Roberto M. Vanacore, Ph.D.

Assistant Professor

roberto.vanacore@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Medicine
Education
Ph.D., Biochemistry, University of Kansas, Kansas City, KansasM.S., Biochemistry, Universidad Austral de Chile, Valdivia, Chile
Office Address
S-3223 MCN
1161 21st Ave South
Nashville, TN 37232-2372
Research Description
The focus of Dr Vanacore’s research is the study of extracellular matrix (ECM) 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 collagen crosslinking enzyme lysyl oxidase like-2 (LOXL2) in renal fibrosis. These investigations pursue a better understanding of role of these ECM proteins in normal tissue function and development of chronic kidney disease. For our investigations we use transgenic mouse models of kidney disease in combination with state-of-the-art mass spectrometry-based proteomics and a variety of biochemical, molecular and cell biology techniques.
Research Keywords
Biochemistry, Protein Structure, Post-translational Modifications, Mass Spectrometry, Proteomics, Basement Membrane, Extracellular Matrix, Matrix Biology, Diabetic Nephropathy, Glomeruosclerosis and Kidney Disease
Publications
Quantitative Proteomic Profiling of Extracellular Matrix and collagen post-translational modifications induced by transforming growth factor-ß1 on the lung fibroblast. Matrix Biology Plus. 2019 May.

Vanacore R, Eskew JD, Sung L, Davis T, Smith A. Safe coordinated trafficking of heme and iron with copper maintain cell homeostasis: modules from the hemopexin system. Biometals [print-electronic]. 2019 Apr 4/22/2019; PMID: 31011852, PII: 10.1007/s10534-019-00194-4, DOI: 10.1007/s10534-019-00194-4, ISSN: 1572-8773.

Brown KL, Cummings CF, Vanacore RM, Hudson BG. Building collagen IV smart scaffolds on the outside of cells. Protein Sci. 2017 Nov; 26(11): 2151-61. PMID: 28845540, PMCID: PMC5654846, DOI: 10.1002/pro.3283, ISSN: 1469-896X.

López-Jiménez AJ, Basak T, Vanacore RM. Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV. J. Biol. Chem [print-electronic]. 2017 Oct 10/13/2017; 292(41): 16970-82. PMID: 28864775, PMCID: PMC5641870, PII: M117.798603, DOI: 10.1074/jbc.M117.798603, ISSN: 1083-351X.

Añazco C, López-Jiménez AJ, Rafi M, Vega-Montoto L, Zhang MZ, Hudson BG, Vanacore RM. Lysyl Oxidase-like-2 Cross-links Collagen IV of Glomerular Basement Membrane. J. Biol. Chem [print-electronic]. 2016 Dec 12/9/2016; 291(50): 25999-6012. PMID: 27770022, PMCID: PMC5207071, PII: M116.738856, DOI: 10.1074/jbc.M116.738856, ISSN: 1083-351X.

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. Extracellular chloride signals collagen IV network assembly during basement membrane formation. J. Cell Biol. 2016 May 5/23/2016; 213(4): 479-94. PMID: 27216258, PMCID: PMC4878091, PII: jcb.201510065, DOI: 10.1083/jcb.201510065, ISSN: 1540-8140.

Choma DP, Vanacore R, Naylor H, Zimmerman IA, Pavlichenko A, Pavlichenko A, Foye L, Carbone DP, Harris RC, Dikov MM, Tchekneva EE. Aquaporin 11 variant associates with kidney disease in type 2 diabetic patients. Am. J. Physiol. Renal Physiol [print-electronic]. 2016 Mar 3/1/2016; 310(5): F416-25. PMID: 26719361, PMCID: PMC4773830, PII: ajprenal.00295.2015, DOI: 10.1152/ajprenal.00295.2015, ISSN: 1522-1466.

Basak T, Vega-Montoto L, Zimmerman LJ, Tabb DL, Hudson BG, Vanacore RM. Comprehensive Characterization of Glycosylation and Hydroxylation of Basement Membrane Collagen IV by High-Resolution Mass Spectrometry. J. Proteome Res [print-electronic]. 2016 Jan 1/4/2016; 15(1): 245-58. PMID: 26593852, PMCID: PMC4771517, DOI: 10.1021/acs.jproteome.5b00767, ISSN: 1535-3907.

