Kyle L. Brown, Ph.D.

Research Assistant Professor
Faculty Appointments
Research Assistant Professor of Medicine
Ph.D., Biophysical Chemistry, Vanderbilt University, Nashville, TennesseeB.S., Chemical Physics, Union University, Jackson, Tennessee
Research Description
Dr. Brown received his PhD in chemistry at Vanderbilt. Structure, dynamics, and intermolecular interactions that are the basis for biological macromolecular function. Dr. Brown uses NMR spectroscopy, X-ray crystallography, and other experimental biophysical techniques in conjunction with molecular dynamics simulations to decipher the molecular mechanisms of nephropathy at the atomic level. This work is focused on understanding the molecular architecture and assembly mechanisms of the extracellular matrix (ECM), especially the scaffolding properties of collagen IV networks. By analyzing the impact of covalent modifications to ECM components identified in diabetic patients and animal models, Dr. Brown correlates the relationship between modified proteins and their altered function in kidney disease. The overall goal of this work is to decode the basic mechanisms of nephropathy for the purpose of designing better therapeutic strategies.
Cui Z, Zhao MH, Jia XY, Wang M, Hu SY, Wang SX, Yu F, Brown KL, Hudson BG, Pedchenko V. Antibodies to a5 chain of collagen IV are pathogenic in Goodpasture's disease. J. Autoimmun [print-electronic]. 2016 Jun; 70: 1-11. PMID: 27117167, PII: S0896-8411(16)30033-6, DOI: 10.1016/j.jaut.2016.04.001, ISSN: 1095-9157.

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.

Brown KL, Darris C, Rose KL, Sanchez OA, Madu H, Avance J, Brooks N, Zhang MZ, Fogo A, Harris R, Hudson BG, Voziyan P. Hypohalous acids contribute to renal extracellular matrix damage in experimental diabetes. Diabetes [print-electronic]. 2015 Jun; 64(6): 2242-53. PMID: 25605804, PMCID: PMC4439565, PII: db14-1001, DOI: 10.2337/db14-1001, ISSN: 1939-327X.

Li L, Brown KL, Ma R, Stone MP. DNA Sequence Modulates Geometrical Isomerism of the trans-8,9- Dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)- 9-hydroxy Aflatoxin B1 Adduct. Chem. Res. Toxicol. 2015 Feb 2/16/2015; 28(2): 225-37. PMID: 25587868, PMCID: PMC4332041, DOI: 10.1021/tx5003832, ISSN: 1520-5010.

Stone MP, Huang H, Brown KL, Shanmugam G. Chemistry and structural biology of DNA damage and biological consequences. Chem. Biodivers. 2011 Sep; 8(9): 1571-615. PMID: 21922653, PMCID: PMC3714022, DOI: 10.1002/cbdv.201100033, ISSN: 1612-1880.

Banerjee S, Brown KL, Egli M, Stone MP. Bypass of aflatoxin B1 adducts by the Sulfolobus solfataricus DNA polymerase IV. J. Am. Chem. Soc [print-electronic]. 2011 Aug 8/17/2011; 133(32): 12556-68. PMID: 21790157, PMCID: PMC3154525, DOI: 10.1021/ja2015668, ISSN: 1520-5126.

Brown KL, Roginskaya M, Zou Y, Altamirano A, Basu AK, Stone MP. Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5'-GTgG-3' sequence: destabilization of two base pairs at the lesion site. Nucleic Acids Res [print-electronic]. 2010 Jan; 38(2): 428-40. PMID: 19892827, PMCID: PMC2811006, PII: gkp844, DOI: 10.1093/nar/gkp844, ISSN: 1362-4962.

Brown KL, Voehler MW, Magee SM, Harris CM, Harris TM, Stone MP. Structural perturbations induced by the alpha-anomer of the aflatoxin B(1) formamidopyrimidine adduct in duplex and single-strand DNA. J. Am. Chem. Soc. 2009 Nov 11/11/2009; 131(44): 16096-107. PMID: 19831353, PMCID: PMC2773149, DOI: 10.1021/ja902052v, ISSN: 1520-5126.

Brown KL, Basu AK, Stone MP. The cis-(5R,6S)-thymine glycol lesion occupies the wobble position when mismatched with deoxyguanosine in DNA. Biochemistry. 2009 Oct 10/20/2009; 48(41): 9722-33. PMID: 19772348, PMCID: PMC2761728, DOI: 10.1021/bi900695e, ISSN: 1520-4995.

Brown KL, Bren U, Stone MP, Guengerich FP. Inherent stereospecificity in the reaction of aflatoxin B(1) 8,9-epoxide with deoxyguanosine and efficiency of DNA catalysis. Chem. Res. Toxicol. 2009 May; 22(5): 913-7. PMID: 19301826, PMCID: PMC3141577, DOI: 10.1021/tx900002g, ISSN: 1520-5010.

Christov PP, Brown KL, Kozekov ID, Stone MP, Harris TM, Rizzo CJ. Site-specific synthesis and characterization of oligonucleotides containing an N6-(2-deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine lesion, the ring-opened product from N7-methylation of deoxyguanosine. Chem. Res. Toxicol. 2008 Dec; 21(12): 2324-33. PMID: 19053322, PMCID: PMC2701371, PII: 10.1021/tx800352a, DOI: 10.1021/tx800352a, ISSN: 0893-228X.

Brown KL, Adams T, Jasti VP, Basu AK, Stone MP. Interconversion of the cis-5R,6S- and trans-5R,6R-thymine glycol lesions in duplex DNA. J. Am. Chem. Soc [print-electronic]. 2008 Sep 9/3/2008; 130(35): 11701-10. PMID: 18681438, PMCID: PMC2646635, DOI: 10.1021/ja8016544, ISSN: 1520-5126.

Brown KL, Deng JZ, Iyer RS, Iyer LG, Voehler MW, Stone MP, Harris CM, Harris TM. Unraveling the aflatoxin-FAPY conundrum: structural basis for differential replicative processing of isomeric forms of the formamidopyrimidine-type DNA adduct of aflatoxin B1. J. Am. Chem. Soc. 2006 Nov 11/29/2006; 128(47): 15188-99. PMID: 17117870, PMCID: PMC2693076, DOI: 10.1021/ja063781y, ISSN: 0002-7863.