Research Program: Transplant Biology and Therapy
Assistant Professor of Medicine: Hematology, Oncology and Transplant Division

kikyo001@umn.edu
612-624-0498 — office
612-625-1452 — lab
Preferred method of contact: e-mail

Dr. Kikyo is an assistant professor of medicine in the Hematology, Oncology and Transplant Division. He received his M.D. (1987) and his Ph.D. (1993) from the University of Tokyo Medical School. He worked on genomic imprinting in the laboratory of Dr. Azim Surani at the Wellcome/CRC Institute, University of Cambridge as a Sankyo Research Fellow. Dr. Kikyo then started his long-term project on the nuclear reprogramming in frog egg extract at the laboratory of the late Dr. Alan Wolffe at NIH/NICHD. He is a member of the Cancer Center and the Stem Cell Institute, and he is a member of the teaching faculty for the MICaB, MCDB&G and MD/PhD graduate programs. He has served as an ad hoc member of the NIH study section DEV2 and the Special Emphasis Panel for Human Embryonic Stem Cell projects.

Research Interests

Epigenetic regulation of cell differentiation is surprisingly reversible as demonstrated in many vertebrate species by somatic cell nuclear cloning, a procedure to create genetically identical animals by replacing egg nuclei with somatic cell nuclei. The injected nuclei of terminally differentiated cells can be dedifferentiated during this procedure and redifferentiate into a variety of cell types during the subsequent embryogenesis. This procedure clearly demonstrates that powerful nuclear reprogramming factors are present within eggs. Our long-term goal is to identify the nuclear reprogramming factors in eggs and understand the epigenetic mechanisms underlying nuclear plasticity to contribute to the future regenerative medicine. This study is also highly relevant to the epigenetic reprogramming during malignant transformation of the cells.

To identify novel nuclear reprogramming factors, we established an efficient in vitro model for nuclear cloning by combining Xenopus egg extract and somatic cell nuclei. Through this study we have identified the chromatin remodeling ATPase ISWI as a key player for protein release from somatic chromatin (Kikyo et al., 2000). We also purified the nucleolar disassembly factor FRGY2a/b from egg extract and analyzed its mechanism of nucleolar disassembly (Gonda et al., 2003)(Gonda and Kikyo, 2006)(Gonda et al., 2006). More recently, we have found that the histone-binding protein nucleoplasmin can globally decondense chromatin of somatic cells and facilitate activation of new genes (Tamada et al., 2006). We are currently analyzing how these factors contribute to nuclear reprogramming, as well as searching for novel factors from frog egg extract and various stem cells extract. Furthermore, we are investigating how these nuclear reprogramming factors are involved in the transcriptional reprogramming during malignant transformation.

Selected Publications

Kikyo, N., Wade, P.A., Guschin, D., Ge, H. and Wolffe, A.P. (2000) Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science 289, 2360-2362

Wade, P.A. and Kikyo, N. (2002) Chromatin remodeling in nuclear cloning. Eur J Biochem 269, 2284-2287

Gonda, K., Fowler, J., Katoku-Kikyo, N., Haroldson, J., Wudel, J. and Kikyo, N. (2003) Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nature Cell Biol 5, 205-10 (Highlighted in Nature, Nature Cell Biology, Nature Review Mol Cell Biology, Science and J Cell Biology.

Tamada, H. and Kikyo, N. (2004) Nuclear reprogramming in mammalian somatic cell nuclear cloning. Cytogenetics Genome Res, 105, 285-291

Tamada, H., Thuan, N. V., Reed, P., Nelson, D., Katoku-Kikyo, N., Wudel, J., Wakayama, T.and Kikyo, N. (2006) Chromatin decondensation and nuclear reprogramming by nucleoplasmin. Mol Cell Biol 26, 1259-71

Gonda, K., Wudel, J., Nelson, D., Katoku-Kikyo, N., Reed, P, Tamada, H. and Kikyo, N. (2006) Requirement of the protein B23 for nucleolar disassembly induced by the FRGY2a family proteins. J Biol Chem 281, 8153-60

Gonda, K. and Kikyo, N. (2006) Nuclear remodeling assay in Xenopus egg extract. Methods Mol Biol, 348, 247-58

Zhang, L., Rayner, S., Katoku-Kikyo, N., Romanova. L., and Kikyo N. (2007) Successful co-immunoprecipitation of Oct4 and Nanog using cross-linking. Biochem Biophys Res Comm, 361, 611-4

Kikyo, N. (2008) Approaches to identify nuclear reprogramming factors from eggs and embryonic stem cells, in Stem Cells and Regenerative Medicine, ed. Low, W. and Verfaillie, C., World Scientific Publishing, in press.