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Assistant Professor of Biochemistry and Biophysics
in the Center for Oral Biology
Ph.D. University of Calgary 1990

We study glycosylation because multi-cellular organisms have evolved hundreds of gene products that are involved in post-translational modification of the cell surface. Cell surface molecules mediate cell-cell interactions, signaling events and structures that are important for development of tissues and organs. Defects in the post-translational modification machinery result in severe inherited disorders. The most prevalent class of cell-surface molecules are glycoconjugates, which are proteins, lipids or carbohydrates that are modified with sugar chains (oligosaccharides). In mass terms, the saccharide component of a glycoprotein can account for up to 85% of its molecular weight. In terms of complexity, literally millions of different complex carbohydrate side chains can be synthesized, and these are expressed in tissue-specific patterns throughout development.

The role of carbohydrate chain modification in development, however, has not been closely examined for hundreds of glycosyltransferase genes. For this reason the study of glycosylation in development is in its infancy. We hypothesize that many different classes of oligosaccharides on the cell surface are crucial for orchestrating development processes because many unique glycoconjugate structures are expressed in specific temporal and spatial patterns throughout development.

A Comprehensive Functional Genomics Screen of Glycosyltransferases. Our objective is to identify every member of the glycosyltransferase superfamily, using motif modeling and searching strategies. Each of these glycosyltransferases will be cloned and targeted in a reverse genetic screen to identify those glycosyltransferases that are critical for development. We believe that C. elegans is best suited for a comprehensive genomics approach because it is a very simple organism, composed of about 1000 somatic cells, in which the complete cell lineage is known at single cell resolution. Furthermore, C. elegans is amenable to genetic manipulation and rapid RNA interference screens. These features will allow us to screen each glycosyltransferase gene for a loss-of-function phenotype. Those glycosyltransferases that are critical of development will then be characterized biochemically and structurally so that we can work on the interface of biology and biochemistry to elucidate important novel mechanisms in development.

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Recent Publications

Tenno M, Ohtsubo K, Hagen FK, Ditto D, Zarbock A, Schaerli P, von Andrian UH, Ley K, Le D, Tabak LA, Marth JD (2007) Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity. Mol Cell Biol, 27:8783-96

Wang H, Julenius K, Hryhorenko J, Hagen FK (2007) Systematic Analysis of proteoglycan modification sites in Caenorhabditis elegans by scanning mutagenesis. J Biol Chem, 282:14586-97

Wang H, Spang A, Sullivan MA, Hryhorenko J, Hagen FK (2005) The terminal phase of cytokinesis in the Caenorhabditis elegans early embryo requires protein glycosylation. Mol Biol Cell, 16:4202-13

Wojczyk BS, Stwora-Wojczyk MM, Hagen FK, Striepen B, Hang HC, Bertozzi CR, Roos DS, Spitalnik SL (2003) cDNA cloning and expression of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase T1 from Toxoplasma gondii. Mol Biochem Parasitol, 131:93-107

Hagen FK, Ten Hagen KG, Tabak LA (2002) UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. In: Handbook of Glycosyltransferases and Their Related Genes. (N Taniguchi and M. Fukuda, Ed.), Springer-Verlag, Tokyo,

Ten Hagen KG, Bedi GS, Tetaert D, Kingsley PD, Hagen FK, Balys MM, Beres TM, Degand P, Tabak LA (2001) Cloning and characterization of a ninth member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9. J Biol Chem, 276:17395-404

Hagen FK, Layden M, Nehrke K, Gentile K, Berbach K, Tsao CC, Forsythe M (2001) Mucin-type O-Glycosylation in C. elegans is initiated by a family of glycosyltransferases. TIGG , 13:463-479

Ten Hagen KG, Tetaert D, Hagen FK, Richet C, Beres TM, Gagnon J, Balys MM, VanWuyckhuyse B, Bedi GS, Degand P, Tabak LA (1999) Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity. J Biol Chem, 274:27867-74

Hagen FK, Hazes B, Raffo R, deSa D, Tabak LA (1999) Structure-function analysis of the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Essential residues lie in a predicted active site cleft resembling a lactose repressor fold. J Biol Chem, 274:6797-803

Ten Hagen KG, Hagen FK, Balys MM, Beres TM, Van Wuyckhuyse B, Tabak LA (1998) Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem, 273:27749-54

Hagen FK, Nehrke K (1998) cDNA cloning and expression of a family of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans. J Biol Chem, 273:8268-77

Nehrke K, Hagen FK, Tabak LA (1998) Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo. Glycobiology, 8:367-71

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Genetics

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: Fred_Hagen@urmc.rochester.edu

Fred Hagen
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 611
Rochester, New York 14642

Office: Medical Center KMRB G-9631
Telephone: (585) 275-0336; Fax: (585) 473-2679