Ambra Pozzi, Ph.D.

Professor

ambra.pozzi@vanderbilt.edu
Faculty Appointments
Professor of Medicine Professor of Molecular Physiology and BiophysicsProfessor of Cancer Biology
Education
Ph.D., Experimental. Pathology, University of Florence, Florence
Office Address
B-3115 MCN
TN 2372
Research Description
<b>Our laboratory has established two major lines of research.</b>

<strong>To study the molecular mechanisms of kidney fibrosis, focusing on cell-matrix interactions and arachidonic acid-derived eicosanoids in kidney injury. </strong>
Cell-matrix interaction in kidney homeostasis: As progressive accumulation of extracellular matrix (ECM), mainly collagens, leads to fibrosis, our goal is to determine how interactions between ECM and cells via specific ECM receptors control ECM synthesis/remodeling in health and disease. Among the collagen receptors, we study integrins and discodin domain receptors (DDRs). We have identified integrin alpha1 beta1 as an anti-fibrotic integrin whose activation leads to downregulation of endogenous collagen synthesis and negatively modulates fibrosis. Recently, we have identified integrin alpha2 beta1 and DDR1 as a positive regulator of kidney fibrosis and provide evidence that mice lacking these receptors are protected from fibrosis following injury. Finally, we study how these matrix receptors crosstalk with pro-fibrotic growth factor receptors, including EGF and TGF-b receptors.

Arachidonic acid-derived eicosanoids in kidney homeostasis: The P450 arachidonic acid monooxygenases oxidize arachidonic acid to a) 19- or 20-HETE (w-hydroxylase or CYP4 isoforms), or b) 5,6-, 8,9-, 11,12-, or 14,15-EET (epoxygenase or CYP2 isoforms). Both EETs and HETEs have markedly divergent biological effects depending on the tissue of origin. For example, 20-HETE causes vasoconstriction and promotes hypertension, while EETs are vasodilators and lower blood pressure. As hypertension and kidney injury are frequently associated, a goal of our research is to determine the relative contribution of EETs vs. HETE to kidney homeostasis by using mice lacking and/or overexpressing key enzymes involved in the synthesis of EETs and/or HETEs. Using these in vivo tools we intend to test the hypothesis that EETs protects from, while 20-HETEs contributes to kidney injury.

<strong>To study the molecular mechanisms controlling endothelial cell functions in order to devise valid and better tolerated anti-angiogenic therapy.</strong>
In the past 10 years our laboratory has investigated the role of cell-matrix interaction in the control of endothelial cell functions in vivo and in vitro and provide the first evidence that the collagen binding integrin alpha1beta1 is pro-angiogenic and pro-tumorigenic and its inhibition and/or down-regulation is beneficial in the setting of tumor associated angiogenesis. More recently, we have started to investigate the role of arachidonic acid P450 epoxygenases in the control of endothelial cell function in vitro and tumorigenesis in vivo. We provide evidence that the products of P450 epoxygenases are pro-angiogenic <em>in vivo</em> and <em>in vitro</em> and maneuvers to prevent their synthesis plays a beneficial effect in slowing cancer progression <em>in vivo</em>.
Research Keywords
Role of arachidonic acid derived lipids in angiogenesis and tumorigenesis
Clinical Research Keywords
integrins, lipids, angiogenesis, tumorigenesis, diabetes
Publications
Irvin MW, Zijlstra A, Wikswo JP, Pozzi A. Techniques and assays for the study of angiogenesis. Exp. Biol. Med. (Maywood) [print-electronic]. 2014 Nov; 239(11): 1476-88. PMID: 24872440, PMCID: PMC4216737, PII: 1535370214529386, DOI: 10.1177/1535370214529386, ISSN: 1535-3699.

Miller CG, Pozzi A, Zent R, Schwarzbauer JE. Effects of high glucose on integrin activity and fibronectin matrix assembly by mesangial cells. Mol. Biol. Cell [print-electronic]. 2014 Aug 8/15/2014; 25(16): 2342-50. PMID: 24943838, PMCID: PMC4142608, PII: mbc.E14-03-0800, DOI: 10.1091/mbc.E14-03-0800, ISSN: 1939-4586.

