Dorin Bogdan Borza, Ph.D.

Profile

Research Interests: My research focuses on understanding the molecular patho-mechanisms of antibody-mediated glomerular disease. My lab has studied the structure of type IV collagen and its role in inherited and immune diseases affecting the glomerular basement membrane (GBM). We are using the paradigm of Goodpasture disease to address the mechanisms eliciting abnormal immune responses against α345(IV) collagen and how the resulting anti-GBM antibodies mediate glomerulonephritis. This work has elucidated the organization of Goodpasture autoantigen and other collagen IV networks and the mechanisms of their specific assembly, providing a framework for understanding how tolerance to collagen IV is established in health and breached in anti-GBM antibody disease. We have discovered how the assembly of α345(IV) collagen into quaternary structures hides cryptic B cell auto-epitopes while also creating new quaternary epitopes, thereby shaping immune tolerance and autoimmune responses toward collagen IV. Our current efforts are directed at solving the conundrum of how predominantly IgG4 immune complexes activate complement in membranous nephropathy. 

Publications

The following timeline graph is generated from all co-authored publications.

1. Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation. Borza DB (2017) Matrix Biol : 299-310
   › Primary publication · 27609404 (PubMed) · PMC5026315 (PubMed Central)
2. Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy. Borza DB (2016) Front Immunol : 157
   › Primary publication · 27199983 (PubMed) · PMC4842769 (PubMed Central)
3. Distinct roles for the complement regulators factor H and Crry in protection of the kidney from injury. Laskowski J, Renner B, Le Quintrec M, Panzer S, Hannan JP, Ljubanovic D, Ruseva MM, Borza DB, Antonioli AH, Pickering MC, Holers VM, Thurman JM (2016) Kidney Int 90(1): 109-22
   › Primary publication · 27165610 (PubMed) · PMC4912413 (PubMed Central)
4. A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy. Sueki H, Sato Y, Ohtoshi S, Nakada T, Yoshimura A, Tateishi C, Borza DB, Fader W, Ghohestani RF, Hirako Y, Koga H, Ishii N, Tsuchisaka A, Qian H, Li X, Hashimoto T (2015) Acta Derm Venereol 95(7): 826-9
   › Primary publication · 25633161 (PubMed)
5. Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways. Gomez IG, MacKenna DA, Johnson BG, Kaimal V, Roach AM, Ren S, Nakagawa N, Xin C, Newitt R, Pandya S, Xia TH, Liu X, Borza DB, Grafals M, Shankland SJ, Himmelfarb J, Portilla D, Liu S, Chau BN, Duffield JS (2015) J Clin Invest 125(1): 141-56
   › Primary publication · 25415439 (PubMed) · PMC4382246 (PubMed Central)
6. IgG4-restricted anti-glomerular basement membrane autoantibodies targeting quaternary epitopes of native α345(IV) collagen. Borza DB (2014) Am J Kidney Dis 64(1): 156-7
   › Primary publication · 24954454 (PubMed)
7. Neonatal Fc receptor promotes immune complex-mediated glomerular disease. Olaru F, Luo W, Suleiman H, St John PL, Ge L, Mezo AR, Shaw AS, Abrahamson DR, Miner JH, Borza DB (2014) J Am Soc Nephrol 25(5): 918-25
   › Primary publication · 24357670 (PubMed) · PMC4005300 (PubMed Central)
8. A unique covalent bond in basement membrane is a primordial innovation for tissue evolution. Fidler AL, Vanacore RM, Chetyrkin SV, Pedchenko VK, Bhave G, Yin VP, Stothers CL, Rose KL, McDonald WH, Clark TA, Borza DB, Steele RE, Ivy MT, Aspirnauts, Hudson JK, Hudson BG (2014) Proc Natl Acad Sci U S A 111(1): 331-6
   › Primary publication · 24344311 (PubMed) · PMC3890831 (PubMed Central)
9. Repeatability and sensitivity of high resolution blood volume mapping in mouse kidney disease. Wang F, Jiang RT, Tantawy MN, Borza DB, Takahashi K, Gore JC, Harris RC, Takahashi T, Quarles CC (2014) J Magn Reson Imaging 39(4): 866-71
   › Primary publication · 24006202 (PubMed) · PMC3858530 (PubMed Central)
