Vanderbilt-Ingram Cancer Center

The VICC.ORG Investigator Directory

Roy Zent, M.D., Ph.D.

Assistant Professor of Medicine (Nephrology), Cancer Biology, and Cell & Developmental Biology
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
C-3210 Medical Center North
Nashville, TN 37232-2372
615-322-4632

Research Description:

The laboratory works on the basic role of integrins in epithelial cell biology. We utilize the kidney as a model system and perform biochemical techniques, cell biology and transgenic mice to understand the basic mechanisms whereby integrin-ECM interactions modify cell function. In addition, in collaboration with Dr. Charles Sanders, we perform structural functions on integrins utilizing NMR.

Publications:

• Lu, Z, Van Horn, WD, Chen, J, Mathew, S, Zent, R, Sanders, CR Bicelles at low concentrations. Mol Pharm, 9(4), 752-61, 2012.
• Bulus, N, Feral, C, Pozzi, A, Zent, R CD98 Increases Renal Epithelial Cell Proliferation by Activating MAPKs. PLoS One, 7(6), e40026, 2012.
• Pozzi, A, Zent, R Hold tight or you''ll fall off: CD151 helps podocytes stick in high-pressure situations. J Clin Invest, 122(1), 13-6, 2012.
• Gewin, L, Zent, R How Does TGF-β Mediate Tubulointerstitial Fibrosis. Semin Nephrol, 32(3), 228-35, 2012.
• 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 α2β1 ameliorates glomerular injury. J Am Soc Nephrol, 23(6), 1027-38, 2012.
• Yu, L, Su, Y, Paueksakon, P, Cheng, H, Chen, X, Wang, H, Harris, RC, Zent, R, Pozzi, A Integrin α1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy. Kidney Int, 81(11), 1086-97, 2012.
• Pozzi, A, Zent, R Extracellular matrix receptors in branched organs. Curr Opin Cell Biol, 2011.
• Mathew, S, Chen, X, Pozzi, A, Zent, R Integrins in renal development. Pediatr Nephrol, 2011.
• Pozzi, A, Zent, R TGF-β Sequestration by Mesangial Cell Integrin αvβ8 A Novel Mechanism of Glomerular Endothelial Cell Regulation. Am J Pathol, 178(2), 485-9, 2011.
• Clark, PE, Polosukhina, D, Love, H, Correa, H, Coffin, C, Perlman, EJ, de Caestecker, M, Moses, HL, Zent, R β-Catenin and K-RAS synergize to form primitive renal epithelial tumors with features of epithelial Wilms'' tumors. Am J Pathol, 179(6), 3045-55, 2011.
• Chen, X, Whiting, C, Borza, C, Hu, W, Mont, S, Bulus, N, Zhang, MZ, Harris, RC, Zent, R, Pozzi, A Integrin alpha1beta1 regulates epidermal growth factor receptor activation by controlling peroxisome proliferator-activated receptor gamma-dependent caveolin-1 expression. Mol Cell Biol, 30(12), 3048-58, 2010.
• Borza, CM, Chen, X, Mathew, S, Mont, S, Sanders, CR, Zent, R, Pozzi, A Integrin {alpha}1{beta}1 promotes caveolin-1 dephosphorylation by activating T cell protein-tyrosine phosphatase. J Biol Chem, 285(51), 40114-24, 2010.
• Smeeton, J, Zhang, X, Bulus, N, Mernaugh, G, Lange, A, Karner, CM, Carroll, TJ, Fässler, R, Pozzi, A, Rosenblum, ND, Zent, R Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development. Development, 137(19), 3233-43, 2010.
• Riggins, KS, Mernaugh, G, Su, Y, Quaranta, V, Koshikawa, N, Seiki, M, Pozzi, A, Zent, R MT1-MMP-mediated basement membrane remodeling modulates renal development. Exp Cell Res, 316(17), 2993-3005, 2010.
• Wang, SE, Yu, Y, Criswell, TL, Debusk, LM, Lin, PC, Zent, R, Johnson, DH, Ren, X, Arteaga, CL Oncogenic mutations regulate tumor microenvironment through induction of growth factors and angiogenic mediators. Oncogene, 2010.
• Pozzi, A, Zent, R Regulation of endothelial cell functions by basement membrane- and arachidonic acid-derived products. Wiley Interdiscip Rev Syst Biol Med, 1(2), 254-72, 2010.
