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Faculty Detail    
Name STEPHEN BARNES
 
Campus Address BBRB 711 Zip 2170
Phone  (205) 934-7117
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
Secondary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics 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
Secondary  Environmental Health Sciences  Environmental Health Sciences Professor
Secondary  Genetics   Genetics Chair Office 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
Primary  Pharmacology/Toxicology   Pharmacology/Toxicology Chair's Office 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 directed the NIH Metabolomics Training Workshop (2013-2018).

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 may be necessary.

Selected Publications 
Publication PUBMEDID
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.   
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.   
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.   
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.   
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.   
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.   
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   
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.   
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.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.   
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.   
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.   
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, 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.   
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.   
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.   
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   

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