Brett D. Keiper, PhD
Professor & Graduate Program Director
Graduate Council Executive Committee
Brody 5S-26
The Brody School of Medicine at East Carolina University
Greenville, NC 27834
phone: 252-744-2656
email: keiperb@ecu.edu
Education
- Philipps Universitaet Marburg, Germany, 1983-1984
- B.Sc., Juniata College, 1985
- PhD., Brandeis University, 1991
- Postdoctorate, Boehringer-Ingelheim Pharmaceuticals, Vienna, Austria
- Postdoctorate, LSU Health Sciences Center
- Research Assistant Professor, LSU Health Sciences Center
Research Interests
- mRNA regulation in germ cells, embryos and tumors
- Cell differentiation, proliferation and apoptosis
We recognize that new proteins often lead to a new cell fate. The mechanisms that select mRNAs for translation on ribosomes change the protein composition of a cell, pushing it forward in development. Our research suggests that mRNA control is selectively and elegantly regulated by the translation initiation factors themselves, particularly in germ cells (that produce gametes, sperm and oocytes) and in early embryos. But our findings may be just as important for RNA virus functions and cancer progression. Our research methods include biochemical methods, microinjection, genetics and bioinformatics to study mRNA in the nematode, C. elegans. The worms reproduce rapidly, are transparent (making microscopy ideal) and are easily gene edited using CrispR/Cas9. Our focus is on how mRNAs are selected during growth, differentiation or even cell death (apoptosis) phases of development. The mechanisms are a novel point of intervention against RNA viruses, birth defects and certain cancers.
Selected Publications
Rochester JD, Min H, Gajjar GA, Sharp CS, Maki NJ, Rollins JA, Keiper BD, Graber JH, Updike DL. (2022) GLH-1/Vasa represses neuropeptide expression and drives spermiogenesis in the C. elegans germline. Dev Biol. 492:200-211. doi: 10.1016/j.ydbio.2022.10.003.
Huggins HP, Subash JS, Stoffel H, Henderson MA, Hoffman JL, Buckner DS, Sengupta MS, Boag PR, Lee MH, Keiper B.D. (2020) Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans. J Cell Sci. 133(6):jcs237990.
Flamand, M.N., Wu, E., Vashisht, A., Jannot, G., Keiper, B.D., Simard, M.J., Wohlschlegel, J., and Duchaine, T.F. (2016). Poly(A)-binding proteins are required for microRNA-mediated silencing and to promote target deadenylation in C. elegans. Nucleic Acids Res 44(12), 5924-5935.
Friday, A.J, Henderson, M.A., Morrison, J.K., Hoffman, J.L. and Keiper, B.D. (2015) Spatial and Temporal Translational Control of Germ Cell mRNAs mediated by the eIF4E Isoform, IFE-1. J. Cell Sci.128(24): 4487-4498.
Morrison, J.K., Friday, A, Henderson, M.A.,Hao, E., and Keiper, B.D. (2014). Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation during germ cell apoptosis. Translation (Taylor Francis) 2(1): e28,935.
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.
View complete bibliography (NCBI) listing for Dr Keiper
Invited Reviews
Huggins HP, Keiper B.D. (2020) Regulation of Germ Cell mRNPs by eIF4E:4EIP Complexes: Multiple Mechanisms, One Goal. Front Cell Dev Biol. Jul 7; 8:562. doi: 10.3389/fcell.2020.00562.
Keiper B.D. (2019) Cap-Independent mRNA Translation in Germ Cells. Int J Mol Sci. 20(1):173
Friday, A.J, and Keiper, B.D. (2015) Positive mRNA translational control in germ cells by initiation factor selectivity. Biomed Res Int. Volume 2015:327963.
Keiper, B.D. (2003) Translation of mRNAs in Xenopus Oocytes. In: Encyclopedia of Life Sciences. London: Nature Publishing Group. Online journal, February 2003.
Recent Funding
National Science Foundation
MCB-2119959, 2021-2025 Mid-Career Award
Title: “MCA: Post-nuclear granules traffic mRNAs through helicases and initiation factors to set their translational fates.”
Visiting Scientist Fellowship at Mount Desert Island Biological Labs
SCRF 2021-2023, with Dr Dustin Updike (co-PI, MDIBL, Bar Harbor, ME)
Title: “Selective control of mRNA translation by eIF4Es, eIF4G, and Vasa during germ cell development.”
National Science Foundation
MCB-1714264, 2022-2025 co-PI with Dr Myon Hee Lee (PI, ECU Dept Medicine)
Title: “Regulatory mechanism for cellular dedifferentiation in C. elegans germline.”
National Science Foundation
MCB-0842475,, 2017-2021
Title: “mRNA selection by eIF4Eisoforms and their sequestering factors”
National Science Foundation
MCB0842475, 2009-2014
Title: “Translational control of growth & apoptosis in C. elegans development by initiation factors”
National Science Foundation
MCB-0321017, 2004-2009
Title: “Function of Tissue-specific eIF4E Isoforms in Caenorhabditis elegans”