Robertson WE, Rose KL, Hudson BG, Vanacore RM. Supramolecular organization of the a121-a565 collagen IV network. J. Biol. Chem [print-electronic]. 2014 Sep 9/12/2014; 289(37): 25601-10. PMID: 25006246, PMCID: PMC4162165, PII: M114.571844, DOI: 10.1074/jbc.M114.571844, ISSN: 1083-351X.

McCall AS, Cummings CF, Bhave G, Vanacore R, Page-McCaw A, Hudson BG. Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture. Cell. 2014 Jun 6/5/2014; 157(6): 1380-92. PMID: 24906154, PMCID: PMC4144415, PII: S0092-8674(14)00598-4, DOI: 10.1016/j.cell.2014.05.009, ISSN: 1097-4172.

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, , Hudson JK, Hudson BG. A unique covalent bond in basement membrane is a primordial innovation for tissue evolution. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Jan 1/7/2014; 111(1): 331-6. PMID: 24344311, PMCID: PMC3890831, PII: 1318499111, DOI: 10.1073/pnas.1318499111, ISSN: 1091-6490.

McCall AS*, Cummings CF*, Bhave G*, Vanacore RM, Page-McCaw A, and Hudson BG. ¿¿¿Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture¿¿¿. 2014.

Chen X, Wang H, Liao H, Hu W, Gewin L, Mernaugh G, Zhang S, Zhang S-Y, Vega-Montoto L, Vanacore RM, F¿¿ssler R, Zent R, Pozzi A.. ¿¿¿Integrin ¿¿1¿¿1-mediated tyrosine dephosphorylation of the type II TGF-¿¿ receptor controls Smad-dependent pro-fibrotic signaling¿¿¿. 2014.

Robertson WE, Rose KL, Hudson BG, Vanacore RM. ¿¿¿Supramolecular Organization of the ¿¿121-¿¿565 Collagen IV Network¿¿¿. 2014.

Bhave G, Cummings CF, Vanacore RM, Kumagai-Cresse C, Ero-Tolliver IA, Rafi M, Kang JS, Pedchenko V, Fessler LI, Fessler JH, Hudson BG. Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis. Nat. Chem. Biol [print-electronic]. 2012 Sep; 8(9): 784-90. PMID: 22842973, PMCID: PMC4128002, PII: nchembio.1038, DOI: 10.1038/nchembio.1038, ISSN: 1552-4469.

Steenhard BM, Vanacore R, Friedman D, Zelenchuk A, Stroganova L, Isom K, St John PL, Hudson BG, Abrahamson DR. Upregulated expression of integrin a1 in mesangial cells and integrin a3 and vimentin in podocytes of Col4a3-null (Alport) mice. PLoS ONE [print-electronic]. 2012; 7(12): e50745. PMID: 23236390, PMCID: PMC3517557, PII: PONE-D-12-29453, DOI: 10.1371/journal.pone.0050745, ISSN: 1932-6203.

Vanacore R, Pedchenko V, Bhave G, Hudson BG. Sulphilimine cross-links in Goodpasture's disease. Clin. Exp. Immunol. 2011 May; 164 Suppl 1: 4-6. PMID: 21447121, PMCID: PMC3095855, DOI: 10.1111/j.1365-2249.2011.04356.x, ISSN: 1365-2249.

Pedchenko V, Vanacore R, Hudson B. Goodpasture's disease: molecular architecture of the autoantigen provides clues to etiology and pathogenesis. Curr. Opin. Nephrol. Hypertens. 2011 May; 20(3): 290-6. PMID: 21378566, PMCID: PMC3159420, DOI: 10.1097/MNH.0b013e328344ff20, ISSN: 1473-6543.

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. 2010 Jul 7/22/2010; 363(4): 343-54. PMID: 20660402, PMCID: PMC4144421, PII: 363/4/343, DOI: 10.1056/NEJMoa0910500, ISSN: 1533-4406.

Vanacore R, Ham AJ, Voehler M, Sanders CR, Conrads TP, Veenstra TD, Sharpless KB, Dawson PE, Hudson BG. A sulfilimine bond identified in collagen IV. Science. 2009 Sep 9/4/2009; 325(5945): 1230-4. PMID: 19729652, PMCID: PMC2876822, PII: 325/5945/1230, DOI: 10.1126/science.1176811, ISSN: 1095-9203.

