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Faculty Detail    
Name STEPHEN BARNES
 
Campus Address MCLM 452 Zip 0005
Phone  (20-5) -117
E-mail  sbarnes@uab.edu
Other websites
     

Education
Undergraduate  University of Surrey, UK      BSc (honors in applied chemistry) 
Graduate  Imperial College, University of London, UK      PhD in Biochemistry 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pharmacology/Toxicology   Pharmacology/Toxicology Chair's Office Professor
Secondary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Secondary  Environmental Health Sciences  Environmental Health Sciences Professor
Secondary  Genetics   Genetics Chair Office Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor
Center  General Clinical Research Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor
Center  Vision Sciences (Org-Ret)  Vision Science Research Center (Org-Ret) Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 

Biographical Sketch 
Dr. Barnes was educated in England, receiving a BSc in Applied Chemistry from the University of Surrey in 1967, UK, and a PhD in Biochemistry (mentor: Sir Ernst Boris Chain), Imperial College, London, UK, 1972. His postdoctoral training was in the Academic Department of Medicine (mentor: Dame Sheila Sherlock), Royal Free Hospital, London, UK. In 1977, Dr. Barnes joined UAB in the Division of Gastroenterology and has risen through the ranks to full professor in the Departments of Pharmacology & Toxicology (Primary) and Biochemistry & Molecular Genetics, Environmental Health Sciences, Forensic Sciences, Genetics and Vision Sciences. He is the author of 268 refereed publications and 25 book chapters. He was the Co-Director of the Purdue-UAB Botanical Center for Age-Related Disease (2000-2010) and Director of the Center for Nutrient-Gene Interaction in Cancer Prevention (2003-2010). He served on the National Advisory Council of the Center for Alternative and Complementary Medicine from 2007-2010 and the NIH Council of Councils from 2009-2012. Currently, he is the Director of the UAB Targeted Metabolomics and Proteomics Laboratory and directs the NIH Metabolomics Training Workshop.

Society Memberships
Organization Name Position Held Org Link
American Association for the Advancement of Science    http://www.aaas.org 
American Society for Mass Spectrometry    http://www.asms.org 



Research/Clinical Interest
Title
Bile acids, polyphenols and metabolism, and their effects on protein expression and function in chronic disease
Description
There are two strong themes in Dr. Barnes’ lab: (1) the biochemistry, chemistry and molecular biology of the enzymes responsible for the formation of bile acid-amino acid conjugates; and (2) the mechanisms of dietary prevention of chronic diseases such as cancer, lens cataracts and atherosclerosis. In each projects, extensive use is made of mass spectrometry techniques. In the bile acid project, we have been carrying site-directed mutagenesis of bile acid CoA:amino acid N-acyltransferase (BAT) to identify the amino acid residues that are critical for its activity. Those for the first step in enzyme catalysis have been defined (see Sfakianos et al. below). A new project is to identify the residues that account for the marked differences in utilization of the amino acid substrates (glycine and taurine) between BATs from different species. Aligned with this project is an opportunity to investigate the structure of BATs both in the crystalline (X-ray Crystallography) and solution states (H-D exchange using mass spectrometry). In collaboration with UCSF and the University of New Jersey School of Medicine and Dentistry, an important mutation in BAT has been uncovered that leads to its inactivation – it is manifested as pediatric cholestasis and delayed growth in the children in the Pennsylvania Amish community. The diet-chronic disease research is based on the roles of dietary polyphenols. These undergo modifications at sites of inflammation, producing novel pharmacophores. The polyphenols also alter posttranslational modifications of proteins at these sites and target key cellular proteins such as the estrogen receptors and DING (see below). A newly funded project is the role of polyphenols on UV light-induced protein modifications to the lens proteins of the eye. We are using mass spectrometry to identify the metabolites, the protein targets, and the chemical nature of novel types and sites of protein modifications. New projects are focused on identifying the cellular mechanisms that polyphenols and their metabolites target. An affinity approach has revealed a protein from human breast cancer MCF-7 cells that has no gene partner, suggesting that revisions of the DNA-RNA-protein paradigm are necessary.

