Kenneth Eilertsen, Ph.D.
Epigenetics and Nuclear Reprogramming
Ph.D., Florida State University, Tallahassee, FL, 1994, Biochemistry, Molecular and Cell Biology, Program in Molecular Biophysics
M.S., Florida State University, Tallahassee, FL, 1988, Science Education - Information Technologies
B.S., Florida State University, Tallahasse, FL, 1981, Biology
Dr. Eilertsen's research interests and laboratory activities:
During animal development, an epigenetic memory is established in the nucleus of cells that promote tissue-specific gene expression patterns that dictate cell function. Epigenetic memory is heritable and stable, but not irreversible. Reprogramming is a process of changing a differentiated cell to a less differentiated state and involves erasure of epigenetic memory. Reprogramming will lead to the development of reprogrammed human cells that can be applied to cell-based therapies. Other applications include drug discovery, toxicology screening and livestock cloning. Despite immense promise, somatic cell reprogramming still faces a critical challenge. Specifically, every method described to date can be characterized by low efficiency rates ranging from ~0.0006-1%. The low rates of success, which have not improved after a decade of intense research, limit development and application. My lab focuses on understanding mechanisms of reprogramming induced by 1) somatic cell nuclear transfer (SCNT) and 2) dedifferentiating adult somatic and stem/progenitor cells to a state equivalent to an embryonic stem (or, pluripotent) cell. In addition, we are identifying novel methods and approaches to reprogram cells.
Somatic Cell Nuclear Transfer. My lab’s early efforts focused on developing genomic-scale molecular and mathematical models of SCNT induced reprogramming using gene expression patterns derived from preimplantation embryos and somatic donor cell lines. For example, we identified ~360 genes that indicated the likelihood of full term development of cattle embryos produced by SCNT. Similarly, our lab has identified a group of genes that predict whether a cell line is competent to be reprogrammed using SCNT. Our current efforts are focused on identifying epigenetic gene and protein targets and signaling pathways that can be manipulated using a variety of approaches that improve SCNT reprogramming efficiencies. Examples of approaches include the identification and development of small molecules and interfering RNA.
Somatic/Adult/Progenitor cell reprogramming. To further address the challenges of reprogramming, and to eventually realize the promises of this technology, our research program also focuses on elucidating and understanding mechanisms of reprogramming somatic and adult stem/progenitor cells to a pluripotent state (the ability of a cell to differentiate into all tissues of an organism). Ongoing studies include the identification of methods to induce expression of key genes such as Oct4, Sox2 and Nanog; identification of small molecules that improve reprogramming efficiency; development of novel culture conditions; and improving livestock SCNT efficiency by reprogramming donor cells to a less differentiated state.
Biotech and Economic Development. Bioscience has become a high-priority economic development goal throughout the U.S. The field of bioscience encompasses several different activities along a common theme: application of biology and medical knowledge to problems affecting the human or societal condition. Some key 2007 economic findings about the biotechnology sector in the U.S. are: total employment impact is 7.5 million jobs; job growth outpaces the total private sector by over two percent; average annual wages exceed $70K; venture capital investments exceed $11.5 billion; and over 82,000 bioscience-related patents awarded since 2002. [Sources: Bureau of Economic Analysis (BEA); United States Patent and Trademark Office (USPTO); Biotechnology Industry Organization (BIO); Baton Rouge Area Chamber White Paper: Advancing PBRC to Preeminence: Securing Louisiana’s Knowledge-based Economic Foundation.] In 2004, Dr. Eilertsen Co-founded NuPotential Inc. to develop cell reprogramming technology in partnership with PBRC to market. NuPotential has received over $3MM in venture funding (LA1 Fund, Themelios and La Tech Park Fund), $2MM in NIH funding and $300K from a Louisiana Industrial Ties grant.
1. Jeong-Do Kim, Jong S. Rim, Robert Blake, Yong-Hwan Lee, Jaroslaw Staszkiewicz, Ru Gao, Kenneth J. Eilertsen. Chemicals facilitating reprogramming: Targeting the SAM binding site to identify novel methyltransferase inhibitors. In press.
2. Ru Gao1, Jong S. Rim2, Karen L. Strickler2, Christian W. Barnes2, Lettie L. Harkins2, Jaroslaw Staszkiewicz2, Jeffery M. Gimble1, Barbara Gawronska-Kozak3, Gregory H. Leno4, Kenneth J. Eilertsen. Reprogramming mouse ear mesenchymal stem cells (EMSC) expressing the Dlk1-Dio3 imprinted gene cluster. Stem Cell Discovery Vol.3, No.1, 2013.
3. Jong S. Rim, Karen L. Strickler, Christian W. Barnes, Lettie L. Harkins, Jaroslaw Staszkiewicz, Jeffrey M. Gimble, Gregory H. Leno, Kenneth J. Eilertsen. Temporal epigenetic modifications differentially regulate ES cell-like colony formation and maturation. Stem cell Discovery 2(v2) 2012.
