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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
Kim, H., Deshane, J., Barnes, S., and Meleth, S. Proteomics analysis of the actions of grape seed extract in rat brain: Technologic and biologic implications for the study of the actions of psychoactive compounds. Life Sciences, 78: 2060-2065, 2006.   
Sarkar, P., Sarkar, S., Ramesh, V., Hayes, B.E., Thomas, R.L., Wilson, B.L., Kim, H., Barnes, S., Kulkarni, A., Pellis, N. and T. Ramesh, G.T. Proteomic analysis of mice hippocampus in simulated microgravity environment. Journal of Proteome Research, 5: 548-553, 2006.   
Liu, C., Yu, S. Zinn, K., Wang, J., Zhang, L., Jia, Y., Kappes, J.C., Barnes, S., Kimberly, R.P., Grizzle, W.E. and Zhang, H-G. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. Journal of Immunology, 176, 1375-1385, 2006.   
Horn-Ross, P.L., Barnes, S., Lee, V.S., Collins, C.N., Reynolds, P., Lee, M.M., Stewart, S.L., Canchola, A.J., Wilson, L., Jones, K. Reliability and Validity of an Assessment of Usual Phytoestrogen Consumption. Cancer Causes and Control, 17; 85-93, 2006.   
Huang, C.M., Wang, C.C., Kawai, M., Barnes, S., and Elmets, C.A. Surfactant sodium lauryl sulfate enhances skin vaccination: Molecular characterization via a novel technique using ultrafiltration capillaries and mass spectrometric proteomics. Mol Cell Proteomics 5: 523-530, 2006.   
Zakharkin S.O., Kim, K., Mehta, T., Chen, L., Barnes, S., Scheirer, K.E., Parrish, R.S., Allison, D.B., and Page, G.P. Sources of variation in Affymetrix microarray experiments. BMC Bioinformatics, 6:214, 2005.   
Meezan, E., Meezan, E.M., Jones, K., Moore II, D.R., Barnes, S., and Prasain, J.K. Contrasting effects of the isoflavones glucosides puerarin and daidzein on glucose metabolism in mice. Journal of Agricultural and Food Chemistry, 53: 8760-8767, 2005.   
Barnes, S., D’Alessandro, T., Kirk, M.C., Patel, R.P., Boersma, B.J., and Darley-Usmar, V.M. The importance of in vivo metabolism of polyphenols and their biological actions. In: “Phytochemicals – mechanisms of action”, Mesin, M.S., Bidlack, W.R., Davies, A.J., Lewis, D.S., Rudolph, R.K., CRC Press, Boca Raton, pp 51-59, 2003   
Kim, K., Page, G.P., Beasley, T. M., Barnes, S., Scheirer, K.E., and Allison, D.B. A proposed metric for assessing the measurement quality of individual microarrays. BMC Bioinformatics, 7: 35, 2006.   
Barnes, S., Prasain, J.K., Wang, C-C., Moore, D.R., II. Applications of LC-MS in the study of the uptake, distribution, metabolism and excretion of bioactive polyphenols from dietary supplements. Life Sciences, 78: 2054-2059, 2006.   
Huang, C.M., Wang, C-C., Kawai, M., Barnes, S., Elmets, C.A. In vivo protein sampling using capillary ultrafiltration semi-permeable hollow fiber and protein identification via mass spectrometry-based proteomics. J Chromatogr A, 1109: 144-151, 2006.   
Huang, C.M, Wang, C-C., Barnes, S., Elmets, C. In vivo detection of secreted proteins from wounded skin using capillary ultrafiltration probes and mass spectrometric proteomics. Proteomics 6: 5805-5814, 2006.   
Huang CM, Ananthaswamy HN, Barnes S, Ma Y, Kawai M, Elmets CA. Mass spectrometric proteomics profiles of in vivo tumor secretomes: Capillary ultrafiltration sampling of regressive tumor masses. Proteomics 6: 6107-6116, 2006.   
