Roles of regulatory post-translational modifications, in particular O-glycosylation, in increasing functional diversity of proteins.

E-mail: lwells@ccrc.uga.edu
Telephone: 706-542-7806
Fax: 706-542-4412

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Using a combination of methodologies, including mass spectrometry, protein biochemistry, cell biology, genetics, proteomics, and molecular biology, we study the role of PTMs (primarily O-glycosylation) in a variety of pathophysiological processes including cancer, diabetes, and congenital muscular dystrophy. Our research is aimed at increasing our understanding of how increased functional diversity leads to finer control of biological processes. The hope is that by understanding the role of PTMs, we will not only more accurately describe fundamental biological processes but will also elucidate novel therapeutic targets in disease states such as type II diabetes, congenital muscular dystophy and cancer in which these processes have become dysregulated.

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Journal Articles
Book Chapters are listed at the bottom of this page.

P. Zhao, A.V. Nairn, S. Hester, K.W. Moremen, R.M. ORegan, G. Oprea, L. Wells, M. Pierce, K.L. Abbott. 2012. Proteomic identification of glycosylphosphatidylinositol anchor-dependent membrane proteins elevated in breat carcinoma. J.Biol Chem. 287: 25230-25240. PMID:22654114

A.V. Nairn, K. Aoki, M. Dela Rosa, M. Porterfield, J.M. Lim, M. Kulik, J.M. Pierce, L. Wells, S. Dalton, M. Tiemeyer, K.W. Moremen. 2012. Regulation of glycan structures in murine embryonic stem cells: COMBINED TRANSCRIPT PROFILING OF GLYCAN-RELATED GENES AND GLYCAN STRUCTURAL ANALYSIS. J. Biol. Chem. 287: 37835-37856. PMID:22988249

J.K. Lee, R.T. Matthews, J.M. Lim, K. Swanier, L. Wells, J.M. Pierce. 2012. Developmental expression of the neuron-specific N-caetylglucosaminyltransferase Vb (GnT-Vb/lX) and identification of its in vivo glycan products in comparison with those of its paralog, GnT-V . J.Biol. Chem. 287: 28526-28536. PMID:22715095

J.J. Fong, B.L. Nguyen, R. Bridger, E.E. Medrano, L. Wells, S. Pan, R.N. Sifers. 2012. O-GlcNAc is a novel regulator of mitosis-specific phosphorylations on histone H3. J.Biol. Chem. 287: 12195-12203. PMID:22371497

D.T. Tran, J.M. Lim, M. Liu, S.H. Stainaker, L. Wells, K.G. Ten Hagen, D. Live. 2012. Glycosylation of alpha-dystroglycan: O-mannosylation influences the subsequent addition of GalNAc by ppGalNAcTs. J. Biol. Chem. 287: 20967-20974. PMID:22549772

P. Zhao, R. Viner, C.F. Teo, G.J. Boons, D. Horn, L. Wells. 2011. Combining high-energy C-trap dissociation and electron transfer dissociation for protein O-GlcNAc modification site assignment. J. Proteome Res. 10: 4088-4104.

K. Mo, T. Fang, S. Stainaker, P.S. Kirby, M. Liu, L. Wells, M. Pierce, D.H. Live, G.J. Boons. 2011. Synthetic, structural and biosynthetic studies of an unusual phosphoglycopeptide derived from α-dystroglycan. J. Am. Chem. Soc. 133: 14418-14430.