4. Sutton GM, Ptitsyn AA, Floyd ZE, Yu G, Wu X, Hamel K, Shah FS, Centanni A, Eilertsen K, Kheterpal I, Newman S, Leonardi C, Freitas MA, Bunnell BA, Gimble JM. Age (Dordr). Biological Aging alters circadian mechanisms in murine adipose tissue depots. Age (Dordr). 2013 Jun;35(3):533-47. doi: 10.1007/s11357-012-9389-7. Epub 2012 Mar 13.
5. Nelida Rodriguez-Osorio, Rodrigo Urrego, Jose B. Cibelli, Kenneth Eilertsen, Erdogan Memili. Reprogramming Mammalian Somatic Cells. Theriogenology. 2012 Dec;78(9):1869-86. doi: 10.1016/j
Jeansonne D, Kirk-Ballard Eilertsen K, Liu Z. Camptothecin Blocks Apoptosis Induced by Paclitaxel in Human Breast and Pancreatic Cancer Cells. (2011) Oncology reports 25:1473-1480.
6. Jong S. Rim1, Karen Strickler1, Christian Barnes1, Lettie Harkins1, Jaroslaw Staszkiewicz1, Rachel Power1, Kenneth J. Eilertsen1,2,±. Screening for Epigenetic Target Genes that Enhance Reprogramming Using Lentiviral Delivered shRNA. Methods Mol Biol. 2011;702:299-316.
7. Jeansonne D, Kirk-Ballard Eilertsen K, Liu Z. Camptothecin Blocks Apoptosis Induced by Paclitaxel in Human Breast and Pancreatic Cancer Cells. (2011) Oncology reports 25:1473-1480.
8. Eilertsen KJ. Challenges to Changing Identity: Persistent Cellular Memory and Epigenetic Redundancy. Proceedings: Biotechnology and Bioinformatics Symposium (2010.
9. "Botanicals as Epigenetic-Modulators for mechanisms contributing to development of Metabolic Syndrome" Kirk H, Cefalu WT, Ribnicky D, Liu Z, Eilertsen KJ. (2008) Metabolism Clinical and Experimental 57 (Suppl 1) S16-S23.
10. The Epigenetics of Adult (Somatic) Stem Cells. Eilertsen KJ, Floyd E, Gimble JM. Stem Cells, Crit Rev Eukaryot Gene Expre 2007:18(3):189-206.
11. Eilertsen, K.J., Power, R.A., Harkins, L.L., Misica, P. Targeting Cellular Memory to Reprogram the Epigenome, Restore Potential, and Improve Development of SCNT Embryos. Animal Rep Sci.(2007) Mar 98 (1-2):129-46.
12. Bing, N., Hoeschele, I., Ye, K., Eilertsen, KJ. Finite Mixed Model Analysis of Microarray Expression Data on Samples of Uncertain Biological Type with Application to Reproductive Efficiency. Veterinary Immunology and Immunopathology 105, 187-196, 2005.
13. Pfister-Genskow, M., Myers, C., Childs, LA., Lacson, JC., Patterson, T., Betthauser, JM., Goueleke, PJ., Koppang., RW., Lange, G., Fisher, P., Watt, SR., Forsberg, EJ., Zheng., Y., Leno., GH., Schultz., RM., Bing., L., Chetia., C., Yang., X., Hoeschele, I., Eilertsen, KJ. Identification of Differentially Expressed Genes in Individual Bovine Preimplantation Embryos Produced by Nuclear Transfer: Improper Reprogramming of Genes Required for Development. Biology of Reproduction 72, 546-555, 2005.
14. Cezar, G., Bartolomei M., Frosberg E., First N., Bishop M., Eilertsen KJ, Genome-wide epigenetic alterations in cloned bovine fetuses, Biology of Reproduction 68, 1009-1014, 2003.
15. Galik P.K., Givens M.D., Stringfellow D.A., Bishop M.D., Eilertsen K.J., and Crichton, E.G. Bovine diarrhea virus (BVDV) and anti-BVDV antibodies in pooled samples of follicular fluid. Theriogenology, 57(4), 2002.
16. Pace, M., Augenstein, M., Betthauser, J., Childs, L., Eilertsen, K., Enos, J., Forsberg, E., Goueleke, P., Graber, D., Kemper, J., Koppang, R., Lange, G., Lesmeister, T., Mallon, K., Mell, G., Misica, P., Pfister-Genskow, M., Strelchenko, N., Voleker, G., Watt, S., and Bishop, M. D. Ontogeny of Cloned Cattle to Lactation, Biology of Reproduction, 67(1):334-339, 2002.
17. Forsberg, E.,Augenstein, M., Betthauser, J., Childs, L., Eilertsen, K., Enos, J., Golueke, P., Graber, D., Kemper, J., Koppang, R., Lange, G., Lesmeister, T., Mallon, K., Mell, G., Misica, P., Pace, M., Pfister-Genskow, M., Strelchenko, N., Voleker, G., Watt, S., and Bishop, M. D. Production of Cloned Cattle from In Vitro Systems, Biology of Reproduction, 67(1):327-333, 2002.