• He, W, Wang, Y, Zhang, MZ, You, L, Davis, LS, Fan, H, Yang, HC, Fogo, AB, Zent, R, Harris, RC, Breyer, MD, Hao, CM Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest, 120(4), 1056-68, 2010.
• Gewin, L, Bulus, N, Mernaugh, G, Moeckel, G, Harris, RC, Moses, HL, Pozzi, A, Zent, R TGF-beta receptor deletion in the renal collecting system exacerbates fibrosis. J Am Soc Nephrol, 21(8), 1334-43, 2010.
• Clark, PE, Polosukhina, DA, Gyabaah, K, Moses, HL, Thorburn, A, Zent, R TRAIL and interferon-alpha act synergistically to induce renal cell carcinoma apoptosis. J Urol, 184(3), 1166-74, 2010.
• Yamashita, H, Tripathi, M, Harris, MP, Liu, S, Weidow, B, Zent, R, Quaranta, V The role of a recombinant fragment of laminin-332 in integrin alpha3beta1-dependent cell binding, spreading and migration. Biomaterials, 31(19), 5110-21, 2010.
• Pozzi, A, Zent, R ZO-1 and ZONAB interact to regulate proximal tubular cell differentiation. J Am Soc Nephrol, 21(3), 388-90, 2010.
• Cheng, H, Fan, X, Guan, Y, Moeckel, GW, Zent, R, Harris, RC Distinct roles for basal and induced COX-2 in podocyte injury. J Am Soc Nephrol, 20(9), 1953-62, 2009.
• Lange, A, Wickström, SA, Jakobson, M, Zent, R, Sainio, K, Fässler, R Integrin-linked kinase is an adaptor with essential functions during mouse development. Nature, 461(7266), 1002-6, 2009.
• 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, 20(10), 2119-25, 2009.
• Pozzi, A, Voziyan, PA, Hudson, BG, Zent, R Regulation of matrix synthesis, remodeling and accumulation in glomerulosclerosis. Curr Pharm Des, 15(12), 1318-33, 2009.
• Nyström, A, Shaik, ZP, Gullberg, D, Krieg, T, Eckes, B, Zent, R, Pozzi, A, Iozzo, RV Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity. Blood, 114(23), 4897-906, 2009.
• Benjamin, JT, Gaston, DC, Halloran, BA, Schnapp, LM, Zent, R, Prince, LS The role of integrin alpha8beta1 in fetal lung morphogenesis and injury. Dev Biol, 335(2), 407-17, 2009.
• Moser, M, Legate, KR, Zent, R, Fässler, R The tail of integrins, talin, and kindlins. Science, 324(5929), 895-9, 2009.
• Moser M, Legate KR, Zent R, Fassler R. "The tail of integrins, talin, and kindlins.." Science, 15(324), 895-9, 2009.
• Wang, SE, Xiang, B, Zent, R, Quaranta, V, Pozzi, A, Arteaga, CL Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton. Cancer Res, 69(2), 475-82, 2009.
• Zhang, X, Mernaugh, G, Yang, DH, Gewin, L, Srichai, MB, Harris, RC, Iturregui, JM, Nelson, RD, Kohan, DE, Abrahamson, D, Fässler, R, Yurchenco, P, Pozzi, A, Zent, R beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity. Development, 136(19), 3357-66, 2009.
• Srichai, MB, Hao, C, Davis, L, Golovin, A, Zhao, M, Moeckel, G, Dunn, S, Bulus, N, Harris, RC, Zent, R, Breyer, MD Apoptosis of the Thick Ascending Limb Results in Acute Kidney Injury. J Am Soc Nephrol, 2008.
• Pozzi, A, Jarad, G, Moeckel, GW, Coffa, S, Zhang, X, Gewin, L, Eremina, V, Hudson, BG, Borza, DB, Harris, RC, Holzman, LB, Phillips, CL, Fassler, R, Quaggin, SE, Miner, JH, Zent, R Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol, 316(2), 288-301, 2008.
• Abair, TD, Sundaramoorthy, M, Chen, D, Heino, J, Ivaska, J, Hudson, BG, Sanders, CR, Pozzi, A, Zent, R Cross-talk between integrins alpha1beta1 and alpha2beta1 in renal epithelial cells. Exp Cell Res, 314(19), 3593-604, 2008.
• Abair, TD, Bulus, N, Borza, C, Sundaramoorthy, M, Zent, R, Pozzi, A Functional Analysis of the cytoplasmic domain of the integrin {alpha}1 subunit in endothelial cells. Blood, 2008.
