Dr. Kelley Moremen

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University of Georgia
Complex Carbohydrate Research Center
ProfessorAppointed: 2003
Professional Headshot of Kelley Moremen

Mailing Address

Complex Carbohydrate Research Center
315 Riverbend Rd.
University of Georgia
Athens, Georgia 30602
United States

Contact Information

Phone: (706) 542-1705
Fax: (706) 542-1759
moremen@uga.edu
http://bmbiris.bmb.uga.edu/moremen/lab/

Qualifications

Ph.D., Vanderbilt University, Molecular Biology, 1984.
B.S., Dickinson College, Biology and Chemistry, 1978.

Expertise and Research Interests

My research concerns the structure, regulation, and localization of enzymes involved in the biosynthesis and catabolism of mammalian glycoproteins. Oligosaccharides have been shown to be involved in biological recognition events and influence the bioactivity of glycoconjugate structures. Alterations in the synthesis and degradation of these structures can also occur in human genetic diseases and cancer. My lab has isolated the genes encoding several of the enzymes involved in the glycoprotein biosynthesis and catabolism. In particular, research in the lab is focused on the enzymes involved in Asn-linked glycan maturation, including trimming mannosidases and glycosyltransferases, as well as lysosomal glycan catabolism in mammalian cells. The functions of these enzymes are being addressed by biochemical approaches in vitro that employ recombinant expression and purification combined with biochemical, biophysical, and structural characterization. In addition we employ expression studies in vivo to examine the roles of distinct enzymes on glycan biosynthesis and catabolism. A separate project in the lab focuses on characterizing the regulation of enzymes involved in glycan biosynthesis and catabolism. A high-throughput real-time PCR (qRT-PCR) approach has been developed in the lab for profiling the transcripts encoding all glycan related genes (gene list of >600 genes) in mouse and human cell and tissue samples. The approach is being applied for transcript analysis in cell-based models for vertebrate development and disease. Research in the lab is supported by NIH and industry.

Other Expertise

Academic Experience:
Editorial Board: Journal of Biological Chemistry (2005-present)
Glycobiology (2005-present)
Glycoconjugate Journal (1994 - present)

Business Experience:
Scientific Advisory Board, Glycofi, Inc., Hanover, NH, 2004-present
Scientific Advisory Board, Novazyme Pharmaceuticals, Inc., Oklahoma City, OK, 1999-2003
Scientific Advisory Board, Glycodesign, Inc., Toronto, Ontario, Canada 1993-1998
Consultant, Glycodesign, Inc., 1993-1997

Member, Society for Glycobiology, 1990-present
Board of Directors, 1998-2003
Secretary, 2005-present
Member, American Society for Cell Biology, 1992, present
Member, American Society for Biochemistry/Molecular Biology, 1992, present

Keywords

COS Keywords:

Biochemistry, Biosynthesis, Enzymes, Genetics, Glycobiology, Proteins and Macromolecules.

Additional Terms:

Alpha-mannosidases, Alpha-mannosidosis, Asn-linked Oligosaccharide Processing, Genetic Disease, Glycoprotein Catabolism, Glycosyltransferase, Golgi Enzymes, HEMPAS Disease, Intra-cellular Localization, Lysosomal Storage Disease, Protein Crystallography, Protein Glycosylation, Real-time PCR, Recombinant Enzyme Expression, Sialyltransferase, Surface Plasmon Resonance.

Memberships

American Society for Biochemistry and Molecular Biology
American Society for Cell Biology
Society for Glycobiology

Previous Positions

1997-2003, Associate Professor, University of Georgia, Biochemistry and Molecular Biology
1991-1997, University of Georgia, Assistant Professor
1986-1991, Massachusetts Institute of Technology, Postdoctoral Fellow
1984-1985, Vanderbilt University, Postdoctoral Fellow

Patents

Transgenic non-human mammals expressing heterologous glycosyltransferase DNA sequences produce oligosaccharides and glycoproteins in their milk, Patent Number: 6204431, 2001, Institution, United States of America.
Lectins and Coding Sequence, Patent Number: 6146849, 2000, University of Georgia, United States of America.
Oligosaccharides and glycoproteins produced in milk of transgenic non-human mammal , Patent Number: 5891698, 1999, University of Georgia, United States of America.
Transgenic non-human mammals producing oligosaccharides and glycoconjugate , Patent Number: 5892070, 1999, University of Georgia, United States of America.
Heparinase gene from flavobacterium heparanu, Patent Number: 5714376, 1998, Massachusetts Institute o, United States of America.
Transgenic non-human mammal milk comprising 2'-fucosyl-lactose, Patent Number: 5750176, 1998, University of Georgia, United States of America.
Method for obtaining a modified heparinase gene, Patent Number: 5830726, 1998, Massachusetts Institute o, United States of America.
Methods of making transgenic animals producing oligosaccharides, Patent Number: 5.700.671, 1997, University of Georgia, United States of America.

