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Fred Hagen, Ph.D.

Contact Information

Phone Numbers

Office: (585) 275-0336

Fax: (585) 276-0190

Research Labs

Lab: (585) 275-0380

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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

1981
BS | Univ of Cal Davis
Biochemistry

1989
PhD | Canada-U Calgary Fac Med
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

11/25/2016
Pei S, Minhajuddin M, D'Alessandro A, Nemkov T, Stevens BM, Adane B, Khan N, Hagen FK, Yadav VK, De S, Ashton JM, Hansen KC, Gutman JA, Pollyea DA, Crooks PA, Smith C, Jordan CT. "Rational design of a parthenolide-based drug regimen that selectively eradicates acute myelogenous leukemia stem cells." The Journal of biological chemistry.. 2016 Nov 25; 291(48):25280.

10/14/2016
Pei S, Minhajuddin M, D'Alessandro A, Nemkov T, Stevens BM, Adane B, Khan N, Hagen FK, Yadav VK, De S, Ashton JM, Hansen KC, Gutman JA, Pollyea DA, Crooks PA, Smith C, Jordan CT. "Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells." The Journal of biological chemistry.. 2016 Oct 14; 291(42):21984-22000. Epub 2016 Aug 29.

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.

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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