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 [print-electronic]. 2008 Aug 8/15/2008; 283(33): 22737-48. PMID: 18499662, PMCID: PMC2504875, PII: M803451200, DOI: 10.1074/jbc.M803451200, ISSN: 0021-9258.

Vanacore RM, Friedman DB, Ham AJ, Sundaramoorthy M, Hudson BG. 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. J. Biol. Chem [print-electronic]. 2005 Aug 8/12/2005; 280(32): 29300-10. PMID: 15951440, PII: M502752200, DOI: 10.1074/jbc.M502752200, ISSN: 0021-9258.

Vanacore RM, Shanmugasundararaj S, Friedman DB, Bondar O, Hudson BG, Sundaramoorthy M. 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. J. Biol. Chem [print-electronic]. 2004 Oct 10/22/2004; 279(43): 44723-30. PMID: 15299013, PII: M406344200, DOI: 10.1074/jbc.M406344200, ISSN: 0021-9258.

Vanacore RM, Eskew JD, Morales PJ, Sung L, Smith A. Role for copper in transient oxidation and nuclear translocation of MTF-1, but not of NF-kappa B, by the heme-hemopexin transport system. Antioxid. Redox Signal. 2000; 2(4): 739-52. PMID: 11213479, ISSN: 1523-0864.

Eskew JD, Vanacore RM, Sung L, Morales PJ, Smith A. Cellular protection mechanisms against extracellular heme. heme-hemopexin, but not free heme, activates the N-terminal c-jun kinase. J. Biol. Chem. 1999 Jan 1/8/1999; 274(2): 638-48. PMID: 9872997, ISSN: 0021-9258.

Available Postdoctoral Position Details
Posted: 5/9/2019

Postdoctoral Research fellowship

Center for Matrix Biology - Division of Nephrology

Vanderbilt University Medical Center, Nashville TN


Job Description

A NIH-funded postdoctoral fellowship is available immediately in the laboratory of Dr. Roberto Vanacore to investigate molecular mechanisms of renal fibrosis in chronic kidney disease. We use animal models in combination of cutting-edge technologies in proteomics/mass spectrometry, biochemistry and molecular/cell biology to investigate the structure-function relationship of collagen and its modifying enzymes on the biosynthesis, assembly and function of the renal extracellular matrix. Consistent with our laboratory efforts to identify novel potential therapies for renal disease, the candidate will have the opportunity to pursue translational research in collaboration with pharmaceutical companies by testing novel compounds designed to inhibit the development and progression of kidney fibrosis. The Vanacore Lab is housed in the Division of Nephrology and is part of the Vanderbilt Center for Kidney Disease and Center for Matrix Biology.


Candidate Skills

We are seeking a highly motivated recent PhD graduate with experience in protein biochemistry and molecular/cell biology. The ideal candidate will be proficient in the design, cloning, purification and functional characterization of recombinant enzymes. A desire to deepen proficiency in protein biochemistry by learning mass spectrometry/proteomics will be a good fit as our Lab can provide excellent training opportunities in a great environment. Mouse work experience is preferred, although not a requirement as the laboratory can provide training to models of renal disease. Ability to think and work independently as well as a creative and critical mindset are key features for a successful candidate. Excellent oral and written communication skills and the ability to work as a team member are essential. Participation in grant and manuscript writing is expected. Preference will be given to individuals pursuing an academic career with a strong desire to drive projects to completion and publish as a lead author.

Requirements and Benefits

This is a full-time position that requires a PhD degree (Biochemistry, Molecular/Cell Biology, or related discipline). Salary is based on NIH pay scale starting from $50,004. Vanderbilt also offers an excellent benefits package including a retirement plan, health and dental insurance, etc. More information about postdoctoral positions, available resources and relocation to Nashville, TN can be found at the BRET office (https://medschool.vanderbilt.edu/postdoc/)

Please submit a cover letter describing previous professional experiences, a summary of your current work, future plans and expectations. When listing publications please include a brief summary of your role and contributions to the study. The letter, CV and contact information for at least 3 references should be sent to roberto.vanacore@vanderbilt.edu.