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Fred Hagen

TitleResearch Assistant Prof (Part-Time)
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester NY 14642
 
 Awards And Honors
1980     President's Undergraduate Fellowship, University of California, Davis Independent Study
1981     California Foundation for Biochemical Research Fellowship, University of California, Davis
1981 - 1983DAAD (German Academic Exchange), Max Planck Institut, W. Germany
1983     NATO Travel Grant/Faculty of Medicine Summer Studentship, U. Calgary, Alberta, Canada
1983     Max Planck Fellowship, Max Planck Institut, W. Germany
1984 - 1988Alberta Heritage Foundation for Medical Research Studentship, U. Calgary, Alberta, Canada
1985 - 1987Tuition Fee Scholarship, U. Calgary, Alberta, Canada, Graduate Studies
1989     Graduate Assistantship (TRUST), Faculty of Medicine Trust Fund, U. Calgary, Alberta, Canada
1991 - 1992NIDR: Oral Cellular and Molecular Biology Research Training Grant, University of Rochester
1998     University of Rochester Nominee to Searle Scholars Program
 
 Overview
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.

 
 Selected Publications
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  1. Nadtochiy SM, Madukwe J, Hagen F, Brookes PS. Mitochondrially targeted nitro-linoleate: a new tool for the study of cardioprotection. Br J Pharmacol. 2014 Apr; 171(8):2091-8.
    View in: PubMed
  2. Pei S, Minhajuddin M, Callahan KP, Balys M, Ashton JM, Neering SJ, Lagadinou ED, Corbett C, Ye H, Liesveld JL, O'Dwyer KM, Li Z, Shi L, Greninger P, Settleman J, Benes C, Hagen FK, Munger J, Crooks PA, Becker MW, Jordan CT. Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells. J Biol Chem. 2013 Nov 22; 288(47):33542-58.
    View in: PubMed
  3. Lu XL, Najafzadeh MJ, Dolatabadi S, Ran YP, Gerrits van den Ende AH, Shen YN, Li CY, Xi LY, Hao F, Zhang QQ, Li RY, Hu ZM, Lu GX, Wang JJ, Drogari-Apiranthitou M, Klaassen C, Meis JF, Hagen F, Liu WD, de Hoog GS. Taxonomy and epidemiology of Mucor irregularis, agent of chronic cutaneous mucormycosis. Persoonia. 2013 Jun; 30:48-56.
    View in: PubMed
  4. Miralem T, Lerner-Marmarosh N, Gibbs PE, Tudor C, Hagen FK, Maines MD. The human biliverdin reductase-based peptide fragments and biliverdin regulate protein kinase Cd activity: the peptides are inhibitors or substrate for the protein kinase C. J Biol Chem. 2012 Jul 13; 287(29):24698-712.
    View in: PubMed
  5. Hagen FK. Proteoglycan: site mapping and site-directed mutagenesis. Methods Mol Biol. 2012; 836:23-34.
    View in: PubMed
  6. Wangler NJ, Santos KL, Schadock I, Hagen FK, Escher E, Bader M, Speth RC, Karamyan VT. Identification of membrane-bound variant of metalloendopeptidase neurolysin (EC 3.4.24.16) as the non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site. J Biol Chem. 2012 Jan 2; 287(1):114-22.
    View in: PubMed
  7. Griffiths AE, Wang W, Hagen FK, Fay PJ. Use of affinity-directed liquid chromatography-mass spectrometry to map the epitopes of a factor VIII inhibitor antibody fraction. J Thromb Haemost. 2011 Aug; 9(8):1534-40.
    View in: PubMed
  8. Marimuthu S, Chivukula RS, Alfonso LF, Moridani M, Hagen FK, Bhat GJ. Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets. Int J Oncol. 2011 Nov; 39(5):1273-83.
    View in: PubMed
  9. Nasim S, Pei S, Hagen FK, Jordan CT, Crooks PA. Melampomagnolide B: a new antileukemic sesquiterpene. Bioorg Med Chem. 2011 Feb 15; 19(4):1515-9.
