Center for Matrix Biology - Vanderbilt University and Medical Center

Roy Zent, Ph.D., M.D.
Associate Professor in the Department of Medicine

	Office Address:	C-3210 MCN
	Mailing Address:	C-3210 MCN Nashville, TN 2372
	Lab address:	MCN-C3210
	Phone:	322-4632
		email

Secondary appointment in the Cancer Biology department.
Secondary appointment in the Cell and Developmental Biology department.

Research Summary

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 as well as cell biology and whole organ culture to understand the basic mechanisms whereby integrin-ECM interactions modify epithelial cell function.

We primarily focus on the role of cell-ECM interactions and metallopproteinases in renal branching morphogenesis as well as how integrins determine the localization of transporters in epithelial cell structures. Branching morphogenesis is studied primarily in the context of renal development, specifically the development of the ureteric bud derived structures. We make use of a number of knockout animals of integrins and MMPs to study the functions of the molecules.

The project in which we are trying to determine how integrins control the localization of proteins associated with transport is based on a protein called CD98. This transmembrane protein interacts with integrins as well as with amino acid transporters and we are trying to determine the mechanisms whereby integrins regulate CD98-dependent amino acid transport.

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Associated initiative(s):

Angiogenesis

Diabetic Complications

Career opportunities:
None currently available

Selected Publications

» Moser M, Legate KR, Zent R, Fassler R. The tail of integrins, talin, and kindlins. Science 2009. 15:895-9

» Pozzi, A, Voziyan, PA, Hudson, BG, Zent, R Regulation of matrix synthesis, remodeling and accumulation in glomerulosclerosis Curr Pharm Des 2009. 15:1318-33

» 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 2008. 68:6127-35

» 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 2008. 19:677-84

» 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 2008. 316:288-301

» 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 2008. 283:12538-45

» 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 2008. 82:3181-91

» 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. :

» 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 2008. 68:6224-31

» 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 2008. 314:3593-604

» Erdogan, M, Pozzi, A, Bhowmick, N, Moses, HL, Zent, R Signaling pathways regulating TC21-induced tumorigenesis J Biol Chem 2007. 282:27713-20

» 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 2007. 282:16959-68

» Zent, R, Pozzi, A Angiogenesis in diabetic nephropathy Semin Nephrol 2007. 27:161-71

» 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 2007. 71:1399-406

» 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 2007. 67:176-81

» 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 2007. 18:4446-56

» 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 2007. 27:3313-26

» 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 2006. 290:F223-31

» 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 2006. 17:1886-95

» 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. :

» Zent, R, Pozzi, A Antiangiogenic therapy in diabetic nephropathy J Am Soc Nephrol 2006. 17:325-7

» 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 2006. 70:460-70

» 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 2006. 281:20932-9

» 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 2006. 116:1696-702

» 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 2005. 116:52-61

» Tvorogov, D, Wang, XJ, Zent, R, Carpenter, G Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion J Cell Sci 2005. 118:601-10

» 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 2005. 118:889-99

» 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 2005. 22:185-93

» 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. :

» 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 2005. 306:115-27

» 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. :

» 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. :

» 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 2004. 279:54731-41

» 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 2004. 279:2772-2780

» 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 2004. 117:1365-79

» 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 2004. 165:617-30

» 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 2004. 44:567-73

» 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. :

» Pozzi, Ambra, Zent, Roy Integrins: sensors of extracellular matrix and modulators of cell function Nephron Exp Nephrol 2003. 94:e77-84

» 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. :

» Hata, Aaron N, Zent, Roy, Breyer, Matthew D, Breyer, Richard M Expression and molecular pharmacology of the mouse CRTH2 receptor J Pharmacol Exp Ther 2003. 306:463-70

» Zent, R, Bush, K T, Pohl, M L, Quaranta, V, Koshikawa, N, Wang, Z, Kreidberg, J A, Sakurai, H, Stuart, R O, Nig?!m, S K Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development Dev Biol 2001. 238:289-302

» 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 2001. 276:46707-13

» 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 2001. 276:8746-52

» 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 2000. 275:5059-64

» 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 1999. 274:28071-4

» Zent, R, Ailenberg, M, Downey, G P, Silverman, M ROS stimulate reorganization of mesangial cell-collagen gels by tyrosine kinase signaling Am J Physiol 1999. 276:F278-87

» 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 1998. 240:134-43

» Zent, R, Nagai, R, Cattran, D C Idiopathic membranous nephropathy in the elderly: a comparative study Am J Kidney Dis 1997. 29:200-6

» 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 1997. 47:181-6

» De Villiers, C, Zent, R, Eastman, R W, Swingler, D A flight of fantasy: false memories in frontal lobe disease J Neurol Neurosurg Psychiatry 1996. 61:652-3

» 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 1995. 47:811-7

» Zent, R, Myers, J E, Donald, D, Rayner, B L Continuous ambulatory peritoneal dialysis: an option in the developing world Perit Dial Int 1994. 14:48-51

» 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 1994. 42:22-9

» Katz, A, Zent, R, Bargman, J M IgG heavy-chain deposition disease Mod Pathol 1994. 7:874-8

» 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 1994. 23:747-50

» Morton, L P, Reynolds, L, Zent, R, Rayner, B L Hearing thresholds in CAPD patients Adv Perit Dial 1992. 8:150-2