
Roberto M Vanacore PhD
Department: Medicine
Biography
The focus of Dr Vanacore’s research is the study of basement membrane proteins, particularly collagen IV and its modifying enzymes, which are involved in life-threatening human diseases such as diabetic nephropathy, vascular disease, Goodpasture disease, and Alport syndrome. Collagen IV forms crosslinked supramolecular scaffolds that are essential for the mechanical stability of basement membranes and act as ligands for integrins influencing cell behaviors such as proliferation, differentiation, and migration. Dr. Vanacore has made important discoveries about the chemistry and pathology of basement membranes, including the discovery and assembly of the novel evolutionary conserved sulfilimine bond (S=N) that crosslinks the carboxyl-terminal NC1 domain of collagen IV, the first of its kind in a biomolecule. More recently, Dr Vanacore is investigating the role of the crosslinking enzyme lysyl oxidase on the stabilization of collagen IV scaffold. These investigations pursue a better understanding of these basement membrane proteins in normal tissue function and development as well as in pathological states, including renal fibrosis and tumorigenesis. For our investigations we use state-of-the-art mass spectrometry-based proteomics and bioinformatics tools in addition to a variety of biochemical, molecular and cell biology techniques.
Featured Publications
1. Extracellular chloride signals collagen IV network assembly during basement membrane formation.
Cummings CF, Pedchenko V, Brown KL, Colon S, Rafi M, Jones-Paris C, Pokydeshava E, Liu M, Pastor-Pareja JC, Stothers C, Ero-Tolliver IA, McCall AS, Vanacore R, Bhave G, Santoro S, Blackwell TS, Zent R, Pozzi A, Hudson BG (2016) J Cell Biol 213(4): 479-94
Citation ⋅ 27216258 (PubMed) PMC4878091 (PubMed Central)2. Aquaporin 11 variant associates with kidney disease in type 2 diabetic patients.
Choma DP, Vanacore R, Naylor H, Zimmerman IA, Pavlichenko A, Pavlichenko A, Foye L, Carbone DP, Harris RC, Dikov MM, Tchekneva EE (2016) Am J Physiol Renal Physiol 310(5): F416-25
Citation ⋅ 26719361 (PubMed) PMC4773830 (PubMed Central)3. Comprehensive Characterization of Glycosylation and Hydroxylation of Basement Membrane Collagen IV by High-Resolution Mass Spectrometry.
Basak T, Vega-Montoto L, Zimmerman LJ, Tabb DL, Hudson BG, Vanacore RM (2016) J Proteome Res 15(1): 245-58
Citation ⋅ 26593852 (PubMed) PMC4771517 (PubMed Central)Publications
1. Extracellular chloride signals collagen IV network assembly during basement membrane formation.
Cummings CF, Pedchenko V, Brown KL, Colon S, Rafi M, Jones-Paris C, Pokydeshava E, Liu M, Pastor-Pareja JC, Stothers C, Ero-Tolliver IA, McCall AS, Vanacore R, Bhave G, Santoro S, Blackwell TS, Zent R, Pozzi A, Hudson BG (2016) J Cell Biol 213(4): 479-94
Citation ⋅ 27216258 (PubMed) PMC4878091 (PubMed Central)2. Aquaporin 11 variant associates with kidney disease in type 2 diabetic patients.
Choma DP, Vanacore R, Naylor H, Zimmerman IA, Pavlichenko A, Pavlichenko A, Foye L, Carbone DP, Harris RC, Dikov MM, Tchekneva EE (2016) Am J Physiol Renal Physiol 310(5): F416-25
Citation ⋅ 26719361 (PubMed) PMC4773830 (PubMed Central)3. Comprehensive Characterization of Glycosylation and Hydroxylation of Basement Membrane Collagen IV by High-Resolution Mass Spectrometry.
Basak T, Vega-Montoto L, Zimmerman LJ, Tabb DL, Hudson BG, Vanacore RM (2016) J Proteome Res 15(1): 245-58
Citation ⋅ 26593852 (PubMed) PMC4771517 (PubMed Central)4. Supramolecular organization of the α121-α565 collagen IV network.
Robertson WE, Rose KL, Hudson BG, Vanacore RM (2014) J Biol Chem 289(37): 25601-10
Citation ⋅ 25006246 (PubMed) PMC4162165 (PubMed Central)5. Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling.
