Assistant Professor of Biochemistry and Molecular Biology Adjunct Assistant Professor of Chemistry Georgia Cancer Coalition Scholar Office: 3018 CCRC Contact Phone Number: 542-7806 Lab: 3018 CCRC Lab Phone: 542-7806 E-mail: lwells@ccrc.uga.edu Additional Information / Lab Page

Brief Biography

Dr. Wells received his B.S. in Chemistry, with a minor in Psychology, in 1991 from the Georgia Institute of Technology, and after spending two years working at the Microchemical Facility, his Ph.D. in Biochemistry and Molecular Biology in 1998 from the Emory University School of Medicine. A postdoctoral research fellowship at the Johns Hopkins School of Medicine in Biological Chemistry followed, which was supported by a National Research Service Award from the National Cancer Institute of the NIH. Dr. Wells joined the CCRC in August of 2003.

Research Interests

Our broad research interest is in understanding how post-translational modifications modulate the properties of proteins. Specifically, we study "nutrient sensing" by characterizing the enzymes O-GlcNAc transferase, O-GlcNAcase, mTOR (mammalian target of Rapamycin, a ser-thr kinase), and AMP-activated protein kinase in mammalian cell culture and animal tissues. These enzymes have been implicated in responding to nutrients and regulating signal transduction cascades.

Using a combination of methodologies, including mass spectrometry, protein biochemistry, cell biology, proteomics, and molecular biology, we plan to further elucidate the mechanisms by which cells recognize their environment. Our research is aimed at building on a model in which cells are not blindly responding to extracellular stimuli but instead are taking into account their own nutritional states and then responding appropriately. The goal is that elucidation of this model will help to convert a simple "ON/OFF" Newtonian model of extracellular stimuli-mediated signal transduction into a quantum probability model of cells integrating both extra- and intracellular signaling information before responding to environmental cues. The hope is that this paradigm shift will not only more accurately describe fundamental biological processes but will also elucidate novel therapeutic targets in disease states such as type II diabetes and cancer.

Selected Recent Publications

Shafer, W.M., M.E. Shepard, B. Boltin, L. Wells, and J. Pohl. 1993. Synthetic peptides of human lysosomal cathepsin G with potent antipseudomonal activity. Infect. Immun. 61: 1900-1908.

Fridovich-Keil, J.L., B.B. Quimby, L. Wells, L.A. Mazur, and J.P. Elsevier. 1995. Characterization of the N314D allele of human galactose-1-phosphate uridylyltransferase using a yeast expression system. Biochem. Mol. Med. 56: 121-130.

Elsevier, J.P., L. Wells, B.B. Quimby, and J.L. Fridovich-Keil. 1996. Heterodimer formation and activity in the human enzyme galactose-1-phosphate uridylyltransferase. Proc. Natl. Acad. Sci. USA 93: 7166-7171.

Wells, L. and J.L. Fridovich-Keil. 1996. The yeast, Saccharomyces cerevisiae, as a model system for the study of human genetic disease. SAAS Bulletin Biochem. Biotech. 9: 83-88.

Reed, R.C., V. Louis-Wileman, R.L. Wells, A.F.M. Verheul, R.L. Hunter, and A.A. Lal. 1996. Reinvestigation of the Circumsporozoite protein-based induction of sterile immunity against Plasmodium berghei infection. Vaccine 14: 828-836.

Quimby, B.B., L. Wells, K.D. Wilkinson, and J.L. Fridovich-Keil. 1996. Functional requirements of the active site position 185 in the human enzyme galactose-1-phosphate uridylyltransferase. J. Biol. Chem. 271: 26835-26842.

Wells, L. and J.L. Fridovich-Keil. 1997. Characterization of the S135L allele of human galactose-1-phosphate uridylyltransferase. J. Inh. Met. Dis. 20: 633-642.

Crews, C., K.D. Wilkinson, L. Wells, C. Perkins, and J.L. Fridovich-Keil. 2000. Functional consequences of substitutions at residue 171 in human galactose-1-phosphate uridylyltransferase. J. Biol. Chem. 275: 22847-22853.

Henderson, J.M., L. Wells, and J.L. Fridovich-Keil. 2000. Covalent heterogeneity of the human enzyme galactose-1-phosphate uridylyltransferase. J. Biol. Chem. 275: 30088-30091.

Christacos, N.C., M.J. Marson, L. Wells, K. Riehman, and J.L. Fridovich-Keil. 2000. Subcellular localization of galactose-1-phosphate uridylyltransferase in the yeast Saccharomyces cerevisiae. Mol. Genet. Metab. 70: 272-280.

Gao, Y., L. Wells, F.I. Comer, G.J. Parker, and G.W. Hart. 2001. Dynamic O-glycosylation of nuclear and cytosolic proteins: Cloning and characterization of a neutral, cytosolic b-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276: 9838-9845.

Wells, L., K. Vosseller, and G.W. Hart. 2001. Glycosylation of nucleocytoplasmic proteins: Signal transduction and O-GlcNAc. Science 291: 2376-2378.

Comer, F.I., K. Vosseller, L. Wells, and G.W. Hart. 2001. Characterization of a mouse monoclonal antibody specific for O-GlcNAc. Anal. Biochem. 293: 169-177.

Vosseller, K., L. Wells, and G.W. Hart. 2001. Nucleo-cytoplasmic glycosylation: Proteomics and O-GlcNAc. Biochimie 83: 575-581.

Wells, L., Y. Gao, J. Mahoney, K. Vosseller, C. Chen, A. Rosen, and G.W. Hart. 2001. Dynamic O-glycosylation of nuclear and cytosolic proteins: Further characterization of the nucleocytoplasmic b-N-acetylglucosaminidase, O-GlcNAcase. J. Biol. Chem. 277: 1755-1761.

Vosseller, K., L. Wells, M.D. Lane, and 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 99: 5313-5318.

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

Wells, L., K. Vosseller, and G.W. Hart. 2003. A role for O-GlcNAc as a nutrient sensor and mediator of insulin resistance. Cell. Mol. Life Sci. 60: 222-228.

Vosseller, K., K. Sakabe, L. Wells, and G.W. Hart. 2003. Diverse regulation of protein function by O-GlcNAc, a nuclear and cytoplasmic carbohydrate post-translational modification. Curr. Opin. Chem. Biol. 6: 851-857.

Wells, L., S.A. Whalen, and G.W. Hart. 2003. O-GlcNAc: A regulatory post-translational modification. Biochem. Biophys. Res. Comm. 302: 435-441.

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

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

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

Vosseller, K., K.C. Hansen, R.J. Chalkley, J.C. Trinidad, L. Wells, G.W. Hart, and 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.

Akimoto, Y., K. Yamamoto, E. Munetomo, L. Wells, K. Vosseller, G.W. Hart, H. Kawakami, and 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.

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

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

Woosley, B.D., V.S. Kumar-Kolli, L. Wells, D. King, R. Poe, R. Orlando, and C. Bergmann. 2006. Glycan analysis of recombinant Aspergillus niger endo-polygalacturonase A. Carbohydr Res. In press.