    View in: PubMed
  10. Ambatipudi KS, Hagen FK, Delahunty CM, Han X, Shafi R, Hryhorenko J, Gregoire S, Marquis RE, Melvin JE, Koo H, Yates JR. Human common salivary protein 1 (CSP-1) promotes binding of Streptococcus mutans to experimental salivary pellicle and glucans formed on hydroxyapatite surface. J Proteome Res. 2010 Dec 3; 9(12):6605-14.
    View in: PubMed
  11. Ambatipudi KS, Lu B, Hagen FK, Melvin JE, Yates JR. Quantitative analysis of age specific variation in the abundance of human female parotid salivary proteins. J Proteome Res. 2009 Nov; 8(11):5093-102.
    View in: PubMed
  12. Gonzalez-Begne M, Lu B, Han X, Hagen FK, Hand AR, Melvin JE, Yates JR. Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). J Proteome Res. 2009 Mar; 8(3):1304-14.
    View in: PubMed
  13. Denny P, Hagen FK, Hardt M, Liao L, Yan W, Arellanno M, Bassilian S, Bedi GS, Boontheung P, Cociorva D, Delahunty CM, Denny T, Dunsmore J, Faull KF, Gilligan J, Gonzalez-Begne M, Halgand F, Hall SC, Han X, Henson B, Hewel J, Hu S, Jeffrey S, Jiang J, Loo JA, Ogorzalek Loo RR, Malamud D, Melvin JE, Miroshnychenko O, Navazesh M, Niles R, Park SK, Prakobphol A, Ramachandran P, Richert M, Robinson S, Sondej M, Souda P, Sullivan MA, Takashima J, Than S, Wang J, Whitelegge JP, Witkowska HE, Wolinsky L, Xie Y, Xu T, Yu W, Ytterberg J, Wong DT, Yates JR, Fisher SJ. The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions. J Proteome Res. 2008 May; 7(5):1994-2006.
    View in: PubMed
  14. Tenno M, Ohtsubo K, Hagen FK, Ditto D, Zarbock A, Schaerli P, von Andrian UH, Ley K, Le D, Tabak LA, Marth JD. Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity. Mol Cell Biol. 2007 Dec; 27(24):8783-96.
    View in: PubMed
  15. Wang H, Julenius K, Hryhorenko J, Hagen FK. Systematic Analysis of proteoglycan modification sites in Caenorhabditis elegans by scanning mutagenesis. J Biol Chem. 2007 May 11; 282(19):14586-97.
    View in: PubMed
  16. Wang H, Spang A, Sullivan MA, Hryhorenko J, Hagen FK. The terminal phase of cytokinesis in the Caenorhabditis elegans early embryo requires protein glycosylation. Mol Biol Cell. 2005 Sep; 16(9):4202-13.
    View in: PubMed
  17. Wojczyk BS, Stwora-Wojczyk MM, Hagen FK, Striepen B, Hang HC, Bertozzi CR, Roos DS, Spitalnik SL. cDNA cloning and expression of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase T1 from Toxoplasma gondii. Mol Biochem Parasitol. 2003 Oct; 131(2):93-107.
    View in: PubMed
  18. Ten Hagen KG, Bedi GS, Tetaert D, Kingsley PD, Hagen FK, Balys MM, Beres TM, Degand P, Tabak LA. Cloning and characterization of a ninth member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9. J Biol Chem. 2001 May 18; 276(20):17395-404.
    View in: PubMed
  19. Ten Hagen KG, Tetaert D, Hagen FK, Richet C, Beres TM, Gagnon J, Balys MM, VanWuyckhuyse B, Bedi GS, Degand P, Tabak LA. Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity. J Biol Chem. 1999 Sep 24; 274(39):27867-74.
    View in: PubMed
  20. Hagen FK, Hazes B, Raffo R, deSa D, Tabak LA. 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. 1999 Mar 5; 274(10):6797-803.
    View in: PubMed
  21. Ten Hagen KG, Hagen FK, Balys MM, Beres TM, Van Wuyckhuyse B, Tabak LA. Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem. 1998 Oct 16; 273(42):27749-54.
    View in: PubMed
  22. Hagen FK, Nehrke K. cDNA cloning and expression of a family of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans. J Biol Chem. 1998 Apr 3; 273(14):8268-77.
