Roy Zent : Vanderbilt-Ingram Cancer Center

The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers

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 Specialty

Basic mechanisms of cell-extracellular matrix interactions.

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

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.
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.
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.
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, WickstrÃ¶m, SA, Jakobson, M, Zent, R, Sainio, K, FÃ¤ssler, 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.
NystrÃ¶m, 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, FÃ¤ssler, 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, FÃ¤ssler, 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, BÃ¶sl, M, Zent, R, Moser, M, FÃ¤ssler, 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, NigÃ¡m, 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.

Vanderbilt-Ingram Cancer Center