Reinert RB, Cai Q, Hong JY, Plank JL, Aamodt K, Prasad N, Aramandla R, Dai C, Levy SE, Pozzi A, Labosky PA, Wright CV, Brissova M, Powers AC. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding. Development [print-electronic]. 2014 Apr; 141(7): 1480-91. PMID: 24574008, PMCID: PMC3957372, PII: dev.098657, DOI: 10.1242/dev.098657, ISSN: 1477-9129.

Parekh R, Lorenzo MK, Shin SY, Pozzi A, Clark AL. Integrin a1ß1 differentially regulates cytokine-mediated responses in chondrocytes. Osteoarthr. Cartil [print-electronic]. 2014 Mar; 22(3): 499-508. PMID: 24418674, PMCID: PMC4028170, PII: S1063-4584(14)00009-0, DOI: 10.1016/j.joca.2013.12.019, ISSN: 1522-9653.

Jablonski CL, Ferguson S, Pozzi A, Clark AL. Integrin a1ß1 participates in chondrocyte transduction of osmotic stress. Biochem. Biophys. Res. Commun [print-electronic]. 2014 Feb 2/28/2014; 445(1): 184-90. PMID: 24495803, PMCID: PMC4022045, PII: S0006-291X(14)00192-2, DOI: 10.1016/j.bbrc.2014.01.157, ISSN: 1090-2104.

Borza CM, Pozzi A. Discoidin domain receptors in disease. Matrix Biol [print-electronic]. 2014 Feb; 34: 185-92. PMID: 24361528, PMCID: PMC4019715, PII: S0945-053X(13)00170-4, DOI: 10.1016/j.matbio.2013.12.002, ISSN: 1569-1802.

Skrypnyk N, Chen X, Hu W, Su Y, Mont S, Yang S, Gangadhariah M, Wei S, Falck JR, Jat JL, Zent R, Capdevila JH, Pozzi A. PPARa activation can help prevent and treat non-small cell lung cancer. Cancer Res [print-electronic]. 2014 Jan 1/15/2014; 74(2): 621-31. PMID: 24302581, PMCID: PMC3902646, PII: 0008-5472.CAN-13-1928, DOI: 10.1158/0008-5472.CAN-13-1928, ISSN: 1538-7445.

Jiang L, Yang S, Yin H, Fan X, Wang S, Yao B, Pozzi A, Chen X, Harris RC, Zhang MZ. Epithelial-specific deletion of 11ß-HSD2 hinders Apcmin/+ mouse tumorigenesis. Mol. Cancer Res [print-electronic]. 2013 Sep; 11(9): 1040-50. PMID: 23741059, PMCID: PMC3778073, PII: 1541-7786.MCR-13-0084-T, DOI: 10.1158/1541-7786.MCR-13-0084-T, ISSN: 1557-3125.

Pozzi A, Zent R. Integrins in kidney disease. J. Am. Soc. Nephrol [print-electronic]. 2013 Jun; 24(7): 1034-9. PMID: 23641054, PMCID: PMC3699832, PII: ASN.2013010012, DOI: 10.1681/ASN.2013010012, ISSN: 1533-3450.

Luo P, Dematteo A, Wang Z, Zhu L, Wang A, Kim HS, Pozzi A, Stafford JM, Luther JM. Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. Diabetologia [print-electronic]. 2013 Apr; 56(4): 901-10. PMID: 23314847, PMCID: PMC3593801, DOI: 10.1007/s00125-012-2814-8, ISSN: 1432-0428.

Gewin L, Vadivelu S, Neelisetty S, Srichai MB, Paueksakon P, Pozzi A, Harris RC, Zent R. Deleting the TGF-ß receptor attenuates acute proximal tubule injury. J. Am. Soc. Nephrol [print-electronic]. 2012 Dec; 23(12): 2001-11. PMID: 23160515, PMCID: PMC3507360, PII: ASN.2012020139, DOI: 10.1681/ASN.2012020139, ISSN: 1533-3450.

Mathew S, Lu Z, Palamuttam RJ, Mernaugh G, Hadziselimovic A, Chen J, Bulus N, Gewin LS, Voehler M, Meves A, Ballestrem C, Fässler R, Pozzi A, Sanders CR, Zent R. ß1 integrin NPXY motifs regulate kidney collecting-duct development and maintenance by induced-fit interactions with cytosolic proteins. Mol. Cell. Biol [print-electronic]. 2012 Oct; 32(20): 4080-91. PMID: 22869523, PMCID: PMC3457338, PII: MCB.00568-12, DOI: 10.1128/MCB.00568-12, ISSN: 1098-5549.

