Research: The genome is not merely a passive repository of genetic information. Chromosomes are dynamic entities undergoing structural changes that underlie development and cellular differentiation. We are interested in how developmental and environmental cues induce heritable variation in chromatin structure and how these variations regulate developmental potency, cell-fate and gene expression. The development of the fertilized zygote into a complex organism has traditionally been understood as a unidirectional process, with cells in the embryo becoming gradually more committed to a specific tissue type. However, nuclear transfer experiments have demonstrated that the mammalian egg can relieve the constraints imposed by cellular differentiation and return the nucleus of an adult cell to a totipotent embryonic state. This process has been termed nuclear reprogramming. The primary research focus of our group is to understand the mechanisms by which reprogramming occurs. In particular, we wish to determine the nature of epigenetic information that is reprogrammed (i.e., aspects of DNA methylation and chromatin structure), the times at which reprogramming events occur and the identities of the molecular machinery that accomplish reprogramming. In addition, we are using nuclear transfer and other approaches to develop human embryonic stem cell lines that carry the genes responsible for human neurodegenerative disease. It is our hope that these cell lines will provide valuable model systems for the in vitro study of these diseases.
Selected Publications: D. Egli, J. Roasains, G. Birkhoff, K. Eggan. ” Developmental reprogramming after chromosome transfer into mouse zygotes.” Nature. 2007, 447: 679. F.P. Di Giorgio, M. Carrasco. M. Siao, T. Maniatis, K. Eggan. "An embryonic stem cell based model for ALS: Non-cell autonomous affects of glial cells on motor neurons." Nature Neuroscience. 2007. 10:608-614. K.Eggan, S.Jurga, R. Gosden, IM. Min, and AJ. Wagers. "Ovulated oocytes in adult mice derive from non-circulating germ cells." Nature. 2006, 441:1109. X. Yang, K. Eggan, G. Seidel, R. Jaenisch, D. Melton. "A simple system of checks and balances to cut fraud." Nature. 2006 439:782. C.Cowan, J. Atienza, D. Melton and K. Eggan. "Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells." Science, 2005, 309:1369. [Abstract] [Full Text] K. Eggan, K. Baldwin, M. Tackett, J. Gogos, J. Osbourne, A. Chess, R. Axel, R. Jaenisch. “Mice cloned from olfactory sensory neurons.” Nature, 2004, 428: 44. N. Geijsen, M. Horoschak, K. Kim, J. Gribnau, K. Eggan, G.Q. Daly. “Derivation of embryonic germ cells and male gametes from embryonic stem cells.” Nature, 2004, 437: 148. A. Bortvin, K. Eggan, H. Skaletsky, D. Berry, H. Akutsu, R. Yanagimachi, D. Page, R. Jaenisch. “Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei.” Development, 2003, 130: 1673. D. Humpherys, K. Eggan, H. Akutsu, A. Friedman, K. Hochedlinger, R. Yanagimachi, E. Lander, R. Jaenisch. “Abnormal gene expression in cloned mice derived from ES cell and cumulus cell nuclei.” Proceedings of the National Academy of Sciences USA, 2002, 99: 12889. K. Eggan, A. Rhode, I. Jentsch, C. Samuel, T. Hennek, H. Tintrup, B. Zevnik, J. Erwin, J. Loring, L. Jackson-Grusby, M. Speicher, R. Kuehn, R. Jaenisch. “Male and female mice derived from the same ES cell clone by tetraploid embryo complementation.” Nature Biotechnology, 2002, 20: 455. D. Humpherys, K. Eggan, H. Akutsu*, K. Hochedlinger, W. Rideout, D. Biniskiewicz, R. Yanagimachi, R. Jaenisch.“Epigenetic instability in ES cells and cloned mice.” Science, 2001, 293: 95. K. Eggan, H. Akutsu, J. Loring, L. Jackson-Grusby, M. Klemm, W. Rideout, R. Yanagimachi, R. Jaenisch. “Hybrid vigor, fetal overgrowth and the viability of mice derived by nuclear cloning and tetraploid embryo complementation.” Proceedings of the National Academy of Sciences USA , 2001, 98: 6209. K. Eggan, H. Akutsu, K. Hochedlinger, W. Rideout, R. Yanagimachi, R. Jaenisch. “X chromosome inactivation in cloned mouse embryos.” Science, 2000, 290: 1578.
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