Funding Received

  • National Institutes of Health (NIH) (NCI UO1-CA91295-01): Selective mannosidase inhibitors as cancer therapeutics, May 1, 2001 to 2006.
  • National Institutes of Health (NIH) (NIGMS RO1-GM47533-14): Mannosidases In Glycoprotein Biosynthesis and Catabolism, 2005 to 2009.
  • National Institutes of Health (NIH) (NCRR P41 RR05351; P.I.: James Prestegard, Kelley W. Moremen, Senior Investigator): Research Resource for Integrated Glycotechnology, 2005 to 2010.
  • National Institutes of Health (NCRR) (P41 RR018502; P.I. Michael Pierce; Kelley Moremen, Senior Investigator): Integrated Technology Resource for Biomedical Glycomics, 2003 to 2008.

Publications

  • Karaveg K, Moremen KW (Aug 2005) Energetics of substrate binding and catalysis by class 1 (glycosylhydrolase family 47) alpha-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control., The Journal of Biological Chemistry, 280 (33), 29837-48 Abstract
  • Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW (Apr 2005) Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control., The Journal of Biological Chemistry, 280 (16), 16197-207 Abstract
  • Mast SW, Diekman K, Karaveg K, Davis A, Sifers RN, Moremen KW (Apr 2005) Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins., Glycobiology, 15 (4), 421-36 Abstract
  • Li B, Kawatkar SP, George S, Strachan H, Woods RJ, Siriwardena A, Moremen KW, Boons GJ (Sep 2004) Inhibition of Golgi mannosidase II with mannostatin A analogues: synthesis, biological evaluation, and structure-activity relationship studies., Chembiochem : a European Journal of Chemical Biology, 5 (9), 1220-7 Abstract
  • Tempel W, Karaveg K, Liu ZJ, Rose J, Wang BC, Moremen KW (Jul 2004) Structure of mouse Golgi alpha-mannosidase IA reveals the molecular basis for substrate specificity among class 1 (family 47 glycosylhydrolase) alpha1,2-mannosidases., The Journal of Biological Chemistry, 279 (28), 29774-86 Abstract
  • Lee JK, Baum LG, Moremen K, Pierce M (2004) The X-lectins: a new family with homology to the Xenopus laevis oocyte lectin XL-35., Glycoconjugate Journal, 21 (8-9), 443-50 Abstract
  • Wu Y, Swulius MT, Moremen KW, Sifers RN (Jul 2003) Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation., Proceedings of the National Academy of Sciences of the United States of America., 100 (14), 8229-34 Abstract
  • Moremen KW (Dec 2002) Golgi alpha-mannosidase II deficiency in vertebrate systems: implications for asparagine-linked oligosaccharide processing in mammals., Biochimica Et Biophysica Acta, 1573 (3), 225-35 Abstract
  • Cabral CM, Liu Y, Moremen KW, Sifers RN (Aug 2002) Organizational diversity among distinct glycoprotein endoplasmic reticulum-associated degradation programs., Molecular Biology of the Cell, 13 (8), 2639-50 Abstract
  • Akama TO, Nakagawa H, Sugihara K, Narisawa S, Ohyama C, Nishimura S, O'Brien DA, Moremen KW, Millan JL, Fukuda MN (Jan 2002) Germ cell survival through carbohydrate-mediated interaction with Sertoli cells., Science, 295 (5552), 124-7 Abstract
  • Kawar Z, Karaveg K, Moremen KW, Jarvis DL (May 2001) Insect cells encode a class II alpha-mannosidase with unique properties., The Journal of Biological Chemistry, 276 (19), 16335-40 Abstract
  • Oh-Eda M, Nakagawa H, Akama TO, Lowitz K, Misago M, Moremen KW, Fukuda MN, Overexpression of the Golgi-localized enzyme alpha-mannosidase IIx in Chinese hamster ovary cells results in the conversion of hexamannosyl-N-acetylchitobiose to tetramannosyl-N-acetylchitobiose in th, European Journal of Biochemistry, 268(5), 1280-8, March 2001 Abstract
  • Rivera-Marrero CA, Ritzenthaler JD, Roman J, Moremen KW, Molecular cloning and expression of an alpha-mannosidase gene in Mycobacterium tuberculosis, Microbial Pathogenesis, 30(1), 9-18, Jan 2001 Abstract
  • Lee JK, Schnee J, Pang M, Wolfert M, Baum LG, Moremen KW, Pierce M, Human homologs of the Xenopus oocyte cortical granule lectin XL35, Glycobiology, 11(1), 65-73, Jan 2001 Abstract