Carpenter G, Pozzi A. Cell responses to growth factors: the role of receptor tyrosine kinase intracellular domain fragments. Sci Signal. 2012 Sep 9/25/2012; 5(243): pe42. PMID: 23012654, PII: scisignal.2003526, DOI: 10.1126/scisignal.2003526, ISSN: 1937-9145.

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.

Yu L, Su Y, Paueksakon P, Cheng H, Chen X, Wang H, Harris RC, Zent R, Pozzi A. Integrin a1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy. Kidney Int [print-electronic]. 2012 Jun; 81(11): 1086-97. PMID: 22297672, PMCID: PMC3345314, PII: ki2011474, DOI: 10.1038/ki.2011.474, ISSN: 1523-1755.

Mathew S, Chen X, Pozzi A, Zent R. Integrins in renal development. Pediatr. Nephrol [print-electronic]. 2012 Jun; 27(6): 891-900. PMID: 21603909, DOI: 10.1007/s00467-011-1890-1, ISSN: 1432-198X.

Borza CM, Pozzi A. The role of cell-extracellular matrix interactions in glomerular injury. Exp. Cell Res [print-electronic]. 2012 May 5/15/2012; 318(9): 1001-10. PMID: 22417893, PMCID: PMC3770307, PII: S0014-4827(12)00109-7, DOI: 10.1016/j.yexcr.2012.02.033, ISSN: 1090-2422.

Bulus N, Feral C, Pozzi A, Zent R. CD98 increases renal epithelial cell proliferation by activating MAPKs. PLoS ONE [print-electronic]. 2012; 7(6): e40026. PMID: 22768207, PMCID: PMC3386947, PII: PONE-D-11-23182, DOI: 10.1371/journal.pone.0040026, ISSN: 1932-6203.

Pozzi A, Zent R. Hold tight or you'll fall off: CD151 helps podocytes stick in high-pressure situations. J. Clin. Invest [print-electronic]. 2012 Jan; 122(1): 13-6. PMID: 22201676, PMCID: PMC3248315, PII: 61858, DOI: 10.1172/JCI61858, ISSN: 1558-8238.

Schneider C, Pozzi A. Cyclooxygenases and lipoxygenases in cancer. Cancer Metastasis Rev. 2011 Dec; 30(3-4): 277-94. PMID: 22002716, PMCID: PMC3798028, DOI: 10.1007/s10555-011-9310-3, ISSN: 1573-7233.

Pozzi A, Zent R. Extracellular matrix receptors in branched organs. Curr. Opin. Cell Biol [print-electronic]. 2011 Oct; 23(5): 547-53. PMID: 21561755, PMCID: PMC3181278, PII: S0955-0674(11)00051-2, DOI: 10.1016/j.ceb.2011.04.003, ISSN: 1879-0410.

Li B, Pozzi A, Young PP. TNFalpha accelerates monocyte to endothelial transdifferentiation in tumors by the induction of integrin alpha5 expression and adhesion to fibronectin. Mol. Cancer Res [print-electronic]. 2011 Jun; 9(6): 702-11. PMID: 21536688, PMCID: PMC3157289, PII: 1541-7786.MCR-10-0484, DOI: 10.1158/1541-7786.MCR-10-0484, ISSN: 1557-3125.

Griesser M, Suzuki T, Tejera N, Mont S, Boeglin WE, Pozzi A, Schneider C. Biosynthesis of hemiketal eicosanoids by cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2011 Apr 4/26/2011; 108(17): 6945-50. PMID: 21482803, PMCID: PMC3084063, PII: 1019473108, DOI: 10.1073/pnas.1019473108, ISSN: 1091-6490.

Pozzi A, Zent R. TGF-ß sequestration by mesangial cell integrin avß8: A novel mechanism of glomerular endothelial cell regulation. Am. J. Pathol. 2011 Feb; 178(2): 485-9. PMID: 21281780, PMCID: PMC3069894, PII: S0002-9440(10)00134-3, DOI: 10.1016/j.ajpath.2010.10.038, ISSN: 1525-2191.

