Brett Keiper | Faculty | Biochemistry and Molecular Biology | East Carolina University

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Department of Biochemistry and Molecular Biology

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Brett Keiper

Brett D. Keiper

Associate Professor Biochemistry & Molecular Biology
  • B.Sc., Juniata College, 1985
  • Ph.D., Brandeis Univ., 1991
  • Postdoctorate, Boehringer-Ingelheim Pharmaceuticals, Vienna, Austria
  • Postdoctorate, LSU Health Sciences Center
  • Research Assistant Professor, LSU Health Sciences Center

Keiper's Lab Website >

Research Interests

mRNA Translational Control in Embryos and Tumors

The regulation of protein synthesis ultimately determines most cell fate decisions. Cells undergoing any form of differentiation control both the rate of global synthesis and the types of new proteins made. The role of mRNA translational control is becoming increasingly apparent in gametogenesis, embryogenesis and oncogenesis. Intriguingly, early embryonic development displays many functional parallels to oncogenesis, among them are mRNA translational control and cell proliferation. Like a cleaving embryo, cancer cells upregulate protein synthesis and cell cycle progression relative to normal somatic cells. The focus of our studies is the protein synthesis apparatus itself (i.e. translation initiation factors), which controls the utilization of mRNAs in cells undergoing rapid growth, differentiation or even cell death (apoptosis). Translation initiation factors 4E and 4G (eIF4E and eIF4G) alter the mode of translation initiation in a way that discriminates for or against particular mRNAs. Disruption of this complex causes preferential translation of mRNAs that promote apoptosis. Protein synthesis mechanism therefore represents a novel point of intervention for cancer therapies and developmental defects. Using biochemical methods, microinjection, transgenesis, genetics and genomics in the model organism, C. elegans, we are attempting to artificially modulate eIF4E and eIF4G isoforms in vivo as a means to inhibit cell proliferation or alter differentiation pathways.

Selected Publications

Song A., Labella S., Korneeva N.L., Keiper B.D., Aamodt E.J., Zetka M. and Rhoads R.E. (2010) A C.elegans eIF4E-family member upregulates translational at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins. J. Cell Sci. 123(Pt 13): 2228-2237. (link to article)

Henderson, M.A., Cronland, E., Dunkelbarger, S., Contreras, V., Strome, S., and Keiper, B.D. (2009) A germ line-specific isoform of eIF4E (IFE-1) is required for efficient translation of stored mRNAs and maturation of both oocytes and sperm. J. Cell Sci. 122: 1529-1539. (link to article)

Contreras, V., Richardson, M.A., Hao, E. and Keiper, B.D. (2008). Depletion of the cap-associated isoform of translation factor eIF4G induces germline apoptosis in C. elegans. Cell Death Differ. 15: 1232-1242. (link to abstract)

Dinkova, T.D., Keiper, B.D., Korneeva, N.L., Aamodt, E.J. and Rhoads, R.E. (2005) Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform. Mol. Cell. Biol. 25(1): 100-113.

Miyoshi, H., Dwyer, D., Keiper, B.D., Jankowska, M., Darzynkiewicz, E. and R.E. Rhoads (2002) Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E. EMBO J. 21(17): 4680-4690.

Amiri, A., Keiper, B.D., Kawasaki, I., Fan, Y., Kohara, Y., Rhoads, R.E., and S. Strome (2001) An Isoform of eIF4E is a Component of Germ Granules and is Required for Spermatogenesis in C. elegans. Development 128 (20): 3899-3912.

Keiper, B.D., Lamphear, B.J., Deshpande, A.M., Jankowska-Anyszka, M., Aamodt, E.J., Blumenthal, T., and R.E. Rhoads (2000) Functional Characterization of Five eIF4E Isoforms in Caenorhabditis elegans. J. Biol. Chem. 275 (14): 10590-10596. (link to article)

Keiper, B.D. and R.E. Rhoads (1999b) Translational Recruitment of Xenopus Maternal mRNAs in Response to Poly(A) Elongation Requires Initiation Factor eIF4G-1. Dev. Biol. 206 (1): 1-14.

Keiper, B.D. and R.E. Rhoads (1997) Cap-Independent Translation Initiation in Xenopus Oocytes, Nucleic Acids Res. 25 (2): 395-403.

Spevak, W., Keiper, B.D., Stratowa, C., and M.J. Castanon (1993) Saccharomyces cerevisiae cdc15 Mutants Arrested at a Late Stage in Anaphase are Rescued by Xenopus cDNAs Encoding N-ras or a Protein with ß-Transducin Repeats (ßTrCP). Mol. Cell. Biol. 13 (8), 4953-4966.

Invited Reviews

Keiper, B.D. (2003) Translation of mRNAs in Xenopus Oocytes. In: Encyclopedia of Life Sciences. (Online Reviews) London: Nature Publishing Group. (http://www.els.net/)

Keiper, B.D., Gan, W., and R.E. Rhoads (1999a) Molecules in Focus: Protein Synthesis Initiation Factor 4G, Int. J. Biochem. Cell Biol. 31(1): 37-41. (link to article)

Recent Funding

National Science Foundation

NSF MCB0842475 2009-2012

Title: “Translational control of growth & apoptosis in C. elegans development by initiation factors”
National Science Foundation

NSF MCB0321017 2004-2008

Title: “Function of Tissue-specific eIF4E Isoforms in Caenorhabditis elegans”
ECU Division of Research & Graduate Studies

Research Development Grant (ECU) 2008-2009

Title: “Translational control of growth and apoptosis in the C. elegans ovary”
Leo Jenkins Cancer Center (Dr. Mary A Farwell, co-PI)

Seed Grant (ECU) 2006

Title: “Targeted depletion of N-terminally extended eIF4G-1 isoforms in breast cancer cell lines to reduce proliferation and/or increase susceptibility to apoptosis”
North Carolina Biotechnology Center (Dr. Jim McCubrey, co-PI)

2004-IDG 1002, Institutional Development Grant 2005-2006

Title: “Phosphor-Imaging and Fluorescence-Imaging Core Facility at ECU Brody School of Medicine”

Contact Information

Associate Professor of Biochemistry & Molecular Biology
Graduate Program Committee Chairman
Brody 5S-26
The Brody School of Medicine at East Carolina University
Greenville, NC 27834
phone: 252.744.2656
email: keiperb@ecu.edu

Please use our website to learn more about our program. Feel free to contact Dr. Phillip Pekala or Dr. Brett Keiper, Associate Professor and Graduate Program Committee Chairman to see if you have what it takes to shape the future in a positive manner.

TOMORROW STARTS HERE

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