  • Vallee, F, Karaveg, K, Herscovics, A, Moremen, K.W, Howell, P.L., Structural basis for catalysis and inhibition of N-glycan processing Class 1 a1,2-mannosidases, Journal of Biological Chemistry, 275, 41287-41298, 2000
  • Gonzalez DS, Karaveg K, Vandersall-Nairn AS, Lal A, Moremen KW, Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosa, Journal of Biological Chemistry, 274(30), 21375-86, 23 Jul 1999 Abstract
  • Igdoura SA, Herscovics A, Lal A, Moremen KW, Morales CR, Hermo L, Alpha-mannosidases involved in N-glycan processing show cell specificity and distinct subcompartmentalization within the Golgi apparatus of cells in the testis and epididymis, European Journal of Cell Biology, 78(7), 441-52, July 1999 Abstract
  • Di Virgilio S, Glushka J, Moremen K, Pierce M, Enzymatic synthesis of natural and 13C enriched linear poly-N-acetyllactosamines as ligands for galectin-1, Glycobiology, 9(4), 353-64, April 1999 Abstract
  • Gonzalez DS, Kagawa Y, Moremen KW, Isolation and characterization of the gene encoding the mouse broad specificity lysosomal alpha-mannosidase1, Biochimica Et Biophysica Acta, 1445(1), 177-83, April 1999 Abstract
  • Vallee F, Lal A, Moremen KW, Howell PL, Purification, crystallization and preliminary X-ray crystallographic analysis of recombinant murine Golgi mannosidase IA, a class I alpha-mannosidase involved in Asn-linked oligosaccharide maturation, Acta Crystallographica, Section D: Biological Crystallography, 55 ( Pt 2), 571-3, February 1999 Abstract
  • Vandersall-Nairn AS, Merkle RK, O''Brien K, Oeltmann TN, Moremen KW, Cloning, expression, purification, and characterization of the acid alpha-mannosidase from Trypanosoma cruzi., Glycobiology, 8(12), 1183-94, December 1998 Abstract
  • Howard S, Braun C, McCarter J, Moremen K W, Liao Y F, Withers S G, Human lysosomal and jack bean alpha-mannosidases are retaining glycosidases., Biochemical and Biophysical Research Communications, 238(3), 896-8, 29 Sep 1997 Abstract
  • Merkle R K, Zhang Y, Ruest P J, Lal A, Liao Y F, Moremen K W, Cloning, expression, purification, and characterization of the murine lysosomal acid alpha-mannosidase., Biochimica Et Biophysica Acta, 1336(2), 132-46, 29 Aug 1997 Abstract
  • Chui D, Oh-Eda M, Liao Y F, Panneerselvam K, Lal A, Marek K W, Freeze H H, Moremen K W, Fukuda M N, Marth J D, Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis., Cell, 90(1), 157-67, 11 Jul 1997 Abstract
  • Jarvis D L, Bohlmeyer D A, Liao Y F, Lomax K K, Merkle R K, Weinkauf C, Moremen K W, Isolation and characterization of a class II alpha-mannosidase cDNA from lepidopteran insect cells., Glycobiology, 7(1), 113-27, February 1997 Abstract
  • Liao Y F, Lal A, Moremen K W, Cloning, expression, purification, and characterization of the human broad specificity lysosomal acid alpha-mannosidase., Journal of Biological Chemistry, 271(45), 28348-58, 8 Nov 1996 Abstract
  • Prieto PA, Mukerji P, Kelder B, Erney R, Gonzalez D, Yun JS, Smith DF, Moremen KW, Nardelli C, Pierce M, Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase, Journal of Biological Chemistry, 270(49), 29515-9, 1995 Abstract
  • Misago M, Liao Y F, Kudo S, Eto S, Mattei M G, Moremen K W, Fukuda M N, Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme., Proceedings of the National Academy of Sciences (USA), 92(25), 11766-70, 5 Dec 1995 Abstract
  • Moremen K W, Trimble R B, Herscovics A, Glycosidases of the asparagine-linked oligosaccharide processing pathway., Glycobiology, 4(2), 113-25, April 1994 Abstract
  • Lal A, Schutzbach J S, Forsee W T, Neame P J, Moremen K W, Isolation and expression of murine and rabbit cDNAs encoding an alpha 1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides., Journal of Biological Chemistry, 269(13), 9872-81, 1 Apr 1994 Abstract