Kang L, Ayala JE, Lee-Young RS, Zhang Z, James FD, Neufer PD, Pozzi A, Zutter MM, Wasserman DH. Diet-induced muscle insulin resistance is associated with extracellular matrix remodeling and interaction with integrin alpha2beta1 in mice. Diabetes. 2011 Feb; 60(2): 416-26. PMID: 21270253, PMCID: PMC3028340, PII: 60/2/416, DOI: 10.2337/db10-1116, ISSN: 1939-327X.

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 [print-electronic]. 2010 Dec 12/17/2010; 285(51): 40114-24. PMID: 20940300, PMCID: PMC3000994, PII: M110.156729, DOI: 10.1074/jbc.M110.156729, ISSN: 1083-351X.

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 [print-electronic]. 2010 Oct 10/15/2010; 316(17): 2993-3005. PMID: 20727881, PMCID: PMC2945451, PII: S0014-4827(10)00397-6, DOI: 10.1016/j.yexcr.2010.08.003, ISSN: 1090-2422.

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 [print-electronic]. 2010 Aug; 21(8): 1334-43. PMID: 20576806, PMCID: PMC2938601, PII: ASN.2010020147, DOI: 10.1681/ASN.2010020147, ISSN: 1533-3450.

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 [print-electronic]. 2010 Jun; 30(12): 3048-58. PMID: 20368353, PMCID: PMC2876688, PII: MCB.00892-09, DOI: 10.1128/MCB.00892-09, ISSN: 1098-5549.

Pozzi A, Popescu V, Yang S, Mei S, Shi M, Puolitaival SM, Caprioli RM, Capdevila JH. The anti-tumorigenic properties of peroxisomal proliferator-activated receptor alpha are arachidonic acid epoxygenase-mediated. J. Biol. Chem [print-electronic]. 2010 Apr 4/23/2010; 285(17): 12840-50. PMID: 20178979, PMCID: PMC2857132, PII: M109.081554, DOI: 10.1074/jbc.M109.081554, ISSN: 1083-351X.

Gewin L, Bulus N, Mernaugh G, Moeckel G, Harris RC, Moses HL, Pozzi A, Zent R.. TGF-β Receptor Deletion in the Renal Collecting System Exacerbates Fibrosis. J. A. Soc. Neph. 2010; ((Jun 24. [Epub ahead of print])).

Turner J, Sazonova O, Wang H, Pozzi A, Wagner GF.. Induction of the renal stanniocalcin-1 gene in rodents by water deprivation. Mol Cell Endocrinol. 2010; (([Epub ahead of print])).

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 [print-electronic]. 2009 Oct; 136(19): 3357-66. PMID: 19710172, PMCID: PMC2739149, PII: dev.036269, DOI: 10.1242/dev.036269, ISSN: 1477-9129.

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.

Yang S, Wei S, Pozzi A, Capdevila JH. The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis. Arch. Biochem. Biophys [print-electronic]. 2009 Sep; 489(1-2): 82-91. PMID: 19464254, PMCID: PMC3786555, PII: S0003-9861(09)00152-0, DOI: 10.1016/j.abb.2009.05.006, ISSN: 1096-0384.

Pozzi A, Zent R. Regulation of endothelial cell functions by basement membrane- and arachidonic acid-derived products. Wiley Interdiscip Rev Syst Biol Med. 2009 Sep; 1(2): 254-72. PMID: 20835995, PMCID: PMC3789245, DOI: 10.1002/wsbm.7, ISSN: 1939-005X.

Crooke CE, Pozzi A, Carpenter GF. PLC-gamma1 regulates fibronectin assembly and cell aggregation. Exp. Cell Res [print-electronic]. 2009 Aug 8/1/2009; 315(13): 2207-14. PMID: 19379731, PMCID: PMC2696586, PII: S0014-4827(09)00167-0, DOI: 10.1016/j.yexcr.2009.04.008, ISSN: 1090-2422.

Red Brewer M, Choi SH, Alvarado D, Moravcevic K, Pozzi A, Lemmon MA, Carpenter G. The juxtamembrane region of the EGF receptor functions as an activation domain. Mol. Cell. 2009 Jun 6/26/2009; 34(6): 641-51. PMID: 19560417, PMCID: PMC2719887, PII: S1097-2765(09)00388-8, DOI: 10.1016/j.molcel.2009.04.034, ISSN: 1097-4164.

