 Nov 11/1/1993; 295 ( Pt 3): 757-62. PMID: 8240288, PMCID: PMC1134625, ISSN: 0264-6021.

Available Postdoctoral Position Details
Posted: 10/2/2017

We are looking for a highly motivated postdoctoral fellow to join the Billy Hudson lab in the Division of Nephrology and Hypertension. The research program is focused on structure and function of renal extracellular matrix in normal and disease states. The successful candidate will be a part of highly motivated and productive research team.

The ideal applicant will have PhD in Biochemistry, Cell Biology, or related field and demonstrated experience with protein expression, purification and analysis, cell culture, and immunodetection approaches. Responsibilities include designing and implementing experiments, data collection and analysis, abstract and manuscript preparation and scientific presentations. The successful candidate should have a demonstrated ability to work both independently and collaboratively, possess strong oral and written communication skills.

Qualified applicants should submit a cover letter describing previous research experience as well as current interests, curriculum vitae and contact details of three references to Paul Voziyan, Ph.D. by email at paul.voziyan@vanderbilt.edu.