Biochemistry Faculty

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

mRNA Translational Control in Embryos and Tumors

Control of mRNA translation in cell differentiation
Protein synthesis factors and isoform complexes
Rapid cell proliferation and cell cycle proteins

Selected Publications

Keiper's Lab Website

Contact Information

Faculty Page

mRNA Translational Control in Embryos and Tumors

The critical question in embryonic development is, “How do undifferentiated cells change in character to become the very specialized cells that make up the vital organs of a fetus?” The production of new and unique proteins in the few cells that make up an early embryo causes each cell to take on the character of their intended adult tissue type. Processes that introduce (synthesize) new proteins ultimately direct these cells to form distinct organ systems such as brain, muscle, gonad and gut. Cell-specific protein synthesis regulation is part of the internal genetic program that takes embryos from a uniform mass of cells to a complex adult organism. Regulation of new protein synthesis in embryos and in transformed cells is the focus of this research.

Primary tumors arise through a series of oncogenic transformation steps in normal cells that give rise to dramatic changes in cell cycle and metabolism. Cell proliferation and tumor growth is fueled, in part, by a large increase in protein synthesis. Translation initiation factors eIF4E and eIF4G recruit mRNAs for protein synthesis and have been shown to be overexpressed in breast cancers, head and neck cancers, and squamous cell lung carcinomas, among others. Ironically, cancer cell growth closely parallels early embryonic cell growth, both in the protein synthetic activity and the types of cell cycle mRNAs that are recruited. eIF4E and eIF4G activity is also high during proliferation of the germline and in rapidly dividing embryos where they similarly promote cell cycle and cell growth. We are taking advantage of the genetic and molecular tools (RNA intereference, gene knockout strains, microinjection transgenesis) available to disrupt translation initiation factor function in C. elegans and observe the consequences to proliferating germ and embryonic cells in vivo. We hope to learn what roles eIF4E and eIF4G play in the rapid growth that characterizes these tissues as a versatile animal model for the similar growth of tumors in mammals. (top)

Selected Publications

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.

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.

Kerekatte, V., Keiper, B.D., Badorff, C., Cai, A.L., Knowlton, K. and R.E. Rhoads (1999c) Cleavage of Poly(A)-Binding Protein by Coxsackieviral 2A Protease in Vitro and in Vivo: Another Mechanism for Host Protein Synthesis Shut-off? J. Virol. 73 (1): 709-717.

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.

(top)

Contact Information

Professor of Biochemistry & Molecular Biology

Brody 5S-26

The Brody School of Medicine at East Carolina University

Greenville, NC 27834

phone: 252.744.2656

email: keiperb@ecu.edu

(top)