Smith JP, Pozzi A, Dhawan P, Singh AB, Harris RC. Soluble HB-EGF induces epithelial-to-mesenchymal transition in inner medullary collecting duct cells by upregulating Snail-2. Am. J. Physiol. Renal Physiol [print-electronic]. 2009 May; 296(5): F957-65. PMID: 19244405, PMCID: PMC2681361, PII: 90490.2008, DOI: 10.1152/ajprenal.90490.2008, ISSN: 1931-857X.

Zhang MZ, Xu J, Yao B, Yin H, Cai Q, Shrubsole MJ, Chen X, Kon V, Zheng W, Pozzi A, Harris RC. Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J. Clin. Invest [print-electronic]. 2009 Apr; 119(4): 876-85. PMID: 19307727, PMCID: PMC2662561, PII: 37398, DOI: 10.1172/JCI37398, ISSN: 1558-8238.

Antar AA, Konopka JL, Campbell JA, Henry RA, Perdigoto AL, Carter BD, Pozzi A, Abel TW, Dermody TS. Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus. Cell Host Microbe. 2009 Jan 1/22/2009; 5(1): 59-71. PMID: 19154988, PMCID: PMC2642927, PII: S1931-3128(08)00398-3, DOI: 10.1016/j.chom.2008.12.001, ISSN: 1934-6069.

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.

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. 2009; 26;114(23):4897-906.

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 [print-electronic]. 2008 Nov 11/15/2008; 314(19): 3593-604. PMID: 18809396, PMCID: PMC2729514, PII: S0014-4827(08)00328-5, DOI: 10.1016/j.yexcr.2008.08.014, ISSN: 1090-2422.

Pyle AL, Atkinson JB, Pozzi A, Reese J, Eckes B, Davidson JM, Crimmins DL, Young PP. Regulation of the atheroma-enriched protein, SPRR3, in vascular smooth muscle cells through cyclic strain is dependent on integrin alpha1beta1/collagen interaction. Am. J. Pathol [print-electronic]. 2008 Nov; 173(5): 1577-88. PMID: 18832573, PMCID: PMC2570146, PII: S0002-9440(10)61542-8, DOI: 10.2353/ajpath.2008.080042, ISSN: 1525-2191.

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 [print-electronic]. 2008 Oct 10/15/2008; 112(8): 3242-54. PMID: 18647959, PMCID: PMC2569176, PII: blood-2007-12-126433, DOI: 10.1182/blood-2007-12-126433, ISSN: 1528-0020.

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 Aug 8/1/2008; 68(15): 6224-31. PMID: 18676846, PII: 68/15/6224, DOI: 10.1158/0008-5472.CAN-08-0513, ISSN: 1538-7445.

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 Aug 8/1/2008; 68(15): 6127-35. PMID: 18676835, PMCID: PMC2801028, PII: 68/15/6127, DOI: 10.1158/0008-5472.CAN-08-1395, ISSN: 1538-7445.

Pozzi A, Zent R. Integrins, extracellular matrix, and terminal differentiation of renal epithelial cells [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2008 Jun; 19(6): 1043-4. PMID: 18480310, PII: ASN.2008040370, DOI: 10.1681/ASN.2008040370, ISSN: 1533-3450.

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 [print-electronic]. 2008 May 5/2/2008; 283(18): 12538-45. PMID: 18230618, PMCID: PMC2335350, PII: M800105200, DOI: 10.1074/jbc.M800105200, ISSN: 0021-9258.

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 [print-electronic]. 2008 Apr 4/15/2008; 316(2): 288-301. PMID: 18328474, PMCID: PMC2396524, PII: S0012-1606(08)00039-0, DOI: 10.1016/j.ydbio.2008.01.022, ISSN: 1095-564X.

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 [print-electronic]. 2008 Apr; 19(4): 677-84. PMID: 18235087, PMCID: PMC2390958, PII: ASN.2007070793, DOI: 10.1681/ASN.2007070793, ISSN: 1533-3450.

Cosgrove D, Meehan DT, Delimont D, Pozzi A, Chen X, Rodgers KD, Tempero RM, Zallocchi M, Rao VH. Integrin alpha1beta1 regulates matrix metalloproteinases via P38 mitogen-activated protein kinase in mesangial cells: implications for Alport syndrome. Am. J. Pathol [print-electronic]. 2008 Mar; 172(3): 761-73. PMID: 18258846, PMCID: PMC2258247, PII: S0002-9440(10)61838-X, DOI: 10.2353/ajpath.2008.070473, ISSN: 0002-9440.