Selected Publications 
Publication PUBMEDID
Harper VM, Oh JY, Stapley R, Marques MB, Wilson L, Barnes S, Sun CW, Townes T, Patel RP. Peroxiredoxin-2 recycling is inhibited during erythrocyte storage. Antioxid Redox Signal. 2015 Feb 1;22(4):294-307.  25264713 
Nakatsu CH, Armstrong A, Clavijo AP, Martin BR, Barnes S, Weaver CM. Fecal bacterial community changes associated with isoflavone metabolites in postmenopausal women after soy bar consumption. PLoS One. 2014 Oct 1;9(10):e108924.   25271941 
Kramer PA, Chacko BK, Ravi S, Johnson MS, Mitchell T, Barnes S, Arabshahi A, Dell'Italia LJ, George DJ, Steele C, George JF, Darley-Usmar VM, Melby SJ. Hemoglobin-associated oxidative stress in the pericardial compartment of postoperative cardiac surgery patients. Lab Invest. 2015 Feb;95(2):132-41.  25437645 
Lopez EF, Kabarowski JH, Ingle KA, Kain V, Barnes S, Crossman DK, Lindsey ML, Halade GV. Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction. Am J Physiol Heart Circ Physiol. 2015 Feb 15;308(4):H269-80.  25485899 
Wheeler, J.B., Shaw, D.R. and S. Barnes. Purification and characterization of bile acid CoA synthetase from rat liver. Archives of Biochemistry and Biophysics, 348: 15-24, 1997.  9390170 
Crow, J., Y-Z Ye, M. Strong, S. Barnes, M. Kirk and J. Beckman. Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head of neurofilament-L. Journal of Neurochemistry, 69: 1945-1953, 1997.  9349539 
Falany, C.N., H. Fortinberry, E.H. Leiter, and S. Barnes. Cloning and expression of mouse liver bile acid CoA: amino acid N-acyltransferase. Journal of Lipid Research, 38: 86-95, 1997.  9215542 
Sfakianos, J., L. Coward, M. Kirk and S. Barnes. Intestinal uptake and biliary excretion of the isoflavone genistein in the rat. Journal of Nutrition, 127: 1260-1268, 1997.  9202077 
Kaput J, Ordovas JM, Ferguson L, van Ommen B, Rodriguez RL, Allen L, Ames BN, Dawson K, German B, Krauss R, Malyj W, Archer MC, Barnes S, Bartholomew A, Birk R, van Bladeren P, Bradford KJ, Brown KH, Caetano R, Castle D, Chadwick R, Clarke S, Clement K, Cooney CA, Corella D, Manica da Cruz IB, Daniel H, Duster T, E Ebbesson SO, Elliott R, Fairweather-Tait S, Felton J, Fenech M, Finley JW, Fogg-Johnson N, Gill-Garrison R, Gibney MJ, Gillies PJ, Gustafsson JA, Hartman Iv JL, He L, Hwang JK, Jais JP, Jang Y, Joost H, Junien C, Kanter M, Kibbe WA, Koletzko B, Korf BR, Kornman K, Krempin DW, Langin D, Lauren DR, Ho Lee J, Leveille GA, Lin SJ, Mathers J, Mayne M, McNabb W, Milner JA, Morgan P, Muller M, Nikolsky Y, van der Ouderaa F, Park T, Pensel N, Perez-Jimenez F, Poutanen K, Roberts M, Saris WH, Schuster G, Shelling AN, Simopoulos AP, Southon S, Tai ES, Towne B, Trayhurn P, Uauy R, Visek WJ, Warden C, Weiss R, Wiencke J, Winkler J, Wolff GL, Zhao-Wilson X, Zucker JD. The case for strategic international alliances to harness nutritional genomics for public and personal healthdagger. Br J Nutr. 2005 Nov;94(5):623-632.   16277761 
Meezan E, Meezan EM, Jones K, Moore R, Barnes S, Prasain JK. Contrasting effects of puerarin and daidzin on glucose homeostasis in mice. J Agric Food Chem. 2005 Nov 2;53(22):8760-7.   16248582 
Yang X, Wang J, Liu C, Grizzle WE, Yu S, Zhang S, Barnes S, Koopman WJ, Mountz JD, Kimberly RP, Zhang HG. Cleavage of p53-vimentin complex enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of rheumatoid arthritis synovial fibroblasts. Am J Pathol. 2005 Sep;167(3):705-19.  16127151 
Zakharkin SO, Kim K, Mehta T, Chen L, Barnes S, Scheirer KE, Parrish RS, Allison DB, Page GP. Sources of variation in Affymetrix microarray experiments.
BMC Bioinformatics. 2005 Aug 29;6:214.  
16124883  
Prasain JK, Moore R, Hurst JS, Barnes S, van Kuijk FJ. Electrospray tandem mass spectrometric analysis of zeaxanthin and its oxidation products. J Mass Spectrom. 2005 Jul;40(7):916-23.  15934038 
Hedlund TE, Maroni PD, Ferucci PG, Dayton R, Barnes S, Jones K, Moore R, Ogden LG, Wahala K, Sackett HM, Gray KJ. Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men. J Nutr. 2005 Jun;135(6):1400-6.   15930444 