S.H. Stainaker, R. Stuart, L. Wells. 2011. Mammalian O-mannosylation: unvolved questions of structure/function. Curr. Opin. Struct. Biol. 21: 603-609. PMID:21945038

J. Barnes, J.M Lim, A. Godard, F. Blanchard, L. Wells, R. Steet. 2011. Extensive mannose phosphorylation on leugemic inhibitory factor (LIF)controls its extracellular levels by multiple mechanisms. J. Biol. Chem. 286: 24855-24864. PMID:21613225

S.H. Stainaker, K. Aoki, J.M. Lim, M. Porterfield, M. Liu, J.S. Satz, S. Buskirk, Y. Xiong, P. Zhang, K.P. Campbell, H. Hu, D. Live, M. Tiemeyer, L. Wells. 2011. Glycomic analyses of mouse models of congenital muscular dystrophy. J. Biol. Chem. 286: 21180-21190. PMID:21460210

C.F. Teo, E.E. Wollaston-Hayden, L. Wells. 2010. Hexosamine flux, the O-GlcNAc modification, and the development of insulin resistance in adipocytes. Mol. Cell. Endocrinol. 318: 44-53. PMID:19799964

S. Brimble, E.E. Wollaston-Hayden, C.F. Teo, A.C. Morris, L. Wells. 2010. The role of the O-GlcNAc modification in regulating eukaryotic gene expression. Curr. Signal Transduc. Ther. 5: 12-24.

T. Yoshida-Moriguchi, S. Davis, S. Hammond, L. Yu, S. Kunz, M. Madson, M.B.A. Oldstone, H. Schacter, L. Wells, K.P. Campbell. 2010. O-mannosyl phosphorylation of slpha-dystroglycan: A novel modification required for laminin-binding. Science 327: 88-92. PMID:20044576

M.A. Humbard, H.V. Miranda, J.M. Lim, D.J. Krause, J.R. Pritz, G.K. Zhou, S. Chen, L. Wells, J.A. Maupin-Farlow. 2010. Ubiquitin-like Small Archaeal Modifier Proteins (SAMPs) in Haloferaz volcanii. Nature 463: 54-60. PMID:20054389

N. Nakamura, S.H. Stainaker, D. Lyalin, O. Lavrova, L. Wells, V.M. Panin. 2010. Drosophila dystroglycan is a target of O-mannosyltransferase activity of two protein O-mannosyltransferases, Rotated Abdomen and Twisted. Glycobiology 20: 381-394. PMID:19969597

C.F. Teo, S. Ingale, G.A. Elsayed, M.A. Wolfert, L. Wells, G.J. Boons. 2010. Generation of O-GlcNAc specific monoclonal antibodies using a novel synthetic immunogen. Nature Chem. Biol. 6: 338-343. PMID:20305658

S.H. Stalnaker, S. Hashmi, J-M Lim, K. Aoki, M. Porterfield, G. Gutierrez-Sanchez, J. Wheeler, J.M. Ervasti, C. Bergmann, M. Tiemeyer, L. Wells. 2010. Site-mapping and characterization of O-glycan structures on alpha-dystroglycan isolated from rabbit skeletal muscle. J. Biol. Chem. 285: 24882-24891. PMID:20507986

S.H. Stalnaker, S. Hashmi, J-M Lim, K. Aoki, M. Porterfield, G. Gutierrez-Sanchez, J. Wheeler, J.M. Ervasti, C. Bergmann, M. Tiemeyer, L. Wells. 2010. Site-mapping and characterization of O-glycan structures on alpha-dystroglycan isolated from rabbit skeletal muscle. J. Biol. Chem. 285: 24882-24891. PMID:20507986

K.L. Abbott, J. Lim, L. Wells, B.B. Benigno, J.F. McDonald, M. Pierce. 2010. Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis. Proteomics 10: 470-481. PMID:19953551

R. Orlando, J.M. Lim, J.A. Atwood, P.M. Angel, M. Feng, G. Alvarez-Manilla, K.W. Moremen, W.S. York, M. Tiemeyer, J.M. Pierce, S. Dalton, R.L. Wells. 2009. IDAWG: Metabolic incorporation of stable isotope labels for quantitative glycomics of cultured cells. J. Proteome Res. 8: 3816-3823. PMID:19449840

Y. Li, C. Cao, W. Jia, L. Yu, M. Lemonnier, Q. Wang, Y. Huang, J.M. Lim, M. Ishihara, L. Wells, P. Azadi, H. Robinson, Y.W. He, L. Zhang, R.A. Mariuzza. 2009. Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule. EMBO J. 28: 286-297. PMID:19153605