Zhang Z, Ramirez NE, Yankeelov TE, Li Z, Ford LE, Qi Y, Pozzi A, Zutter MM. Alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner. Blood [print-electronic]. 2008 Feb 2/15/2008; 111(4): 1980-8. PMID: 18042800, PMCID: PMC2234046, PII: blood-2007-06-094680, DOI: 10.1182/blood-2007-06-094680, ISSN: 0006-4971.

Woodall BP, Nyström A, Iozzo RA, Eble JA, Niland S, Krieg T, Eckes B, Pozzi A, Iozzo RV. Integrin alpha2beta1 is the required receptor for endorepellin angiostatic activity. J. Biol. Chem [print-electronic]. 2008 Jan 1/25/2008; 283(4): 2335-43. PMID: 18024432, PII: M708364200, DOI: 10.1074/jbc.M708364200, ISSN: 0021-9258.

Pozzi A, Capdevila JH. PPARalpha Ligands as Antitumorigenic and Antiangiogenic Agents. PPAR Res. 2008; 2008: 906542. PMID: 18725983, PMCID: PMC2517125, DOI: 10.1155/2008/906542, ISSN: 1687-4757.

Zhang H, Lawson WE, Polosukhin VV, Pozzi A, Blackwell TS, Litingtung Y, Chiang C. Inhibitor of differentiation 1 promotes endothelial survival in a bleomycin model of lung injury in mice. Am. J. Pathol [print-electronic]. 2007 Oct; 171(4): 1113-26. PMID: 17717145, PMCID: PMC1988863, PII: S0002-9440(10)62377-2, DOI: 10.2353/ajpath.2007.070226, ISSN: 0002-9440.

Erdogan M, Pozzi A, Bhowmick N, Moses HL, Zent R. Signaling pathways regulating TC21-induced tumorigenesis. J. Biol. Chem [print-electronic]. 2007 Sep 9/21/2007; 282(38): 27713-20. PMID: 17656362, PII: M703037200, DOI: 10.1074/jbc.M703037200, ISSN: 0021-9258.

Pozzi A, Ibanez MR, Gatica AE, Yang S, Wei S, Mei S, Falck JR, Capdevila JH. Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. J. Biol. Chem [print-electronic]. 2007 Jun 6/15/2007; 282(24): 17685-95. PMID: 17405874, PII: M701429200, DOI: 10.1074/jbc.M701429200, ISSN: 0021-9258.

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 [print-electronic]. 2007 Jun 6/8/2007; 282(23): 16959-68. PMID: 17401137, PII: M701214200, DOI: 10.1074/jbc.M701214200, ISSN: 0021-9258.

Kanjanabuch T, Ma LJ, Chen J, Pozzi A, Guan Y, Mundel P, Fogo AB. PPAR-gamma agonist protects podocytes from injury. Kidney Int [print-electronic]. 2007 Jun; 71(12): 1232-9. PMID: 17457378, PII: 5002248, DOI: 10.1038/sj.ki.5002248, ISSN: 0085-2538.

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 [print-electronic]. 2007 May; 27(9): 3313-26. PMID: 17339338, PMCID: PMC1899972, PII: MCB.01476-06, DOI: 10.1128/MCB.01476-06, ISSN: 0270-7306.

Zent R, Pozzi A. Angiogenesis in diabetic nephropathy. Semin. Nephrol. 2007 Mar; 27(2): 161-71. PMID: 17418685, PII: S0270-9295(07)00008-3, DOI: 10.1016/j.semnephrol.2007.01.007, ISSN: 0270-9295.

Kamiyama M, Pozzi A, Yang L, DeBusk LM, Breyer RM, Lin PC. EP2, a receptor for PGE2, regulates tumor angiogenesis through direct effects on endothelial cell motility and survival. Oncogene [print-electronic]. 2006 Nov 11/9/2006; 25(53): 7019-28. PMID: 16732324, PII: 1209694, DOI: 10.1038/sj.onc.1209694, ISSN: 0950-9232.

Muñoz NM, Upton M, Rojas A, Washington MK, Lin L, Chytil A, Sozmen EG, Madison BB, Pozzi A, Moon RT, Moses HL, Grady WM. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res. 2006 Oct 10/15/2006; 66(20): 9837-44. PMID: 17047044, PII: 66/20/9837, DOI: 10.1158/0008-5472.CAN-06-0890, ISSN: 0008-5472.