• Borza, CM, Borza, DB, Pedchenko, V, Saleem, MA, Mathieson, PW, Sado, Y, Hudson, HM, Pozzi, A, Saus, J, Abrahamson, DR, Zent, R, Hudson, BG Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 collagen IV network. J Am Soc Nephrol, 19(4), 677-84, 2008.
• Montanez, E, Ussar, S, Schifferer, M, Bösl, M, Zent, R, Moser, M, Fässler, R Kindlin-2 controls bidirectional signaling of integrins. Genes Dev, 22(10), 1325-30, 2008.
• Macias-Perez, I, Borza, C, Chen, X, Yan, X, Ibanez, R, Mernaugh, G, Matrisian, LM, Zent, R, Pozzi, A Loss of integrin alpha1beta1 ameliorates Kras-induced lung cancer. Cancer Res, 68(15), 6127-35, 2008.
• Macias-Perez, IM, Zent, R, Carmosino, M, Breyer, MD, Breyer, RM, Pozzi, A Mouse EP3 alpha, beta, and gamma receptor variants reduce tumor cell proliferation and tumorigenesis in vivo. J Biol Chem, 283(18), 12538-45, 2008.
• Maginnis, MS, Mainou, BA, Derdowski, A, Johnson, EM, Zent, R, Dermody, TS NPXY motifs in the beta1 integrin cytoplasmic tail are required for functional reovirus entry. J Virol, 82(7), 3181-91, 2008.
• Erdogan, M, Pozzi, A, Bhowmick, N, Moses, HL, Zent, R Transforming growth factor-beta (TGF-beta) and TGF-beta-associated kinase 1 are required for R-Ras-mediated transformation of mammary epithelial cells. Cancer Res, 68(15), 6224-31, 2008.
• Zent, R, Pozzi, A Angiogenesis in diabetic nephropathy. Semin Nephrol, 27(2), 161-71, 2007.
• Dwyer, JP, Yates, KM, Sumner, EL, Stone, WJ, Wang, Y, Koury, MJ, Fogo, AB, Zent, R Chronic myeloid leukemia-associated membranoproliferative glomerulonephritis that responded to imatinib mesylate therapy. Clin Nephrol, 67(3), 176-81, 2007.
• Zeng, F, Zhang, MZ, Singh, AB, Zent, R, Harris, RC ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis. Mol Biol Cell, 18(11), 4446-56, 2007.
• Chen, X, Abair, TD, Ibanez, MR, Su, Y, Frey, MR, Dise, RS, Polk, DB, Singh, AB, Harris, RC, Zent, R, Pozzi, A Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation. Mol Cell Biol, 27(9), 3313-26, 2007.
• Voss, B, McLaughlin, JN, Holinstat, M, Zent, R, Hamm, HE PAR1, but not PAR4, activates human platelets through a Gi/o/phosphoinositide-3 kinase signaling axis. Mol Pharmacol, 71(5), 1399-406, 2007.
• Rao, R, Redha, R, Macias-Perez, I, Su, Y, Hao, C, Zent, R, Breyer, MD, Pozzi, A Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem, 282(23), 16959-68, 2007.
• Erdogan, M, Pozzi, A, Bhowmick, N, Moses, HL, Zent, R Signaling pathways regulating TC21-induced tumorigenesis. J Biol Chem, 282(38), 27713-20, 2007.
• Liang, XB, Ma, LJ, Naito, T, Wang, Y, Madaio, M, Zent, R, Pozzi, A, Fogo, AB Angiotensin type 1 receptor blocker restores podocyte potential to promote glomerular endothelial cell growth. J Am Soc Nephrol, 17(7), 1886-95, 2006.
• Zent, R, Pozzi, A Antiangiogenic therapy in diabetic nephropathy. J Am Soc Nephrol, 17(2), 325-7, 2006.
• 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, 70(3), 460-70, 2006.
• Pozzi, A, Coffa, S, Bulus, N, Zhu, W, Chen, D, Chen, X, Mernaugh, G, Su, Y, Cai, S, Singh, A, Brissova, M, Zent, R H-Ras, R-Ras, and TC21 Differentially Regulate Ureteric Bud Cell Branching Morphogenesis. Mol Biol Cell, 2006.
• Borza, CM, Pozzi, A, Borza, DB, Pedchenko, V, Hellmark, T, Hudson, BG, Zent, R Integrin {alpha}3beta1, a Novel Receptor for {alpha}3(IV) Noncollagenous Domain and a Trans-dominant Inhibitor for Integrin {alpha}vbeta3. J Biol Chem, 281(30), 20932-9, 2006.
• Moeckel, GW, Zhang, L, Chen, X, Rossini, M, Zent, R, Pozzi, A Role of integrin alpha1beta1 in the regulation of renal medullary osmolyte concentration. Am J Physiol Renal Physiol, 290(1), F223-31, 2006.