Uppala PT, Roy SK, Tousson A, Barnes S, Uppala GR, Eastmond DA. Induction of cell proliferation, micronuclei and hyperdiploidy/polyploidy in the mammary cells of DDT- and DMBA-treated pubertal rats. Environ Mol Mutagen. 2005 Jul;46(1):43-52.  15880734 
Barnes S, Prasain J. Current progress in the use of traditional medicines and nutraceuticals. Curr Opin Plant Biol. 2005 Jun;8(3):324-8.  15860430 
Cai DJ, Zhao Y, Glasier J, Cullen D, Barnes S, Turner CH, Wastney M, Weaver CM. Comparative effect of soy protein, soy isoflavones, and 17beta-estradiol on bone metabolism in adult ovariectomized rats. J Bone Miner Res. 2005 May;20(5):828-39. Epub 2004 Dec 27.   15824856 
Chacko BK, Chandler RT, Mundhekar A, Khoo N, Pruitt HM, Kucik DF, Parks DA, Kevil CG, Barnes S, Patel RP. Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions. Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H908-15. Epub 2005 Apr 1.  15805228 
Allison DB, Cutter G, Poehlman ET, Moore DR, Barnes S. Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain? Int J Obes (Lond). 2005 Apr;29(4):443-6.   15700046  
Deshane J, Chaves L, Sarikonda KV, Isbell S, Wilson L, Kirk M, Grubbs C, Barnes S, Meleth S, Kim H. Proteomics analysis of rat brain protein modulations by grape seed extract. J Agric Food Chem. 2004 Dec 29;52(26):7872-83.   15612770 
Kim H, Hall P, Smith M, Kirk M, Prasain JK, Barnes S, Grubbs C. Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent. J Nutr. 2004 Dec;134(12 Suppl):3445S-3452S.   15570052  
Prasain JK, Wang CC, Barnes S. Mass spectrometric methods for the determination of flavonoids in biological samples. Free Radic Biol Med. 2004 Nov 1;37(9):1324-50.  15454273 
Huang CM, Elmets CA, van Kampen KR, Desilva TS, Barnes S, Kim H, Tang DC. Prospective highlights of functional skin proteomics. Mass Spectrom Rev. 2005 Sep-Oct;24(5):647-60.  15376279 
Isom, A.I., Wilson, L., Kirk, M., Coward, L., Darley-Usmar, V.M. and Barnes, S. Modification of cytochrome c by 4-hydroxy-2-nonenal: evidence for histidine, lysine and arginine-aldehyde adducts. Journal of American Society of Mass Spectrometry 15: 1136-1147, 2004.   15276160 
Prasain, J.K., Jones, K., Brissie, N., Moore, D.R. II, Wyss, J.M., Barnes, S. Identification of puerarin and its metabolites in rats by liquid chromatography-tandem mass spectrometry. Journal of Agricultural Food Chemistry, 52: 3708-3712, 2004.  15186086 
Zafar TA, Weaver CM, Jones K, Moore DR 2nd, Barnes S. Inulin effects on bioavailability of soy isoflavones and their calcium absorption enhancing ability. Journal of Agricultural Food Chemistry 52:2827-2831, 2004.  15137821 
Barnes, S. Soy isoflavones: phytoestrogens and what else? Journal of Nutrition 134: 1225S-1228S, 2004  15113976 
Schuler, A.M., Barnes, S., Gower, B.A., and Wood, P.A. Role of dietary phytoestrogens on cold tolerance in long-chain acyl-CoA dehydrogenase deficient mice. Journal of Nutrition, 134: 1028-1031, 2004.  15113940 
Barnes, S., and Kim, H. Nutriproteomics: Identifying the molecular targets of nutritive and non-nutritive components of the diet. Journal of Biochemistry and Molecular Biology 37:59-74, 2004.  14761304 
Kim, H., Page, G.P., and Barnes, S. Proteomics and mass spectrometry in nutrition research. Nutrition, 20: 155-165, 2004.  14698031 
Boersma, B.J., D’Alessandro, T., Benton, M.R., Kirk, M., Wilson, L.S., Prasain, J., Botting, N.P., Barnes, S., Darley-Usmar, V.M. and Patel, R.P. Neutrophil myeloperoxidase chlorinates soy isoflavones and enhances their antioxidant properties. Free Radical Biology and Medicine, 35:1417-1430, 2003.  14642389 
Boersma, B.J., Patel, R.P., Benton, M.R., Kirk, M., Wilson, L.S., Botting, N.P., Barnes, S., and Darley-Usmar, V.M. Neutrophil myeloperoxidase chlorinates soy isoflavones and enhances their antioxidant properties. Free Radical Biology and Medicine, 35:1417-1430, 2003.  14642389 
Page G.P., Edwards J.W., Barnes S., and Allison, D.B. A Design & Statistical Perspective on Microarray Gene. Expression Studies in Nutrition – the need for playful creativity and scientific hard-mindedness. Nutrition, 19: 997-1000, 2003.  14624952 