J.M. Lim, K. Aoki, P.M. Angel, D. Garrison, D. King, M. Tiemeyer, C. Bergmann, L. Wells. 2009. Mapping glycans onto specific N-linked glycosylation sites of Pyrus communis PGIP redefines the interface for EPG-PGIP interactions. J. Proteome Res. 8: 673-680. PMID:19072240

D.M. Webster, C.F. Teo, Y. Sun, D. Sloga, S. Gay, K.D. Sklonowski, L. Wells, S.T. Dougan. 2009. O-GlcNAc modifications regulate cell survival and epiboly during zebrafish development. BMC Develop. Biol. 9: 28-. PMID:19383152

C.R. Hale, P. Zhao, S.K. Olson, M.O. Duff, B.R. Gravely, L. Wells, R.M. Terns, M.P. Terns. 2009. RNA-guided RNA cleavage by a CRISP RNA-Cas protein complex. Cell 139: 945-956. PMID:19945378

K.L. Abbott, J.-M. Lim, R.L. Wells, B.B. Benigno, J.F. McDonald, J.M. Pierce. 2009. Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis. Proteomics 10: 470-481. PMID:19953551

K.L. Abbott, K. Aoki, J.-M. Lim, M. Porterfield, R. Johnson, R.M. O'Regan, L. Wells, M. Tiemeyer, M. Pierce. 2008. Targeted glycoproteomic identification of biomarkers for human breast carcinoma. J. Proteome Res. 7: 1470-1480. PMID:18271524

J. Lim, D. Sherling, C.F. Teo, D. Hauseman, D. Lin, L. Wells. 2008. Defining the regulated secreted proteome of rodent adipocytes upon the induction of insulin resistance. J. Proteome Res. 7: 1251-1263. PMID:18237111

N. Scholler, J.A. Gross, B. Garvik, L. Wells, Y. Liu, C.M. Loch, A.B. Ramirez, M.W. McIntoch, P.D. Lampe, N. Urban. 2008. Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery. J. Transl. Med. 6: 41-52. PMID:18652693

P.M. Angel, J.M. Lim, L. Wells, C. Bergmann, R. Orlando. 2007. A potential pitfall in 18O-based N-linked glycosylate site mapping. Rapid Commun. Mass Spectrom. 21: 674-682. PMID:17279607

Y. Akimoto, G.W. Hart, L. Wells, K. Vosseller, K. Yamamoto, E. Munetomo, M. Ohara-Imaizumi, C. Nishiwaki, S. Nagamatsu, H. Hirano, H. Kawakami. 2007. Elevation of the post-translational modification of proteins by O-GlcNAc leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic GK rats. Glycobiology 17: 127-140. PMID:17095531

K. Aoki, M. Perlman, J.M. Lim, R. Cantu, L. Wells, M. Tiemeyer. 2007. Dynamic developmental elaboration of N-linked glycan complexity in the Drosophila melanogaster embryo. J. Biol. Chem. 282: 9127-9142. PMID:17264077

K. Koles, J.M. Lim, K. Aoki, M. Porterfield, M. Tiemeyer, L. Wells, V. Panin. 2007. Identification of N-glycosylated proteins from the central nervous system of Drosophila melanogaster. Glycobiology 17: 1388-1403. PMID:17893096

L. Wells. 2007. A QUICK look at O-GlcNAc dynamics. Nature Chem. Biol. 3: 303-304. PMID:17510643

T.G. Smith, J.M. Lim, M.V. Weinberg, L. Wells, T.R. Hoover. 2007. Direct analysis of the extracellular proteome from two strains of Helicobacter phlori. Proteomics 7: 2240-2245. PMID:17533641

N.G. Starostina, J.-M. Lim, M. Schvarzastein, L. Wells, A.M. Spence, E.T. Kipreos. 2007. A Cuil-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to regulate C. elegans sex determination. Develop. Cell 13: 127-139. PMID:17609115