Acuff HB, Sinnamon M, Fingleton B, Boone B, Levy SE, Chen X, Pozzi A, Carbone DP, Schwartz DR, Moin K, Sloane BF, Matrisian LM. Analysis of host- and tumor-derived proteinases using a custom dual species microarray reveals a protective role for stromal matrix metalloproteinase-12 in non-small cell lung cancer. Cancer Res. 2006 Aug 8/15/2006; 66(16): 7968-75. PMID: 16912171, PII: 66/16/7968, DOI: 10.1158/0008-5472.CAN-05-4279, ISSN: 1538-7445.

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.

Borza CM, Pozzi A, Borza DB, Pedchenko V, Hellmark T, Hudson BG, Zent R. Integrin alpha3beta1, a novel receptor for alpha3(IV) noncollagenous domain and a trans-dominant Inhibitor for integrin alphavbeta3. J. Biol. Chem [print-electronic]. 2006 Jul 7/28/2006; 281(30): 20932-9. PMID: 16731529, PII: M601147200, DOI: 10.1074/jbc.M601147200, ISSN: 0021-9258.

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 [print-electronic]. 2006 Jul; 17(7): 1886-95. PMID: 16790514, PII: ASN.2005020205, DOI: 10.1681/ASN.2005020205, ISSN: 1046-6673.

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 [print-electronic]. 2006 Jun; 116(6): 1696-702. PMID: 16691295, PMCID: PMC1459070, DOI: 10.1172/JCI27546, ISSN: 0021-9738.

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 [print-electronic]. 2006 Apr; 17(4): 2046-56. PMID: 16467383, PMCID: PMC1415315, PII: E05-08-0800, DOI: 10.1091/mbc.E05-08-0800, ISSN: 1059-1524.

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 [print-electronic]. 2006 Jan; 290(1): F223-31. PMID: 16106035, PII: 00371.2004, DOI: 10.1152/ajprenal.00371.2004, ISSN: 1931-857X.

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 [print-electronic]. 2005 Nov 11/30/2005; 306(1-2): 115-27. PMID: 16212977, PII: S0022-1759(05)00257-7, DOI: 10.1016/j.jim.2005.08.006, ISSN: 0022-1759.

Frank DB, Abtahi A, Yamaguchi DJ, Manning S, Shyr Y, Pozzi A, Baldwin HS, Johnson JE, de Caestecker MP. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ. Res [print-electronic]. 2005 Sep 9/2/2005; 97(5): 496-504. PMID: 16100039, PII: 01.RES.0000181152.65534.07, DOI: 10.1161/01.RES.0000181152.65534.07, ISSN: 1524-4571.

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 Aug 8/10/2005; 116(1): 52-61. PMID: 15756690, DOI: 10.1002/ijc.20997, ISSN: 0020-7136.

Pozzi A, Macias-Perez I, Abair T, Wei S, Su Y, Zent R, Falck JR, Capdevila JH. Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids. J. Biol. Chem [print-electronic]. 2005 Jul 7/22/2005; 280(29): 27138-46. PMID: 15917237, PII: M501730200, DOI: 10.1074/jbc.M501730200, ISSN: 0021-9258.

Thomas EK, Nakamura M, Wienke D, Isacke CM, Pozzi A, Liang P. Endo180 binds to the C-terminal region of type I collagen. J. Biol. Chem [print-electronic]. 2005 Jun 6/17/2005; 280(24): 22596-605. PMID: 15817460, PII: M501155200, DOI: 10.1074/jbc.M501155200, ISSN: 0021-9258.

Brábek J, Constancio SS, Siesser PF, Shin NY, Pozzi A, Hanks SK. Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells. Mol. Cancer Res. 2005 Jun; 3(6): 307-15. PMID: 15972849, PII: 3/6/307, DOI: 10.1158/1541-7786.MCR-05-0015, ISSN: 1541-7786.

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 [print-electronic]. 2005 Mar 3/1/2005; 118(Pt 5): 889-99. PMID: 15713750, PII: jcs.01674, DOI: 10.1242/jcs.01674, ISSN: 0021-9533.

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(2): 185-93. PMID: 16086239, DOI: 10.1007/s10585-005-7453-8, ISSN: 0262-0898.