10. Mouse models of membranous nephropathy: the road less travelled by. Borza DB, Zhang JJ, Beck LH, Meyer-Schwesinger C, Luo W (2013) Am J Clin Exp Immunol 2(2): 135-45
    › Primary publication · 23885331 (PubMed) · PMC3714174 (PubMed Central)
11. Quaternary epitopes of α345(IV) collagen initiate Alport post-transplant anti-GBM nephritis. Olaru F, Luo W, Wang XP, Ge L, Hertz JM, Kashtan CE, Sado Y, Segal Y, Hudson BG, Borza DB (2013) J Am Soc Nephrol 24(6): 889-95
    › Primary publication · 23620401 (PubMed) · PMC3665397 (PubMed Central)
12. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-glomerular basement membrane autoantibodies specific for α345NC1 hexamers. Olaru F, Wang XP, Luo W, Ge L, Miner JH, Kleinau S, Geiger XJ, Wasiluk A, Heidet L, Kitching AR, Borza DB (2013) J Immunol 190(4): 1424-32
    › Primary publication · 23303673 (PubMed) · PMC3563930 (PubMed Central)
13. Interstitial mononuclear infiltrates in murine α3(IV)-NC1-induced nephropathy: harbingers of renal failure? Borza DB, Fogo AB (2012) Kidney Int 82(9): 1033-4; author reply 1034
    › Primary publication · 23064190 (PubMed) · PMC3698848 (PubMed Central)
14. The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. Ooi JD, Chang J, Hickey MJ, Borza DB, Fugger L, Holdsworth SR, Kitching AR (2012) Proc Natl Acad Sci U S A 109(39): E2615-24
    › Primary publication · 22955884 (PubMed) · PMC3465432 (PubMed Central)
15. Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung. Harrison FE, Best JL, Meredith ME, Gamlin CR, Borza DB, May JM, May JM (2012) PLoS One 7(4): e35623
    › Primary publication · 22558179 (PubMed) · PMC3340390 (PubMed Central)
16. Murine membranous nephropathy: immunization with α3(IV) collagen fragment induces subepithelial immune complexes and FcγR-independent nephrotic syndrome. Zhang JJ, Malekpour M, Luo W, Ge L, Olaru F, Wang XP, Bah M, Sado Y, Heidet L, Kleinau S, Fogo AB, Borza DB (2012) J Immunol 188(7): 3268-77
    › Primary publication · 22371398 (PubMed) · PMC3311769 (PubMed Central)
17. Novel X-linked glomerulopathy is associated with a COL4A5 missense mutation in a non-collagenous interruption. Becknell B, Zender GA, Houston R, Baker PB, McBride KL, Luo W, Hains DS, Borza DB, Schwaderer AL (2011) Kidney Int 79(1): 120-7
    › Primary publication · 20881942 (PubMed) · PMC3248803 (PubMed Central)
18. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo. Luo W, Wang XP, Kashtan CE, Borza DB (2010) J Immunol 185(6): 3520-8
    › Primary publication · 20709951 (PubMed) · PMC2951005 (PubMed Central)
19. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, Wilson CB, Hudson BG (2010) N Engl J Med 363(4): 343-54
    › Primary publication · 20660402 (PubMed) · PMC4144421 (PubMed Central)
20. Th1 and Th17 cells induce proliferative glomerulonephritis. Summers SA, Steinmetz OM, Li M, Kausman JY, Semple T, Edgtton KL, Borza DB, Braley H, Holdsworth SR, Kitching AR (2009) J Am Soc Nephrol 20(12): 2518-24
    › Primary publication · 19820122 (PubMed) · PMC2794236 (PubMed Central)
21. Cellular origins of type IV collagen networks in developing glomeruli. Abrahamson DR, Hudson BG, Stroganova L, Borza DB, St John PL (2009) J Am Soc Nephrol 20(7): 1471-9
    › Primary publication · 19423686 (PubMed) · PMC2709682 (PubMed Central)
22. Stem cell therapy for Alport syndrome: the hope beyond the hype. 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 (2009) Nephrol Dial Transplant 24(3): 731-4
    › Primary publication · 19110486 (PubMed) · PMC3888105 (PubMed Central)
23. Identification of noncollagenous sites encoding specific interactions and quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen: implications for Alport gene therapy. Kang JS, Colon S, Hellmark T, Sado Y, Hudson BG, Borza DB (2008) J Biol Chem 283(50): 35070-7
    › Primary publication · 18930919 (PubMed) · PMC2596392 (PubMed Central)
