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Fred Hagen, Ph.D.

Contact Information

Phone Numbers

Fax: (585) 276-0190

Office: (585) 275-0336

Research Labs

Biography

Research

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.

Credentials

Faculty Appointments

Education

1989
PhD | Canada-U Calgary Fac Med
Biochemistry

1981
BS | Univ of Cal Davis
Biochemistry

Awards

1998
University of Rochester Nominee to Searle Scholars Program

1991 - 1992
NIDR: Oral Cellular and Molecular Biology Research Training Grant, University of Rochester

1989
Graduate Assistantship (TRUST), Faculty of Medicine Trust Fund, U. Calgary, Alberta, Canada

1985 - 1987
Tuition Fee Scholarship, U. Calgary, Alberta, Canada, Graduate Studies

1984 - 1988
Alberta Heritage Foundation for Medical Research Studentship, U. Calgary, Alberta, Canada

1983
NATO Travel Grant/Faculty of Medicine Summer Studentship, U. Calgary, Alberta, Canada

1983
Max Planck Fellowship, Max Planck Institut, W. Germany

1981 - 1983
DAAD (German Academic Exchange), Max Planck Institut, W. Germany

1981
California Foundation for Biochemical Research Fellowship, University of California, Davis

1980
President's Undergraduate Fellowship, University of California, Davis Independent Study

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Publications

Journal Articles

10/2014
De C, Liu D, Zheng B, Singh US, Chavre S, White C, Arnold RD, Hagen FK, Chu CK, Moffat JF. "?-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (l-BHDU) prevents varicella-zoster virus replication in a SCID-Hu mouse model and does not interfere with 5-fluorouracil catabolism." Antiviral research.. 2014 Oct 0; 110:10-9. Epub 2014 Jul 19.

9/15/2014
Tian L, Wang C, Hagen FK, Gormley M, Addya S, Soccio R, Casimiro MC, Zhou J, Powell MJ, Xu P, Deng H, Sauve AA, Pestell RG. "Acetylation-defective mutant of Ppar? is associated with decreased lipid synthesis in breast cancer cells." Oncotarget. 2014 Sep 15; 5(17):7303-15.

8/2014
Beckham CJ, Olsen J, Yin PN, Wu CH, Ting HJ, Hagen FK, Scosyrev E, Messing EM, Lee YF. "Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression." The Journal of urology.. 2014 Aug 0; 192(2):583-92. Epub 2014 Feb 14.

Books & Chapters

2003
Chapter Title: UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases.
Book Title: Handbook of Glycosyltransferases and Their Related Genes
Author List: Hagen, F.K.; Ten Hagen, K.G.; Tabak ,L.A.
Edited By: N. Taniguchi and M. Fukuda
Published By: Springer-Verlag2003 in Tokyo

1996
Chapter Title: Experimental approaches to studying O-glycosylation in vivo.
Book Title: Techniques in Glycobiology
Author List: Nehrke, K.N.; Hagen, F.K.; Tabak, L.A .
Edited By: R.R. Townsend
Published By: Marcel Dekker, Inc.1996 in New York

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