• Nakagawa, K, Holla, VR, Wei, Y, Wang, WH, Gatica, A, Wei, S, Mei, S, Miller, CM, Cha, DR, Price, E, Zent, R, Pozzi, A, Breyer, MD, Guan, Y, Falck, JR, Waterman, MR, Capdevila, JH Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel. J Clin Invest, 116(6), 1696-702, 2006.
• Muraoka-Cook, RS, Shin, I, Yi, JY, Easterly, E, Barcellos-Hoff, MH, Yingling, JM, Zent, R, Arteaga, CL Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene, 2005.
• Chen, X, Su, Y, Fingleton, B, Acuff, H, Matrisian, LM, Zent, R, Pozzi, A An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth in integrin alpha1-null mice. Clin Exp Metastasis, 22(2), 185-93, 2005.
• Cai, S, Bulus, N, Fonseca-Siesser, PM, Chen, D, Hanks, SK, Pozzi, A, Zent, R CD98 modulates integrin beta1 function in polarized epithelial cells. J Cell Sci, 118(Pt 5), 889-99, 2005.
• Pozzi, A, Macias-Perez, I, Abair, T, Wey, S, Su, Y, Zent, R, Falk, JR, Capdevila, JH Charaterization of 5,6-and 8,9-Epoxyeicosatrienoic acids (5,6- AND 8,9-EET) as potent in vivo angiogenic lipids. J Biol Chem, 2005.
• Chen, X, Su, Y, Fingleton, B, Acuff, H, Matrisian, LM, Zent, R, Pozzi, A Increased plasma MMP9 in integrin alpha1-null mice enhances lung metastasis of colon carcinoma cells. Int J Cancer, 116(1), 52-61, 2005.
• Mai, W, Chen, D, Ding, T, Kim, I, Park, S, Cho, SY, Chu, JS, Liang, D, Wang, N, Wu, D, Li, S, Zhao, P, Zent, R, Wu, G Inhibition of Pkhd1 Impairs Tubulomorphogenesis of Cultured IMCD Cells. Mol Biol Cell, 2005.
• Tvorogov, D, Wang, XJ, Zent, R, Carpenter, G Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion. J Cell Sci, 118(Pt 3), 601-10, 2005.
• Mernaugh, RL, Yan, H, Chen, D, Edl, J, Hanley, G, Pozzi, A, Zent, R Production and characterization of mouse ureteric bud cell-specific rat hybridoma antibodies utilizing subtractive immunization and high-throughput screening. J Immunol Methods, 306(1-2), 115-27, 2005.
• Fisher, ME, Rossini, M, Simmons, E, Harris, RC, Moeckel, G, Zent, R A woman with chronic hepatitis C infection and nephrotic syndrome who developed multiple renal lesions after interferon alfa therapy. Am J Kidney Dis, 44(3), 567-73, 2004.
• Henderson, NC, Collis, EA, Mackinnon, AC, Simpson, KJ, Haslett, C, Zent, R, Ginsberg, M, Sethi, T CD98hc (SLC3A2) interaction with beta 1 integrins is required for transformation. J Biol Chem, 279(52), 54731-41, 2004.
• Chen, Dong, Roberts, Richard, Pohl, Martin, Nigam, Sanjay, Kreidberg, Jordan, Wang, Zemin, Heino, Jyrki, Ivaska, Johanna, Coffa, Sergio, Harris, Raymond C., Pozzi, Ambra, Zent, Roy Differential expression of collagen and laminin binding integrins mediate ureteric bud and inner medullary collecting duct cell tubulogenesis. Am J Physiol Renal Physiol, 2004.
• Chen, X, Moeckel, G, Morrow, JD, Cosgrove, D, Harris, RC, Fogo, AB, Zent, R, Pozzi, A Lack of integrin alpha1beta1 leads to severe glomerulosclerosis after glomerular injury. Am J Pathol, 165(2), 617-30, 2004.
• Singh, Amar B, Tsukada, Toshiaki, Zent, Roy, Harris, Raymond C Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells. J Cell Sci, 117(Pt 8), 1365-79, 2004.
• Pedchenko, Vadim, Zent, Roy, Hudson, Billy G. {alpha}v{beta}3 and {alpha}v{beta}5 Integrins Bind Both the Proximal RGD Site and Non-RGD Motifs within Noncollagenous (NC1) Domain of the {alpha}3 Chain of Type IV Collagen: IMPLICATION FOR THE MECHANISM OF ENDOTHELIAL CELL ADHESION. J Biol Chem, 279(4), 2772-2780, 2004.
• Hata, Aaron N, Zent, Roy, Breyer, Matthew D, Breyer, Richard M Expression and molecular pharmacology of the mouse CRTH2 receptor. J Pharmacol Exp Ther, 306(2), 463-70, 2003.