M. Fakhouri, M. Elalayi, D. Sherling, J.D. Hall, E. Miller, X. Sun, L. Wells, E.K. LeMosy. 2006. Minor proteins and enzymes of the Drosophila eggshell matrix. Dev. Biol. 293: 127-141. PMID:16515779

B.D. Woosley, M. Xie, L. Wells., R. Orlando, D. Garrison, D. King, C. Bergmann. 2006. Comprehensive glycan analysis of recombinant Aspergillus niger-endo-polygalacturonase C. Anal. Biochem. 354: 43-53. PMID:16697346

B.D. Woosley, Y.H. Kim, V.S. Kumar, L. Wells, D. King, R. Poe, R. Orlando, C. Bergmann. 2006. Complete glycan analysis of recombinant Aspergillus niger endo-polygalacturonase A. Carbohydr. Res. 341: 2370-2378. PMID:16854399

K. Vosseller, K.C. Hansen, R.J. Chalkley, J.C. Trinidad, L. Wells, G.W. Hart, A.L. Burlingame. 2005. Quantitative analysis of both protein expression and serine/threonine post-translational modifications through stable isotope labeling with dithiothreitol. Proteomics 5: 388-398. PMID:15648052

Y. Akimoto, K. Yamamoto, E. Munetomo, L. Wells, K. Vosseller, G.W. Hart, H. Kawakami, H. Hirano. 2005. Elevated O-GlcNAc modification of proteins in various tissues of diabetic Goto-Kakizaki rats accompanied by diabetic complications. Acta Histochem. Cytochem. 38: 131-142.

L. Wells, L.K. Kreppel, F.I. Comer, B.E. Wadzinski, G.W. Hart. 2004. O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits. J. Biol. Chem. 279: 38466-38470. PMID:15247246

M.E. Drew, J.C. Morris, Z. Wang, L. Wells, M. Sanchez, S.M. Landfear, P.T. Englund. 2003. The adenosine analog tuberciden inhibits glycolysis in Trypanosoma brucei as revealed by an RNA interference library. J. Biol. Chem. 278: 46596-46600. PMID:12972414

L. Wells, G.W. Hart. 2003. O-GlcNAc turn twenty: functional implications for post-translational modification of nuclear and cytosolic proteins with a sugar. FEBS Lett. 546: 154-158. PMID:12829252

L. Wells, K. Vosseller, G.W. Hart. 2003. A role for N-acetylglucosamine s a nutrient sensor and mediator of insulin resistance. Cell. Mol. Life Sci. 60: 222-228. PMID:12678487

L. Wells, S.A. Whelan, G.W. Hart. 2003. O-GlcNAc: a regulatory post-translational modification. Biochem. Biophys. Res. Commun. 302: 435-441. PMID:12615051

L. Wells, K. Vosseller, R.N. Cole, J.M. Cronshaw, M.J. Matunis, G.W. Hart. 2002. Mapping sites of O-GlcNAc modification using affinity tags for serine and threonine post-translational modifications. Mol. Cell Proteomics 1: 791-804. PMID:12438562

K. Vosseller, L. Wells, M.D. Lane, G.W. Hart. 2002. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. USA 16: 5313-5318. PMID:11959983

K. Vosseller, K. Sakabe, L. Wells, G.W. Hart. 2002. Diverse regulation of protein function by O-GlcNAc, a nuclear and cytoplasmic carbohydrate post-translational modification. Curr. Opin. Chem. Biol. 6: 851-857. PMID:12470741

Book Chapters

L. Wells. 2009. O-glycan complexity and analysis (R.D. Cummings and J.M. Pierce, eds.). In: Handbook of Glycobiology, pp. 45-57. Academic Press.

R.J. Chalkey, L. Wells, K. Vosseller. 2008. O-GlcNAc Proteomics. In: Mass Spectrometry Analysis of Proteins in the Series Comprehensive Analytical Chemistry Elsevier, In press.

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