Education
M.D., , Kyoto University 1993
Ph.D., , Kyoto University 2001
Research Interests
The mammalian heart is a complex multi-chambered pump. The proper function of the heart requires highly coordinated process of differentiation and integration of each cellular component. Through the continuing evolutionary selection the cardiac morphogenesis process has been modified and fine tuned to eventually make the miracle of mammalian cardiogenesis. For more than three decades, researchers have been studying how artistic and miraculous this morphogenesis event is. The recent advances in forward and reverse molecular genetics have added a new dimension to the understanding of the cardiogenesis - as represented by discoveries of key transcription factors and diverse cell lineages contributing to the formation of the heart, the developmental biology of the heart has had a great progress over the past decade. However, our understanding of how a highly diverse and specialized subset of heart cell lineages arises from mesodermal precursors and subsequently is assembled into distinct muscle chambers, coronary arterial tree and large vessels, valvular tissue, and conduction system/pacemaker cells remains at a relatively primitive stage. The overall goal of our research is to understand the art of the cardiogenesis from stem cell perspective and uncover the fundamental mechanism of heart formation that cannot be answered simply by molecules and morphology. The key questions we would like to address are; (1) How the commitment and diversification of the cardiac cells is regulated at each level of cardiogenesis (2) How plastic the heart cells are and what is the biological significance of the plasticity during cardiac morphogenesis and disease development (3) What is the molecular mechanism that makes the adult cardiomyocytes terminally differentiated and unable to divide To answer these key questions, we will take both orthodox and new approaches, each of which is not complete by itself but complementary when combined together; (1) Mouse genetic models: Knockout and transgenic mouse models are instrumental for uncovering the role of genes of interest as well as for labeling cells of interest during the cardiogenesis and disease development. (2) Embryonic stem cells: ES cells are not only an in vitro model for embryogenesis but also a limitless source for cardiac progenitors that can be used to screen genes, chemicals and drugs. Human ES and iPS will allow us to validate the discoveries in the human context. (3) Cardiac feeder system: Compared with the stem cell biology of the other organ systems, the stem cell biology of the heart has stayed far behind partly due to the lack of efficient culture system. The cardiac feeder system allows us to answer many important questions in the developmental biology and the stem cell biology of the heart. In most of the developed countries, acquired heart disease has been number one killer, and inherited heart diseases occur in approximately 1% of the live born neonates. Discovery of the cellular dynamism and the underlying molecular mechanisms will provide potential for novel preventive and therapeutic approaches to the heart diseases in adult and children.
Selected Publications
Laugwitz, K.L., Moretti, A., Caron, L., Nakano, A. and Chien, K.R.. 2008. Islet 1 cardiovascular progenitors: a single source for heart lineages? Development 135: 193-205 .
Moretti, A.*, Caron, L.*, Nakano, A.*, Lam, J.T., Bernshausen, A., Chen, Y., Qyang, Y., Bu, L., Sasaki, M., Martin-Puig, S., Sun, Y., Evans, S.M., Laugwitz, K.L. and Chien, K.R.. 2006. Multipotent Embryonic Isll(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification Cell 127: 1151-1165 .
Sonoda, E., Zhao, G.Y., Kohzaki, M., Dhar, P.K., Kikuchi, K., Redon, C., Pilch, D.R., Bonner, W.M., Nakano, A., Watanabe, M., Nakayama, T., Takeda, S., Takami, Y.. 2006. Collaborative roles of gammaH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair DNA Repair (Amst) : - .
Seo, S., Fujita, H., Nakano, A., Kang M., Duarte, A., Kume, T.. 2006. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development Dev Biol 294: 458-470 .
Ito, H., Nakano, A., Kinoshita, M., Matsumori, A.. 2003. Pioglitazone, a peroxisome proliferators-activated receptor-gamma agonist, attenuates myocardial ischemia/reperfusion injury in a rat model Lab Invest 83: 1715-1721 .
Kitaura-Ikenaga, K., Hara, M., Higuchi, K., Yamamotok K., Yamaki, A., Ono, K., Nakano, A., Kinoshita, M., Sasayama S., Matsumori, A.. 2003. Gene expression of cardiac mast cell chymase and tryptase in a murine model of heart failure caused b viral myocarditis Circ J 67: 881-884 .
Adachi, O., Nakano, A., Sato, O., Kawamoto, S., Tahara, H., Toyoda, N., Yamato, E., Matsumori, A., Tabayashi, K., Miyazaki, J.. 2002. Gene transfer of Fc-fusion cytokine by in vivo electroporation: application to gene therapy for viral myocarditis Gene Ther 9: 577-583 .
Nakano, A., Matsumori, A.. 2002. Therapeutic use of Interleukin-10 for myocarditis Fulminant Myocarditis : - .
Nakano, A., Matsumori, A., Kawamoto, S., Tahara, H., Yamato, E., Sasayama, S., Miyazaki, J.. 2001. Cytokine Gene Therapy for Myocarditis by in Vivo Electroporation Hum Gene Ther 12: 1289-1297 .
Kawamoto, S., Nitta, Y., Tashiro, F., Nakano, A., Yamato, E., Tahara, H., Tabayashi, K., Miyazaki, J.. 2001. Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral interleukin-10 International Immunology 13: 685-697 .