24. Antigenic heterogeneity of IgA anti-GBM disease: new renal targets of IgA autoantibodies. Ho J, Gibson IW, Zacharias J, Fervenza F, Colon S, Borza DB (2008) Am J Kidney Dis 52(4): 761-5
    › Primary publication · 18752876 (PubMed) · PMC2577053 (PubMed Central)
25. The extracellular matrix of hydra is a porous sheet and contains type IV collagen. Shimizu H, Aufschnaiter R, Li L, Sarras MP, Borza DB, Abrahamson DR, Sado Y, Zhang X (2008) Zoology (Jena) 111(5): 410-418
    › Primary publication · 18602803 (PubMed) · PMC2560992 (PubMed Central)
26. A role for collagen IV cross-links in conferring immune privilege to the Goodpasture autoantigen: structural basis for the crypticity of B cell epitopes. Vanacore RM, Ham AJ, Cartailler JP, Sundaramoorthy M, Todd P, Pedchenko V, Sado Y, Borza DB, Hudson BG (2008) J Biol Chem 283(33): 22737-48
    › Primary publication · 18499662 (PubMed) · PMC2504875 (PubMed Central)
27. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. 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 (2008) Dev Biol 316(2): 288-301
    › Primary publication · 18328474 (PubMed) · PMC2396524 (PubMed Central)
28. Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 collagen IV network. Borza CM, Borza DB, Pedchenko V, Saleem MA, Mathieson PW, Sado Y, Hudson HM, Pozzi A, Saus J, Abrahamson DR, Zent R, Hudson BG (2008) J Am Soc Nephrol 19(4): 677-84
    › Primary publication · 18235087 (PubMed) · PMC2390958 (PubMed Central)
29. Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. Xu H, Hu F, Sado Y, Ninomiya Y, Borza DB, Ungvari Z, Lagamma EF, Csiszar A, Nedergaard M, Ballabh P (2008) J Neurosci Res 86(7): 1482-500
    › Primary publication · 18214989 (PubMed)
30. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis. Borza DB (2007) Nephron Exp Nephrol 106(2): e37-43
    › Primary publication · 17570938 (PubMed)
31. Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals. 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 (2007) Cell 129(1): 179-93
    › Primary publication · 17418794 (PubMed)
32. Kidney development and gene expression in the HIF2alpha knockout mouse. Steenhard BM, Freeburg PB, Isom K, Stroganova L, Borza DB, Hudson BG, St John PL, Zelenchuk A, Abrahamson DR (2007) Dev Dyn 236(4): 1115-25
    › Primary publication · 17342756 (PubMed)
33. The alloantigenic sites of alpha3alpha4alpha5(IV) collagen: pathogenic X-linked alport alloantibodies target two accessible conformational epitopes in the alpha5NC1 domain. Kang JS, Kashtan CE, Turner AN, Heidet L, Hudson BG, Borza DB (2007) J Biol Chem 282(14): 10670-7
    › Primary publication · 17293596 (PubMed)
34. Choosing a mouse model to study the molecular pathobiology of Alport glomerulonephritis. Cosgrove D, Kalluri R, Miner JH, Segal Y, Borza DB (2007) Kidney Int 71(7): 615-8
    › Primary publication · 17290292 (PubMed)
35. Glomerular injury is exacerbated in diabetic integrin alpha1-null mice. Zent R, Yan X, Su Y, Hudson BG, Borza DB, Moeckel GW, Qi Z, Sado Y, Breyer MD, Voziyan P, Pozzi A (2006) Kidney Int 70(3): 460-70
    › Primary publication · 16775606 (PubMed)
36. 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. Kang JS, Wang XP, Miner JH, Morello R, Sado Y, Abrahamson DR, Borza DB (2006) J Am Soc Nephrol 17(7): 1962-9
    › Primary publication · 16769745 (PubMed)
37. Integrin alpha3beta1, a novel receptor for alpha3(IV) noncollagenous domain and a trans-dominant Inhibitor for integrin alphavbeta3. Borza CM, Pozzi A, Borza DB, Pedchenko V, Hellmark T, Hudson BG, Zent R (2006) J Biol Chem 281(30): 20932-20939
    › Primary publication · 16731529 (PubMed)
38. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. Wang XP, Fogo AB, Colon S, Giannico G, Abul-Ezz SR, Miner JH, Borza DB (2005) J Am Soc Nephrol 16(12): 3563-71
    › Primary publication · 16236801 (PubMed)
39. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis. Borza DB, Bondar O, Colon S, Todd P, Sado Y, Neilson EG, Hudson BG (2005) J Biol Chem 280(29): 27147-54
