Atsushi Nakano, M.D., Ph.D.

Laboratory Address:
457 BSRB

Mailing Address:
UCLA Mol, Cell & Dvlmt Bio
BOX 951606, 490D BSRB
Los Angeles, CA 90095

Office Address:
490D BSRB

Affiliations
Affiliations
Assistant Professor, Molecular, Cell, and Developmental Biology
Member, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research
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.
Biography

Austin Nakano got his MD and PhD in Kyoto University, Japan, and has 4 years of clinical experience as a cardiologist. He has had postdoc training at Harvard University/Massachusetts General Hospital/Harvard Stem Cell Institute until he was recruited as an assistant professor at UCLA in 2008. His research focuses on the developmental biology and stem cell biology of the heart. He has been attraceted by the beauty of the morphogenesis of the heart. Although recent progress in the developmental biology of the heart has been revealed the lineage diversity of the cardiac progenitors, it has been difficult to dissect the cellular and molecular mechanisms underlying the process of specification, multipotency, proliferation, differentiation and plasticity of these diverse compotents of the heart. Austin has established a culture system to grow embryonic cardiac progenitor cells in vitro using cardiac mesenchymal feeder system, and several genetically modified mice that label specific cardiac progenitor populations. Using a combination of these unique system and orthodox methodologies, Austin is attempting to understand the art of cardiogenesis at the cellular level.

Publications
Nakano, A. Nakano, H. Chien, K. R. Multipotent Islet-1 Cardiovascular Progenitors in Development and Disease. Cold Spring Harb Symp Quant Biol 2009; (e-pub): .
Laugwitz, K. L. Moretti, A. Caron, L. Nakano, A. Chien, K. R. Islet1 cardiovascular progenitors: a single source for heart lineages?. Development. 2008; 135(2): 193-205.
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. Collaborative roles of gammaH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair. DNA Repair (Amst). 2007; 6(3): 280-92.
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. Chien, K. R. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell. 2006; 127(6): 1151-65 *=equal contribution.
Seo, S. Fujita, H. Nakano, A. Kang, M. Duarte, A. Kume, T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol. 2006; 294(2): 458-70.
Kitaura-Inenaga, K. Hara, M. Higuchi, K. Yamamoto, K. Yamaki, A. Ono, K. Nakano, A. Kinoshita, M. Sasayama, S. Matsumori, A. Gene expression of cardiac mast cell chymase and tryptase in a murine model of heart failure caused by viral myocarditis. Circ J. 2003; 67(10): 881-4.
Ito, H. Nakano, A. Kinoshita, M. Matsumori, A. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia/reperfusion injury in a rat model. Lab Invest. 2003; 83(12): 1715-21.
Adachi, O. Nakano, A. Sato, O. Kawamoto, S. Tahara, H. Toyoda, N. Yamato, E. Matsumori, A. Tabayashi, K. Miyazaki, J. Gene transfer of Fc-fusion cytokine by in vivo electroporation: application to gene therapy for viral myocarditis. Gene Ther. 2002; 9(9): 577-83.
Nakano, A. Matsumori, A. Kawamoto, S. Tahara, H. Yamato, E. Sasayama, S. Miyazaki, J. I. Cytokine gene therapy for myocarditis by in vivo electroporation. Hum Gene Ther. 2001; 12(10): 1289-97.
Ohashi, N. Matsumori, A. Furukawa, Y. Ono, K. Okada, M. Iwasaki, A. Miyamoto, T. Nakano, A. Sasayama, S. Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury. Arterioscler Thromb Vasc Biol. 2000; 20(12): 2521-6.
Sakanoue, Y. Nakano, A. Izumi, C. Inoko, M. Kitaguchi, S. Himura, Y. Iga, K. Gen, H. Konishi, T. Aortic regurgitation in a patient with primary antiphospholipid syndrome--a case report. Jpn Circ J. 1998; 62(3): 228-30.
Nakano, A. Konishi, T. Long term follow-up in a case of anomalous origin of the left coronary artery from the pulmonary artery. Int J Cardiol. 1998; 65(3): 301-3.
Iga, K. Izumi, C. Nakano, A. Sakanoue, Y. Miyamoto, T. Kitaguchi, S. Himura, Y. Gen, H. Konishi, T. Problems in pharmacological evaluation of patients with paroxysmal atrial fibrillation: clinical analysis of more than 100 consecutive patients. Intern Med. 1998; 37(12): 1005-8.
Iga, K. Izumi, C. Nakano, A. Sakanoue, Y. Kitaguchi, S. Himura, Y. Gen, H. Konishi, T. Problems in the initial diagnosis of renal infarction. Intern Med. 1997; 36(5): 330-2.