Nobuaki Kikyo, M.D./Ph.D.

kikyo001@umn.edu

Education

Dr. Kikyo received the degrees of M.D. and Ph.D. from Tokyo University Medical School, Japan.  He studied genomic imprinting in Dr. Azim Surani’s laboratory at Wellcome/CRC Institute, University of Cambridge as a postdoctoral fellow. He then moved to Dr. Alan Wolffe’s laboratory at NIH to start biochemical analysis of somatic cell nuclear cloning in Xenopus.  He is Assistant Professor of Medicine at the University of Minnesota and a member of the Stem Cell Institute since 2000.

Research Interests

Nuclear cloning is a procedure to create genetically identical animals by injecting somatic nuclei into unfertilized eggs.  Recent success in mammalian cloning with differentiated adult nuclei strongly indicates that egg cytoplasm contains unidentified remarkable reprogramming activities with the capability to erase previous memory of cell differentiation. At the heart of this nuclear reprogramming lies chromatin remodeling since chromatin structure and function define cell differentiation through regulation of the transcriptional activities of the cells.  However, despite the long history and current intensive research on nuclear cloning, little is known about the molecular mechanisms responsible for the chromatin remodeling associated with nuclear cloning.  The long-term goal of this group is to understand how differentiated somatic nuclei are dedifferentiated in egg cytoplasm and are redifferentiated during the subsequent embryogenesis. Once the mechanisms are understood, they can be applied for creation of new tissues using patients’ somatic cells for transplantation medicine without using ethically controversial embryonic materials.  

This group has identified three nuclear remodeling factors from Xenopus egg extract.

Chromatin remodeling protein ISWI (Kikyo et al, 2000). ISWI releases the basal transcription factor TBP from somatic nuclei, leading to suppression of transcription from the somatic nuclei in egg extract.  This activity may be important to erase previous transcriptional status of somatic nuclei.   

RNA-binding proteins FRGY2a and FRGY2b (Gonda et al, 2003 and in press).  FRGY2a/b reversibly disassemble somatic cell nucleoli in egg extract through interactions with the nucleolar protein B23.  Functional significance of the nucleolar disassembly in nuclear reprogramming is currently under investigation.

Selected Publicatons

• Kikyo, N., and Wolffe, A. P. (2000) Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons. J Cell Sci. 113, 11-20.
• Kikyo, N., Wade, P. A., Guschin, D. and Wolffe, A. P. (2000) Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science  289, 2360-2.
• Wade, P., 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., Kikyo, N. (2003)  Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nature Cell Biol. 5, 205-10
• Tamada, H., Kikyo, N. (2004) Nuclear reprogramming in mammalian somatic cell nuclear cloning. Cytogenet 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. and Kikyo, N. Nuclear remodeling assay in Xenopus egg extract.  Method Mol Biol in press.

• Gonda, K., Wudel, J., Nelson, D., Katoku-Kikyo, N., Reed, P, Tamada, H. and Kikyo, N. Requirement of the protein B23 for nucleolar disassembly induced by the FRGY2a family proteins. J Biol Chem in press.