D’Alessandro, T., Prasain, J., Botting, N.P, Moore, R., Darley-Usmar, V.M., Patel, R.P., and Barnes, S. Polyphenols, Inflammatory Response, and Cancer Prevention: Chlorination of Isoflavones by Human Neutrophils. J Nutr,133:3773S-3777S, 2003.  14608113 
He, D., Barnes, S, Falany, C.N. Rat Liver Bile Acid CoA: Amino Acid N-acyltransferase: Expression, Characterization and Peroxisomal Localization J Lip Res, on line September 1, 2003.  12951368 
Carballal, S., Radi, R., Kirk, M.C., Barnes, S., Freeman, B.A. and Alvarez, B. Sulfenic acid formation in human serum albumin by hydrogen peroxide and peroxynitrite. Biochemistry, 42: 9906-9914, 2003.  12924939 
Prasain, J.K., Boersma, B.J., Kirk, M., Wilson, L., Patel, R., Darley-Usmar, V.M., Botting, N. and Barnes, S. ESI-tandem Mass Spectrometric Analysis of Chlorinated and Nitrated Isoflavones. J Mass Spect, 38: 764-771, 2003  12898636 
Prasain, J.K., Jones, K., Kirk, M., Wilson, L., Smith-Johnson, M., Weaver, C.M., Barnes, S. Identification and quantitation of isoflavonoids in Kudzu Dietary Supplements by HPLC and electrospray ionization tandem mass spectrometry. J Agric Food Chem, 51:4213-4218, 2003  12848487 
Barnes, S. Phytoestrogens and osteoporosis – what is a safe dose? British Journal of Nutrition, 89: S101-S108, 2003.  12725659 
Lanman, J., Lam, T., Barnes, S., Sakalian, M., Emmett, M.R., Marshall, A.G., and Prevelige, P.E., Jr. Identification of novel interactions in HIV-1 capsid protein assembly by high resolution mass spectrometry. Journal of Molecular Biology, 325:759-772, 2003.  12507478 
Belenky, M, Kim, H., Prasain, J., and Barnes, S. DING – a protein without a gene. J Nutr, 133: 2497S-2501S, 2003  12480230 
Falany, C.N., Xie, X, Wheeler, J.B., Wang, J., Smith, M., He, D., and Barnes, S. Molecular cloning and expression of rat liver bile acid CoA ligase. Journal of Lipid Research, 43: 2062-2071, 2002.  12454267 
Aslan, M, Barnes, S., Kirk, M, Rosenfeld, S, Townes, T, Ryan, T and BA Freeman. Nitric oxide-dependent generation of reactive species in sickle cell disease: renal and hepatocellular actin tyrosine nitration. Journal of Biological Chemistry, 278: 4194-4204, 2003.  12401783 
Wang, C-C., Prasain, J., and Barnes, S. Methods used in the analysis of phytoestrogens. Journal of Chromatography, 777: 3-28, 2002.  12270197 
Sfakianos, M., Wilson, L., Sakalian, M., Falany, C.N., and Barnes, S. Conserved Residues in the Putative Catalytic Triad of Human Bile Acid Coenzyme A: Amino Acid N-acyltransferase. Journal of Biological Chemistry, 277: 47270-47275, 2002.  12239217 
King, L. III, S. Barnes, U. Glufke, M.E. Henz, M. Kirk, K.A. Merkler, J.C. Vederas, B.J. Wilcoz, and D.J. Merkler. The enzymatic formation of novel bile acid primary amides. A possible class of new mammalian hormones. Archives of Biochemistry and Biophysics, 374: 107-117, 2000.  10666288 
Boersma, B.J., Patel, R.P., Kirk, M., Darley-Usmar, V.M. and S. Barnes. Chlorination and Nitration of Soy Isoflavones. Archives of Biochemistry & Biophysics, 368: 265-275, 1999.  10441377 
Ashwell, M., Stone, E., Mathers, J., Barnes, S., Compston, J., Francis, R.M., Key, T., Cashman, K.D., Cooper, C., Khaw, K.T., Lanham-New, S., Macdonald, H., Prentice, A., Shearer, M. and Stephen, A. Nutrition and bone health projects funded by the UK Food Standards Agency: have they helped to inform public health policy? British Journal of Nutrition, in press, 2007   
Kim H, Eliuk S, Deshane J, Meleth S, Sanderson T, Pinner A, Robinson G, Wilson L, Kirk M, Barnes S. 2D gel proteomics: an approach to study age-related differences in protein abundance or isoform complexity in biological samples. Methods in Molecular Biology 371:349-391, 2007.   
Zhang, H-G., Kim, H., Liu, C., Yu, S., Wang, J, Zhang, L., Grizzle, W.E., Kimberly, R.P., and Barnes, S. Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. Biochimica et Biophysica Acta, 1773: 1116-1123, 2007.   

Keywords
bile acids, isoflavonoids and polyphenols, metabolomics, proteomics, mass spectrometry