    › Primary publication · 15917228 (PubMed)
40. Life without histidine-rich glycoprotein: modulation of the hemostatic balance revisited. Borza DB (2005) J Thromb Haemost 3(5): 863-4
    › Primary publication · 15869578 (PubMed)
41. Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen. Borza DB, Chedid MF, Colon S, Lager DJ, Leung N, Fervenza FC (2005) Am J Kidney Dis 45(2): 397-406
    › Primary publication · 15685519 (PubMed)
42. Effects of histidine-proline-rich glycoprotein on plasminogen activation in solution and on surfaces. Borza DB, Shipulina NV, Morgan WT (2004) Blood Coagul Fibrinolysis 15(8): 663-72
    › Primary publication · 15613921 (PubMed)
43. Pathogenesis of Goodpasture syndrome: a molecular perspective. Borza DB, Neilson EG, Hudson BG (2003) Semin Nephrol 23(6): 522-31
    › Primary publication · 14631560 (PubMed)
44. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice. Heidet L, Borza DB, Jouin M, Sich M, Mattei MG, Sado Y, Hudson BG, Hastie N, Antignac C, Gubler MC (2003) Am J Pathol 163(4): 1633-44
    › Primary publication · 14507670 (PubMed) · PMC1868284 (PubMed Central)
45. Molecular characterization of the target antigens of anti-glomerular basement membrane antibody disease. Borza DB, Hudson BG (2003) Springer Semin Immunopathol 24(4): 345-61
    › Primary publication · 12778332 (PubMed)
46. 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. Borza DB, Bondar O, Todd P, Sundaramoorthy M, Sado Y, Ninomiya Y, Hudson BG (2002) J Biol Chem 277(42): 40075-83
    › Primary publication · 12193605 (PubMed)
47. Of mice and men: murine models of anti-GBM antibody nephritis. Borza DB, Hudson BG (2002) Kidney Int 61(5): 1905-6
    › Primary publication · 11967044 (PubMed)
48. 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. Borza DB, Bondar O, Ninomiya Y, Sado Y, Naito I, Todd P, Hudson BG (2001) J Biol Chem 276(30): 28532-40
    › Primary publication · 11375996 (PubMed)
49. Hydrophobic amino acid residues are critical for the immunodominant epitope of the Goodpasture autoantigen. A molecular basis for the cryptic nature of the epitope. David M, Borza DB, Leinonen A, Belmont JM, Hudson BG (2001) J Biol Chem 276(9): 6370-7
    › Primary publication · 11098057 (PubMed)
50. Type IV collagen of the glomerular basement membrane. Evidence that the chain specificity of network assembly is encoded by the noncollagenous NC1 domains. Boutaud A, Borza DB, Bondar O, Gunwar S, Netzer KO, Singh N, Ninomiya Y, Sado Y, Noelken ME, Hudson BG (2000) J Biol Chem 275(39): 30716-24
    › Primary publication · 10896941 (PubMed)
51. The goodpasture autoantigen. Identification of multiple cryptic epitopes on the NC1 domain of the alpha3(IV) collagen chain. Borza DB, Netzer KO, Leinonen A, Todd P, Cervera J, Saus J, Hudson BG (2000) J Biol Chem 275(8): 6030-7
    › Primary publication · 10681598 (PubMed)
52. The goodpasture autoantigen. Mapping the major conformational epitope(s) of alpha3(IV) collagen to residues 17-31 and 127-141 of the NC1 domain. Netzer KO, Leinonen A, Boutaud A, Borza DB, Todd P, Gunwar S, Langeveld JP, Hudson BG (1999) J Biol Chem 274(16): 11267-74
    › Primary publication · 10196215 (PubMed)
53. Histidine-proline-rich glycoprotein as a plasma pH sensor. Modulation of its interaction with glycosaminoglycans by ph and metals. Borza DB, Morgan WT (1998) J Biol Chem 273(10): 5493-9
    › Primary publication · 9488672 (PubMed)
54. Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein. Borza DB, Morgan WT (1997) J Biol Chem 272(9): 5718-26
    › Primary publication · 9102401 (PubMed)
55. Domain structure and conformation of histidine-proline-rich glycoprotein. Borza DB, Tatum FM, Morgan WT (1996) Biochemistry 35(6): 1925-34
    › Primary publication · 8639676 (PubMed)

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