    View in: PubMed
  23. Nehrke K, Hagen FK, Tabak LA. Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo. Glycobiology. 1998 Apr; 8(4):367-71.
    View in: PubMed
  24. Nehrke K, Ten Hagen KG, Hagen FK, Tabak LA. Charge distribution of flanking amino acids inhibits O-glycosylation of several single-site acceptors in vivo. Glycobiology. 1997 Dec; 7(8):1053-60.
    View in: PubMed
  25. Wragg S, Hagen FK, Tabak LA. Identification of essential histidine residues in UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T1. Biochem J. 1997 Nov 15; 328 ( Pt 1):193-7.
    View in: PubMed
  26. Hagen FK, Ten Hagen KG, Beres TM, Balys MM, VanWuyckhuyse BC, Tabak LA. cDNA cloning and expression of a novel UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. J Biol Chem. 1997 May 23; 272(21):13843-8.
    View in: PubMed
  27. Zara J, Hagen FK, Ten Hagen KG, Van Wuyckhuyse BC, Tabak LA. Cloning and expression of mouse UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3. Biochem Biophys Res Commun. 1996 Nov 1; 228(1):38-44.
    View in: PubMed
  28. Albone EF, Hagen FK, Szpirer C, Tabak LA. Molecular cloning and characterization of the gene encoding rat submandibular gland apomucin, Mucsmg. Glycoconj J. 1996 Oct; 13(5):709-16.
    View in: PubMed
  29. Brockhausen I, Toki D, Brockhausen J, Peters S, Bielfeldt T, Kleen A, Paulsen H, Meldal M, Hagen F, Tabak LA. Specificity of O-glycosylation by bovine colostrum UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase using synthetic glycopeptide substrates. Glycoconj J. 1996 Oct; 13(5):849-56.
    View in: PubMed
  30. Nehrke K, Hagen FK, Tabak LA. Charge distribution of flanking amino acids influences O-glycan acquisition in vivo. J Biol Chem. 1996 Mar 22; 271(12):7061-5.
    View in: PubMed
  31. Hennet T, Hagen FK, Tabak LA, Marth JD. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc Natl Acad Sci U S A. 1995 Dec 19; 92(26):12070-4.
    View in: PubMed
  32. Hagen FK, Gregoire CA, Tabak LA. Cloning and sequence homology of a rat UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. Glycoconj J. 1995 Dec; 12(6):901-9.
    View in: PubMed
  33. Wragg S, Hagen FK, Tabak LA. Kinetic analysis of a recombinant UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase. J Biol Chem. 1995 Jul 14; 270(28):16947-54.
    View in: PubMed
  34. Albone EF, Hagen FK, VanWuyckhuyse BC, Tabak LA. Molecular cloning of a rat submandibular gland apomucin. J Biol Chem. 1994 Jun 17; 269(24):16845-52.
    View in: PubMed
  35. Hagen FK, Van Wuyckhuyse B, Tabak LA. Purification, cloning, and expression of a bovine UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferase. J Biol Chem. 1993 Sep 5; 268(25):18960-5.
    View in: PubMed
  36. O'Connell BC, Hagen FK, Tabak LA. The influence of flanking sequence on the O-glycosylation of threonine in vitro. J Biol Chem. 1992 Dec 15; 267(35):25010-8.
    View in: PubMed
  37. Aiken JM, Miller FD, Hagen F, McKenzie DI, Krawetz SA, van de Sande JH, Rattner JB, Dixon GH. Tandem repeats of a specific alternating purine-pyrimidine DNA sequence adjacent to protamine genes in the rainbow trout that can exist in the Z form. Biochemistry. 1985 Oct 22; 24(22):6268-76.
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  38. Hagen FK, Zarling DA, Jovin TM. Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG. EMBO J. 1985 Mar; 4(3):837-44.
    View in: PubMed

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