.

Department of Pathology, Microbiology, and Immunology

 

 

   Dorin-Bogdan Borza, Ph.D.

 

 

Assistant Professor

Department of Medicine

Department of Pathology, Microbiology and Immunology

 

  Contact Information

 

 

Office Location:

MCN B-3109A

Phone: 615-322-4470

Fax: 615-343-7156

E-mail: Dorin-Bogdan.Borza@vanderbilt.edu

 

Campus Mail address:

  Dept. of Nephrology

  MCN S-3223 (2372)

 

US Mailing address:

Vanderbilt University School of Medicine 

Nephrology

MCN S-3223

Nashville, TN 37232-2372 

 

 

Education

 

 

postdoc, Univ of Kansas Medical Ctr, Kansas City, KS
Ph.D., University of Missouri-Kansas City, MO
M.Sc., University of Bucharest, Romania

 

 

Research Keywords

 

 

type IV collagen, autoimmunity, autoantibodies, glomerular basement membrane (GBM), Goodpasture disease, anti-GBM nephritis, Alport syndrome, hereditary nephritis, mouse models, glomerulonephritis, membranous nephropathy, Fcgamma receptors, complement

 

 

Research Description

 

 

Research in my lab is currently focused on pathogenic mechanisms of autoimmune glomerulonephritis and the structure, function and pathobiology of the glomerular basement membrane (GBM). Areas of interest include:
* Goodpasture (GP) disease/anti-GBM antibody nephritis;
* Alport post-transplant nephritis (APTN);
* mouse models of GP/anti-GBM disease and APTN;
* Alport syndrome and Alport mouse models;
* pathobiology of type IV collagen;
* murine membranous nephropathy (mechanisms and targeted therapies);
* role of IgG Fc receptors and complement in the pathobiology of autoantibody-mediated autoimmune diseases
* novel therapies for antibody-mediated glomerulonephritis;

 

 

Clinical Research Description

 

 

Not applicable

 

 

Publications

 

 

Olaru, F, Luo, W, Wang, XP, Ge, L, Hertz, JM, Kashtan, CE, Sado, Y, Segal, Y, Hudson, BG, Borza, DB. Quaternary epitopes of alpha345(IV) collagen initiate alport post-transplant anti-GBM nephritis. J Am Soc Nephrol, 24(6), 889-95, 2013

Olaru, F, Wang, XP, Luo, W, Ge, L, Miner, JH, Kleinau, S, Geiger, XJ, Wasiluk, A, Heidet, L, Kitching, AR, Borza, DB. Proteolysis Breaks Tolerance Toward Intact alpha345(IV) Collagen, Eliciting Novel Anti-Glomerular Basement Membrane Autoantibodies Specific for alpha345NC1 Hexamers. J Immunol, 190(4), 889-895, 2013

Borza, DB, Zhang, JJ, Beck, LH, Meyer-Schwesinger, C, Luo, W. Mouse models of membranous nephropathy: the road less travelled by. Am J Clin Exp Immunol, 2(2), 135-45, 2013

Harrison, FE, Best, JL, Meredith, ME, Gamlin, CR, Borza, DB, May, JM, May, JM. Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung. PLoS One, 7(4), e35623, 2012

Ooi, JD, Chang, J, Hickey, MJ, Borza, DB, Fugger, L, Holdsworth, SR, Kitching, AR. The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. Proc Natl Acad Sci U S A, 109(39), E2615-24, 2012

Borza, DB, Fogo, AB. Interstitial mononuclear infiltrates in murine alpha3(IV)-NC1-induced nephropathy: harbingers of renal failure. Kidney Int, 82(9), 1033-4; author reply 1034, 2012

Zhang, JJ, Malekpour, M, Luo, W, Ge, L, Olaru, F, Wang, XP, Bah, M, Sado, Y, Heidet, L, Kleinau, S, Fogo, AB, Borza, DB. Murine Membranous Nephropathy: Immunization with alpha3(IV) Collagen Fragment Induces Subepithelial Immune Complexes and FcgammaR-Independent Nephrotic Syndrome. J Immunol, 188(7), 3268-77, 2012