Chen, X, Su, Y, Fingleton, B, Acuff, H, Matrisian, LM, Zent, R, Pozzi, A. Orthotopic models of lung cancer to follow primary and metastatic NSCLC growth in integrin α1-null mice. Clin. Exp. Metastasis. 2005.

Chen D, Roberts R, Pohl M, Nigam S, Kreidberg J, Wang Z, Heino J, Ivaska J, Coffa S, Harris RC, Pozzi A, Zent R. Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis. Am. J. Physiol. Renal Physiol [print-electronic]. 2004 Oct; 287(4): F602-11. PMID: 15187002, PII: 00015.2004, DOI: 10.1152/ajprenal.00015.2004, ISSN: 1931-857X.

Brábek J, Constancio SS, Shin NY, Pozzi A, Weaver AM, Hanks SK. CAS promotes invasiveness of Src-transformed cells. Oncogene. 2004 Sep 9/23/2004; 23(44): 7406-15. PMID: 15273716, PII: 1207965, DOI: 10.1038/sj.onc.1207965, ISSN: 0950-9232.

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 Aug; 165(2): 617-30. PMID: 15277235, PMCID: PMC1618576, PII: S0002-9440(10)63326-3, ISSN: 0002-9440.

Pozzi A, Yan X, Macias-Perez I, Wei S, Hata AN, Breyer RM, Morrow JD, Capdevila JH. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J. Biol. Chem [print-electronic]. 2004 Jul 7/9/2004; 279(28): 29797-804. PMID: 15123663, PII: M313989200, DOI: 10.1074/jbc.M313989200, ISSN: 0021-9258.

Brantley-Sieders DM, Caughron J, Hicks D, Pozzi A, Ruiz JC, Chen J. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J. Cell. Sci [print-electronic]. 2004 Apr 4/15/2004; 117(Pt 10): 2037-49. PMID: 15054110, PII: jcs.01061, DOI: 10.1242/jcs.01061, ISSN: 0021-9533.

Ma LJ, Jha S, Ling H, Pozzi A, Ledbetter S, Fogo AB. Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats. Kidney Int. 2004 Jan; 65(1): 106-15. PMID: 14675041, DOI: 10.1111/j.1523-1755.2004.00381.x, ISSN: 0085-2538.

Moeckel GW, Zhang L, Fogo AB, Hao CM, Pozzi A, Breyer MD. COX2 activity promotes organic osmolyte accumulation and adaptation of renal medullary interstitial cells to hypertonic stress. J. Biol. Chem [print-electronic]. 2003 May 5/23/2003; 278(21): 19352-7. PMID: 12637551, PII: M302209200, DOI: 10.1074/jbc.M302209200, ISSN: 0021-9258.

Pozzi A, Zent R. Integrins: sensors of extracellular matrix and modulators of cell function. Nephron Exp. Nephrol. 2003; 94(3): e77-84. PMID: 12902617, PII: 72025, DOI: 72025, ISSN: 1660-2129.

Brantley DM, Cheng N, Thompson EJ, Lin Q, Brekken RA, Thorpe PE, Muraoka RS, Cerretti DP, Pozzi A, Jackson D, Lin C, Chen J. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002 Oct 10/10/2002; 21(46): 7011-26. PMID: 12370823, DOI: 10.1038/sj.onc.1205679, ISSN: 0950-9232.

Pozzi A, LeVine WF, Gardner HA. Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis. Oncogene. 2002 Jan 1/10/2002; 21(2): 272-81. PMID: 11803470, DOI: 10.1038/sj.onc.1205045, ISSN: 0950-9232.

Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA. Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization. 2000.

Rose D.M., A. Pozzi, and R. Zent. Integrins as Therapeutic targets. Emerging Therapeutic Target. 2000.

Giannelli G, Pozzi A, Stetler-Stevenson WG, Gardner HA, Quaranta V. Expression of matrix metalloprotease-2-cleaved laminin-5 in breast remodeling stimulated by sex steroids. 1999.

Gardner H, Broberg A, Pozzi A, Laato M, Heino J. Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis. 1999.

Pozzi A, Wary KK, Giancotti FG, Gardner HA. Integrin alpha1beta1 mediates a unique collagen- dependent proliferation pathway in vivo. 1998.

Pozzi A, Risek B, Kiang DT, Gilula NB, Kumar NM. Analysis of multiple gap junction gene products in the rodent and human mammary gland. 1995.

Available Postdoctoral Position Details