Chen X, Wang H, Liao HJ, Hu W, Gewin L, Mernaugh G, Zhang S, Zhang ZY, Vega-Montoto L, Vanacore RM, Fässler R, Zent R, Pozzi A (2014) J Clin Invest 124(8): 3295-310
Citation ⋅ 24983314 (PubMed) PMC4109532 (PubMed Central)6. Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.
McCall AS, Cummings CF, Bhave G, Vanacore R, Page-McCaw A, Hudson BG (2014) Cell 157(6): 1380-92
Citation ⋅ 24906154 (PubMed) PMC4144415 (PubMed Central)7. 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
Citation ⋅ 24344311 (PubMed) PMC3890831 (PubMed Central)8. Upregulated expression of integrin α1 in mesangial cells and integrin α3 and vimentin in podocytes of Col4a3-null (Alport) mice.
Steenhard BM, Vanacore R, Friedman D, Zelenchuk A, Stroganova L, Isom K, St John PL, Hudson BG, Abrahamson DR (2012) PLoS One 7(12): e50745
Citation ⋅ 23236390 (PubMed) PMC3517557 (PubMed Central)9. Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis.
Bhave G, Cummings CF, Vanacore RM, Kumagai-Cresse C, Ero-Tolliver IA, Rafi M, Kang JS, Pedchenko V, Fessler LI, Fessler JH, Hudson BG (2012) Nat Chem Biol 8(9): 784-90
Citation ⋅ 22842973 (PubMed) PMC4128002 (PubMed Central)10. Sulphilimine cross-links in Goodpasture's disease.
Vanacore R, Pedchenko V, Bhave G, Hudson BG (2011) Clin Exp Immunol 164 Suppl 1(): 4-6
Citation ⋅ 21447121 (PubMed) PMC3095855 (PubMed Central)11. Goodpasture's disease: molecular architecture of the autoantigen provides clues to etiology and pathogenesis.
Pedchenko V, Vanacore R, Hudson B (2011) Curr Opin Nephrol Hypertens 20(3): 290-6
Citation ⋅ 21378566 (PubMed) PMC3159420 (PubMed Central)12. 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
Citation ⋅ 20660402 (PubMed) PMC4144421 (PubMed Central)13. A sulfilimine bond identified in collagen IV.
Vanacore R, Ham AJ, Voehler M, Sanders CR, Conrads TP, Veenstra TD, Sharpless KB, Dawson PE, Hudson BG (2009) Science 325(5945): 1230-4
Citation ⋅ 19729652 (PubMed) PMC2876822 (PubMed Central)14. 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
Citation ⋅ 18499662 (PubMed) PMC2504875 (PubMed Central)15. Identification of S-hydroxylysyl-methionine as the covalent cross-link of the noncollagenous (NC1) hexamer of the alpha1alpha1alpha2 collagen IV network: a role for the post-translational modification of lysine 211 to hydroxylysine 211 in hexamer assembly.
Vanacore RM, Friedman DB, Ham AJ, Sundaramoorthy M, Hudson BG (2005) J Biol Chem 280(32): 29300-10
Citation ⋅ 15951440 (PubMed)16. The alpha1.alpha2 network of collagen IV. Reinforced stabilization of the noncollagenous domain-1 by noncovalent forces and the absence of Met-Lys cross-links.
Vanacore RM, Shanmugasundararaj S, Friedman DB, Bondar O, Hudson BG, Sundaramoorthy M (2004) J Biol Chem 279(43): 44723-30
Citation ⋅ 15299013 (PubMed)17. Plasma exchange for polyradiculoneuropathy following kidney transplantation: a case report.
Mazzoni A, Pardi C, Bortoli M, Mariotti ML, Uncini Manganelli C, Vanacore R, Stampacchia G, Boggi U, Ghilli M, Vistoli F, Mosca F, Scatena F (2004) Transplant Proc 36(3): 716-7
Citation ⋅ 15110642 (PubMed)18. Role for copper in transient oxidation and nuclear translocation of MTF-1, but not of NF-kappa B, by the heme-hemopexin transport system.
Vanacore RM, Eskew JD, Morales PJ, Sung L, Smith A (2000) Antioxid Redox Signal 2(4): 739-52
Citation ⋅ 11213479 (PubMed)19. Cellular protection mechanisms against extracellular heme. heme-hemopexin, but not free heme, activates the N-terminal c-jun kinase.
Eskew JD, Vanacore RM, Sung L, Morales PJ, Smith A (1999) J Biol Chem 274(2): 638-48
Citation ⋅ 9872997 (PubMed)