Becknell, B, Zender, GA, Houston, R, Baker, PB, McBride, KL, Luo, W, Hains, DS, Borza, DB, and Schwaderer, AL. Novel X-linked glomerulopathy is associated with a COL4A5 missense mutation in a non-collagenous interruption. Kidney Int, 79(1), 120-7, 2011

Luo, W, Wang, XP, Kashtan, CE, and 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(6), 3520-8, 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(4), 343-354, 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, 2518-24, 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, 1471-9, 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(3), 731-34, 2009

Vanacore, RM, Ham, AJ, Cartailler, JP, Sundaramoorthy, M, Todd, P, Pedchenko, V, Sado, Y, Borza, DB, and Hudson, BG. A Role for collagen IV crosslinks in conferring immune privilege to the Goodpasture autoantigen: Structural basis for the crypticity of B cell epitopes. J Biol Chem, 283(33), 22737-48, 2008

Kang, JS, Colon, S, Hellmark, T, Sado, Y, Hudson, BG, and Borza, DB. Identification of noncollagenous sites encoding specific interactions and quaternary assembly of alpha3alpha4alpha5(IV) collagen: Implications for Alport gene therapy. J Biol Chem, 283(50), 35070-77, 2008

Ho, J, Gibson, IW, Zacharias, J, Fervenza, F, Colon, S, and Borza, DB. Antigenic Heterogeneity of IgA Anti-GBM Disease: New Renal Targets of IgA Autoantibodies. Am J Kidney Dis, 52(4), 761-5, 2008

Shimizu, H, Aufschnaiter, R, Li, L, Sarras, MP, Borza, DB, Abrahamson, DR, Sado, Y, Zhang, X. The extracellular matrix of hydra is a porous sheet and contains type IV collagen. Zoology (Jena), 111(5), 410-8, 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 {alpha}3{alpha}4{alpha}5 Collagen IV Network. J Am Soc Nephrol, 19(4), 677-84, 2008

Xu, H, Hu, F, Sado, Y, Ninomiya, Y, Borza, DB, Ungvari, Z, Lagamma, EF, Csiszar, A, Nedergaard, M, Ballabh, P. Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. J Neurosci Res, 86, 1482-1500, 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

Cosgrove, D, Kalluri, R, Miner, JH, Segal, Y, and Borza, DB. Choosing a mouse model to study the molecular pathobiology of Alport glomerulonephritis. Kidney Int, 71(7), 615-8, 2007

Fox, MA, Sanes, JR, Borza, DB, Eswarakumar, VP, F??ssler, 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(1), 179-93, 2007

Steenhard, BM, Freeburg, PB, Isom, K, Stroganova, L, Borza, DB, Hudson, BG, St John, PL, Zelenchuk, A, Abrahamson, DR. Kidney development and gene expression in the HIF2alpha knockout mouse. Dev Dyn, 236(4), 1115-1125, 2007

Kang, JS, Kashtan, CE, Turner, AN, Heidet, L, Hudson, BG, and Borza, DB. The Alloantigenic Sites of {alpha}3{alpha}4{alpha}5(IV) Collagen: Pathogenic X-Linked Alport Alloantibodies Target Two Accessible Conformational Epitopes in the {alpha}5NC1 Domain. J Biol Chem, 282(14), 10670-7, 2007

Borza, DB. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis. Nephron Exp Nephrol, 106(2), e37-43, 2007

Kang, JS, Wang, XP, Miner, JH, Morello, R, Sado, Y, Abrahamson, DR, and Borza, DB. Loss of {alpha}3/{alpha}4(IV) Collagen from the Glomerular Basement Membrane Induces a Strain-Dependent Isoform Switch to {alpha}5{alpha}6(IV) Collagen Associated with Longer Renal Survival in Col4a3-/- Alport Mice. J Am Soc Nephrol, 17(7), 1962-9, 2006