  • Herscovics A, Schneikert J, Athanassiadis A, Moremen K W, Isolation of a mouse Golgi mannosidase cDNA, a member of a gene family conserved from yeast to mammals., Journal of Biological Chemistry, 269(13), 9864-71, 1 Apr 1994 Abstract
  • Velasco A, Hendricks L, Moremen KW, Tulsiani DR, Touster O, Farquhar MG, Cell type-dependent variations in the subcellular distribution of alpha-mannosidase I and II, Journal of Cell Biology, 122(1), 39-51, July 1993 Abstract
  • Abeijon C, Yanagisawa K, Mandon EC, Hausler A, Moremen K, Hirschberg CB, Robbins PW, Guanosine diphosphatase is required for protein and sphingolipid glycosylation in the Golgi lumen of Saccharomyces cerevisiae, Journal of Cell Biology, 122(2), 307-23, July 1993 Abstract
  • Sasisekharan R, Bulmer M, Moremen KW, Cooney CL, Langer R, Cloning and expression of heparinase I gene from Flavobacterium heparinum, Proceedings of the National Academy of Sciences (USA), 90(8), 3660-4, 1993 Abstract
  • Moremen KW, Robbins PW, Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans, Journal of Cell Biology, 115(6), 1521-34, December 1991 Abstract
  • Zuber C, Roth J, Misteli T, Nakano A, Moremen K, DS28-6, a temperature-sensitive mutant of Chinese hamster ovary cells, expresses key phenotypic changes associated with brefeldin A treatment, Proceedings of the National Academy of Sciences (USA), 88(21), 9818-22, 1991 Abstract
  • Moremen KW, Touster O, Robbins PW, Novel purification of the catalytic domain of Golgi alpha-mannosidase II. Characterization and comparison with the intact enzyme, Journal of Biological Chemistry, 266(25), 16876-85, 1991 Abstract
  • Bischoff J, Moremen K, Lodish HF, Isolation, characterization, and expression of cDNA encoding a rat liver endoplasmic reticulum alpha-mannosidase, Journal of Biological Chemistry, 265(28), 17110-7, 1990 Abstract
  • Fukuda M N, Masri K A, Dell A, Luzzatto L, Moremen K W, Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II., Proceedings of the National Academy of Sciences (USA), 87(19), 7443-7, October 1990 Abstract
  • Moremen KW, Isolation of a rat liver Golgi mannosidase II clone by mixed oligonucleotide-primed amplification of cDNA, Proceedings of the National Academy of Sciences (USA), 86(14), 5276-80, July 1989 Abstract
  • Moremen KW, Touster O, Topology of mannosidase II in rat liver Golgi membranes and release of the catalytic domain by selective proteolysis, Journal of Biological Chemistry, 261(23), 10945-51, 1986 Abstract
  • Moremen KW, Touster O, Biosynthesis and modification of Golgi mannosidase II in HeLa and 3T3 cells, Journal of Biological Chemistry, 260(11), 6654-62, 1985 Abstract
  • Jarvis, D.L., Bohlmeyer, D.A., Liao, Y.-F., Lomax, K.K., Merkle, R.K., Lal, A., and Moremen, K.W. (1997) Isolation and characterization of a class II a-mannosidase cDNA from lepidopteran insect cells, Glycobiology, 7, 113-127
  • Merkle, R.K., Zhang, Y., Ruest, P.J., Lal, A., Liao, Y.-F., and Moremen, K.W. (1997) Cloning, expression, purification, and charcterization of the murine lysosomal acid a-mannosidase. Biochim. Biophys. Acta. in press
  • Lee, J.- K., Buckhaults, P., Wilkes, C., Teilhet, M., King, M. L, Moremen, K. W., and Pierce, M. (1997) Cloning and expression of a Xenopus laevis oocyte lectin and characterization of its mRNA levels during early development. Glycobiology, in press
  • Liao, Y.-F., Lal, A., and Moremen, K.W. (1996) Cloning, expression, purification, and characterization of the human broad specificity lysosomal acid alpha-mannosidase J. Biol. Chem, 271, 28348-28358
  • Lal, A., Schutzbach, J.S., Forsee, W.T. Neame, P. and Moremen, K. (1994) Isolation and expression of a murine and rabbit alpha 1, 2-Mannosidase involved in the processing of asparagine-linked oligosaccharides. J. Biol. Chem. 269, 9872-9881

Profile Details

Last Verified: 1/20/2006

COS Expertise ID #300132
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