M.D., Ph.D. Professor Gen Kondoh
Our main research goal is to reveal the molecular mechanism underlying mammalian fertilization. To investigate this biological process, we take biochemical and molecular biological procedures to identify important molecules and perform functional analyses using gene-manipulated animals.
Research and Education
Mammalian sperm undergo multiple maturation steps after leaving testis to be competent for fertilization. Serial important changes occur in the female reproductive tract on sperm, although the molecular mechanisms underlying these processes remain unclear. In our early study, we found that angiotensin-converting enzyme (ACE) releases GPI-anchored proteins (GPI-AP) from the cell membrane and plays a critical role in mammalian fertilization (publication 5). We also found that sperm undergoing GPI-AP release associated with reorganization of lipid raft and acrosome reaction acquire fertilization potential (Figure1 and publication 4). In terms of identifying factors triggering these processes in vivo, we found Lipocaline2 as a sperm maturation factor of female (publication 1). Recently, we started new research projects elucidating character and function of new helper T cell, Th17 cell, to clarify the mechanism of inflammation (publication 2 and 3). We educate graduate students on the mammalian biology of reproduction, immunology and also how to produce gene-manipulated mice.
- Watanabe, H., Takeo, H. Tojo, K. Sakoh, T. Berger, N. Nakagata, T. W. Mak, and G. Kondoh. Lipocalin2 binds to membrane phosphatidylethanolamine to induce lipid raft movement in a PKA-dependent manner and modulates sperm maturation. Development, 141, 2157-2164 (2014).
- Hirota, K., E. Turner, M. Villa, J. H. Duarte, J. Demengeot, O. M. Steinmetz, and B. Stockinger. Plasticity of TH17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol., 4, 372-379 (2013).
- Hirota, K., H. Duarte, M. Veldhoen, E. Hornsby, Y. Li, D. J. Cua, H. Ahlfors, C. Wilhelm, M. Tolaini, U. Menzel, A. Garefalaki, A. J. Potocnik, and B. Stockinger. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol., 12, 255-263 (2011).
- Watanabe, H., and G. Kondoh: Mouse sperm undergo GPI-anchored protein release associated with lipid raft reorganization and acrosome reaction to acquire fertility. J. Cell Sci., 124-15, 2573-2581 (2011).
- Kondoh, G., Tojo, Y. Nakatani, N. Komazawa, C. Murata, K. Yamagata, Y. Maeda, T. Kinoshita, M. Okabe, R. Taguchi and J. Takeda: Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat. Med., 11, 160-166 (2005).
Professor: Gen Kondoh
Associate Professor: Keiji Hirota
Assistant Professor: Hitomi Watanabe