• Pozzi, Ambra, Zent, Roy Integrins: sensors of extracellular matrix and modulators of cell function. Nephron Exp Nephrol, 94(3), e77-84, 2003.
• Koshikawa, Naohiko, Schenk, Susann, Moeckel, Gilbert, Sharabi, Andrew, Miyazaki, Kaoru, Gardner, Humphrey, Zent, Roy, Quaranta, Vito Proteolytic processing of laminin-5 by MT1-MMP in tissues and its effects on epithelial cell morphology. FASEB J, 2003.
• Fenczik, C A, Zent, R, Dellos, M, Calderwood, D A, Satriano, J, Kelly, C, Ginsberg, M H Distinct domains of CD98hc regulate integrins and amino acid transport. J Biol Chem, 276(12), 8746-52, 2001.
• Bhowmick, N A, Zent, R, Ghiassi, M, McDonnell, M, Moses, H L Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J Biol Chem, 276(50), 46707-13, 2001.
• Zent, R, Bush, K T, Pohl, M L, Quaranta, V, Koshikawa, N, Wang, Z, Kreidberg, J A, Sakurai, H, Stuart, R O, Nigám, S K Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development. Dev Biol, 238(2), 289-302, 2001.
• Zent, R, Fenczik, C A, Calderwood, D A, Liu, S, Dellos, M, Ginsberg, M H Class- and splice variant-specific association of CD98 with integrin beta cytoplasmic domains. J Biol Chem, 275(7), 5059-64, 2000.
• Zent, R, Ailenberg, M, Downey, G P, Silverman, M ROS stimulate reorganization of mesangial cell-collagen gels by tyrosine kinase signaling. Am J Physiol, 276(2 Pt 2), F278-87, 1999.
• Calderwood, D A, Zent, R, Grant, R, Rees, D J, Hynes, R O, Ginsberg, M H The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation. J Biol Chem, 274(40), 28071-4, 1999.
• Zent, R, Ailenberg, M, Silverman, M Tyrosine kinase cell signaling pathways of rat mesangial cells in 3-dimensional cultures: response to fetal bovine serum and platelet-derived growth factor-BB. Exp Cell Res, 240(1), 134-43, 1998.
• Zent, R, Nagai, R, Cattran, D C Idiopathic membranous nephropathy in the elderly: a comparative study. Am J Kidney Dis, 29(2), 200-6, 1997.
• Zent, R, Katz, A, Quaggin, S, Cattran, D, Wade, J, Cardella, C, Zaltzman, J, Fenton, S, Cole, E Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A. Clin Nephrol, 47(3), 181-6, 1997.
• De Villiers, C, Zent, R, Eastman, R W, Swingler, D A flight of fantasy: false memories in frontal lobe disease. J Neurol Neurosurg Psychiatry, 61(6), 652-3, 1996.
• Zent, R, Ailenberg, M, Waddell, T K, Downey, G P, Silverman, M Puromycin aminonucleoside inhibits mesangial cell-induced contraction of collagen gels by stimulating production of reactive oxygen species. Kidney Int, 47(3), 811-7, 1995.
• Zent, R, Myers, J E, Donald, D, Rayner, B L Continuous ambulatory peritoneal dialysis: an option in the developing world. Perit Dial Int, 14(1), 48-51, 1994.
• Zent, R, Van Zyl Smit, R, Duffield, M, Cassidy, M J Crescentic nephritis at Groote Schuur Hospital, South Africa--not a benign disease. Clin Nephrol, 42(1), 22-9, 1994.
• Bargman, J M, Zent, R, Ellis, P, Auger, M, Wilson, S Diagnosis of lymphoma in a continuous ambulatory peritoneal dialysis patient by peritoneal fluid cytology. Am J Kidney Dis, 23(5), 747-50, 1994.
• Katz, A, Zent, R, Bargman, J M IgG heavy-chain deposition disease. Mod Pathol, 7(8), 874-8, 1994.
• Morton, L P, Reynolds, L, Zent, R, Rayner, B L Hearing thresholds in CAPD patients. Adv Perit Dial, 8150-2, 1992.

Education

• M.D. - University of the Witwatersrand
• Ph.D. - University of Toronto
• Fellowship - Toronto Western Hospital
• Internship - Johannesburg General Hospital
• Residency - Groote Schuur Hospital, South Africa