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Dorin Bogdan Borza

Vanderbilt University Medical Center, Nashville, USA

Institution web page: https://medschool.mc.vanderbilt.edu/facultydata/php_files/part_dept/show_part.php?id3=10748
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Born: 1968

Interests: type IV collagen, autoimmunity, autoantibodies, basement membranes, Goodpasture disease, anti-GBM nephritis, Alport syndrome, hereditary nephritis

Details:
My lab studies the pathogenesis of inherited and acquired diseases involving type IV collagen, a major component of all basement membranes. In particular, the alpha3alpha4alpha5(IV) collagen network of the glomerular basement membrane (GBM) is centrally implicated in the pathogenesis of various forms of hereditary nephritis, including Alport syndrome, and is also the target of pathogenic auto-antibodies or allo-antibodies in anti-GBM antibody disease. The long-term objectives of our research are to elucidate the molecular mechanisms underlying the pathogenesis of these diseases in human patients and mouse models.

Selected publications:
• Luo W, Wang XP, Kashtan CE, Borza DB. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic alpha3(IV) collagen autoepitopes in vivo. J Immunol, 185, p. 3520, 2010.
• 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, 363, p. 343, 2010.
• Summers SA, Steinmetz OM, Li M, Kausman JY, Semple T, Edgtton KL, Borza DB, Braley H, Holdsworth SR, Kitching AR. Th1 and Th17 cells induce proliferative glomerulonephritis. J Am Soc Nephrol, 20, p. 2518, 2009.
• Abrahamson DR, Hudson BG, Stroganova L, Borza DB, St John PL. Cellular origins of type IV collagen networks in developing glomeruli. J Am Soc Nephrol, 20, p. 1471, 2009.
• Gross O, Borza DB, Anders HJ, Licht C, Weber M, Segerer S, Torra R, Gubler MC, Heidet L, Harvey S, Cosgrove D, Lees G, Kashtan C, Gregory M, Savige J, Ding J, Thorner P, Abrahamson DR, Antignac C, Tryggvason K, Hudson B, Miner JH. Stem cell therapy for Alport syndrome: the hope beyond the hype. Nephrol Dial Transplant, 24, p. 731, 2009.
• 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, pp. 677-84, 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, pp. 288-301, 2008.
• Vanacore RM, Ham AJ, Cartailler JP, Sundaramoorthy M, Todd P, Pedchenko V, Sado Y, Borza DB, Hudson BG. A role for collagen IV cross-links in conferring immune privilege to the Goodpasture autoantigen: structural basis for the crypticity of B cell epitopes. J Biol Chem, 283, pp. 22737-48, 2008.
• Ho J, Gibson IW, Zacharias J, Fervenza F, Colon S, Borza DB. Antigenic heterogeneity of IgA anti-GBM disease: new renal targets of IgA autoantibodies. Am J Kidney Dis, 52, pp. 761-5, 2008.
• Kang JS, Colon S, Hellmark T, Sado Y, Hudson BG, Borza DB. Identification of noncollagenous sites encoding specific interactions and quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen: implications for Alport gene therapy. J Biol Chem. , 283(50), pp. 35070-7, 2008.
• Cosgrove D, Kalluri R, Miner JH, Segal Y, Borza DB. Choosing a mouse model to study the molecular pathobiology of Alport glomerulonephritis. Kidney Int, 71, pp. 615-8, 2007.
• Kang JS, Kashtan CE, Turner AN, Heidet L, Hudson BG, Borza DB. The alloantigenic sites of alpha3alpha4alpha5(IV) collagen: pathogenic X-linked alport alloantibodies target two accessible conformational epitopes in the alpha5NC1 domain. . J Biol Chem, 282, pp. 10670-7, 2007.
• Fox MA, Sanes JR, Borza DB, Eswarakumar VP, Fässler R, Hudson BG, John SW, Ninomiya Y, Pedchenko V, Pfaff SL, Rheault MN, Sado Y, Segal Y, Werle MJ, Umemori H. Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals. Cell, 129, pp. 179-93, 2007.
• Borza DB. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis. Nephron Exp Nephrol, 106, pp. e37-43, 2007.
• Kang JS, Wang XP, Miner JH, Morello R, Sado Y, Abrahamson DR, Borza DB. Loss of alpha3/alpha4(IV) collagen from the glomerular basement membrane induces a strain-dependent isoform switch to alpha5alpha6(IV) collagen associated with longer renal survival in Col4a3-/- Alport mice. J Am Soc Nephrol, 17, pp. 1962-9, 2006.
• Borza DB, Bondar O, Colon S, Todd P, Sado Y, Neilson EG, Hudson BG. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis. . J Biol Chem, 280, pp. 27147-54, 2005.
• Wang XP, Fogo AB, Colon S, Giannico G, Abul-Ezz SR, Miner JH, Borza DB. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. J Am Soc Nephrol, 16, pp. 3563-71, 2005.


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