Prasain, J.K., Reppert, A., Jones, K., Moore, D.R., II, Barnes, S., and Lila, M.A. Isoflavones in Pueraria lobata cell cultures. Phytochemical Analysis, 18: 50-59, 2006.   
Prasain, J.K., Xu, J., Kirk, M., Smith, M., Sfakianos, J., and Barnes, S. Differential biliary excretion of genistein metabolites following intraduodenal and intravenous infusion of genistin in female rats. Journal of Nutrition, 136:2975-2979, 2006.   
Cheong, J.M.K., Martin, B.R., Jackson, G.J., Elmore, D., McCabe, G.P., Nolan, J.R., Barnes, S., Peacock, M., and Weaver, C.M. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose response study using a novel approach with 41Ca. Journal of Clinical Endocrinology & Medicine, 92: 577-582, 2007.   
Prasain, J., Peng, N., Acosta, E., Moore, D.R., Arabshahi, A., Meezan, E., Barnes, S., Wyss, J.M. Pharmacokinetic study of puerarin in rat serum by liquid chromatography tandem mass spectrometry. Biomedical Chromatography, 21:410-414, 2007.   
Ye, Y., Celia Quijano, C., Robinson, K.M., Ricart, K.C., Strayer, A.L., Shacka, J.J., Kirk, M., Barnes, S., Radi, R., Beckman, J.S., Estévez, A.G. Tyrosine nitration in peroxynitrite-induced apoptosis of motor neurons and PC12 cells. Journal of Biological Chemistry, 282: 6324-6337, 2007   
Chacko, B.K., Chandler, R.T., D’Alessandro, T.L., Mundhekar, A., Khoo, N.K., Botting, N., Barnes, S., Patel, R.P. Anti-inflammatory effects of isoflavones are dependent on flow and human endothelial cell PPARγ. Journal of Nutrition, 137: 351-356, 2007.   
Lee, S.A., Wen, W, Xiang, Y.B., Barnes, S., Liu, D.K., Cai, Q., Zheng, W., Shu, X.O. Assessment of dietary isoflavone intake among middle age Chinese men. Journal of Nutrition, 137: 1011-1016, 2007.   
Sites, C.K., Cooper, B.C., Toth, M.J., Gastaldelli, A.,Arabshahi, A. Barnes, S. Effect of a Daily Supplement of Soy Isoflavones on Body Composition and Insulin Secretion in Postmenopausal Women. Fertility and Sterility, in press, 2007.   
Brand, J.P.L., Beasley, T.M., Page, G.P., Bartolucci, A.A., Kim, K., Barnes, S., and Allison, D.B. An adaptive weighted p-value algorithm for more powerful multiplicity control in high dimensional biology: an application to inferential testing in microarray data analysis. Bioinformation, 1:384, 2007.   
Styles, N.A, Falany, J.L., Barnes. S., Falany. C.N. Quantification and Regulation of the Subcellular Distribution of Bile acid CoA:amino acid N-acyltransferase Activity in Rat Liver. Journal of Lipid Research, 48: 1305-1315, 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.   
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.   
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   
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 
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 
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 
Wang, C-C., Prasain, J., and Barnes, S. Methods used in the analysis of phytoestrogens. Journal of Chromatography, 777: 3-28, 2002.  12270197 
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 
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 
Belenky, M, Kim, H., Prasain, J., and Barnes, S. DING – a protein without a gene. J Nutr, 133: 2497S-2501S, 2003  12480230 
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 
Barnes, S. Phytoestrogens and osteoporosis – what is a safe dose? British Journal of Nutrition, 89: S101-S108, 2003.  12725659 
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 
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 
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 
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 
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 
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 
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 
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 
Kim, H., Page, G.P., and Barnes, S. Proteomics and mass spectrometry in nutrition research. Nutrition, 20: 155-165, 2004.  14698031 
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 
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. Soy isoflavones: phytoestrogens and what else? Journal of Nutrition 134: 1225S-1228S, 2004  15113976 
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 
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 
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 

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