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, 281(30), 20932-9, 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, 460-70, 2006

Wang, XP, Fogo, AB, Colon, S, Giannico, G, Abul-Ezz, SR, Miner, JH, and 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(12), 3563-71, 2005

Borza, DB, Chedid, MF, Colon, S, Lager, DJ, Leung, N, Fervenza, FC. Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen. Am J Kidney Dis, 45(2), 397-406, 2005

Borza, DB. Life without histidine-rich glycoprotein: modulation of the hemostatic balance revisited. J Thromb Haemost, 3(5), 863-4, 2005

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(29), 27147-54, 2005

Borza, DB, Shipulina, NV, Morgan, WT. Effects of histidine-proline-rich glycoprotein on plasminogen activation in solution and on surfaces. Blood Coagul Fibrinolysis, 15(8), 663-72, 2004

Borza, DB, Neilson, EG, Hudson, BG. Pathogenesis of Goodpasture syndrome: a molecular perspective. Semin Nephrol, 23(6), 522-31, 2003

Borza, DB, Hudson BG . Molecular characterization of the target antigens of anti-glomerular basement membrane antibody disease. Springer Semin Immunopathol, 24, 345-61, 2003

Heidet, L, Borza, DB, Jouin, M, Sich, M, Mattei, MG, Sado, Y, Hudson, BG, Hastie, N, Antignac, C, Gubler, MC. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice. Am J Pathol, 163(4), 1633-44, 2003

Borza, DB, Bondar O, Todd P, Sundaramoorthy M, Sado Y, Ninomiya Y, Hudson BG . Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the alpha4 and alpha5 NC1 domains. J Biol Chem, 277, 40075-83, 2002

Borza, DB, Hudson BG . Of mice and men: murine models of anti-GBM antibody nephritis. Kidney Int, 61, 1905-6, 2002

Borza, DB, Bondar O, Ninomiya Y, Sado Y, Naito I, Todd P, Hudson BG . The NC1 domain of collagen IV encodes a novel network composed of the alpha 1, alpha 2, alpha 5, and alpha 6 chains in smooth muscle basement membranes. J Biol Chem, 276, 28532-40, 2001

David M, Borza, DB (co-first author), Leinonen A, Belmont JM, Hudson BG . Hydrophobic amino acid residues are critical for the immunodominant epitope of the Goodpasture autoantigen. A molecular basis for the cryptic nature of the epitope. J Biol Chem, 276, 6370-7, 2001

Borza, DB, Netzer KO, Leinonen A, Todd P, Cervera J, Saus J, Hudson BG . The goodpasture autoantigen. Identification of multiple cryptic epitopes on the NC1 domain of the alpha3(IV) collagen chain. J Biol Chem, 275, 6030-7, 2000

Boutaud A, Borza, DB (co-first author), Bondar O, Gunwar S, Netzer KO, Singh N, Ninomiya Y, Sado Y, Noelken ME, Hudson BG . Type IV collagen of the glomerular basement membrane. Evidence that the chain specificity of network assembly is encoded by the noncollagenous NC1 domains. J Biol Chem, 275, 30716-24, 2000

Netzer KO, Leinonen A, Boutaud A, Borza, DB, Todd P, Gunwar S, Langeveld JP, Hudson BG . The Goodpasture autoantigen. Mapping the major conformational epitope(s) of alpha3(IV) collagen to residues 17-31 and 127-141 of the NC1 domain. J Biol Chem, 274, 11267-74, 1999

Borza, DB, Morgan WT. Histidine-proline-rich glycoprotein as a plasma pH sensor. Modulation of its interaction with glycosaminoglycans by ph and metals. J Biol Chem, 273(10), 5493-9, 1998

Borza, DB, Morgan WT. Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein. J Biol Chem, 272(9), 5718-26, 1997

Borza, DB, Tatum FM, Morgan WT. Domain structure and conformation of histidine-proline-rich glycoprotein. Biochemistry, 35(6), 1925-34, 1996