Austin Nakano
Phone: 310-267-1897
Office: 490D BSRB
Lab: 461 BSRB

Education

M.D., Kyoto University, 1993
Ph.D., Kyoto University, 2001

Research Interests

In the developed countries, acquired heart disease is number one killer, and congenital heart disease affects approximately 0.9% of total human births. While the postnatal mammalian heart is the least regenerative of organs, the embryonic heart displays tremendous capacity for proliferation and lineage diversification. Therefore, deeper understanding of cardiogenesis will provide a potential for novel therapeutic approaches to the heart diseases in adults and children. My research goal is to elucidate how the heart forms and how the heart disease develops. The heart is the first functional organ that develops during mammalian embryogenesis. The early-stage mammalian cardiogenesis (up to looping stage) is largely regulated by genetic program and well recapitulates the heart forming process of non-vertebrates and lower vertebrates. The concepts of 1st and 2nd heart field, multipotent cardiac progenitors, and hemogenic endocardium describe the phenomena during early stages. Throughout the postdoc and junior faculty period, I have contributed to this are through the discovery of multipotent Isl1+ cardiac progenitors and hemogenic activity of the endocardium (Research focus 1). As the embryo grows, the heart is required to functionally support the circulation. Therefore, after the looping stage, the heart needs to strike a delicate balance between its genesis and functionality. Inevitably, the non-genetic factors including biomechanical forces and metabolic/nutritional environment become more important for the cardiogenesis during late stage. While more relevant to the stem cell-based therapy and pathomechanisms of congenital heart disease, less explored area, the late-stage cardiogenesis is much less understood. To tackle this unexplored field, I have established a unique human ESC/iPSC differentiation technique in collaboration with a group in Kyoto U Stem Cell Center. In combination with the atrial-specific Sln-Cre mouse line that I established in the past, I am dissecting the genetic and non-genetic contributors of late-stage cardiogenesis (Research focus 2). Finally, the studies of the late-stage cardiogenesis has brought me to the realm of atrial fibrillation research (Research focus 3).

Selected Publications

Sung K, Ding Y, Ma J, Chen H, Huang V, Cheng M, Yang CF, Kim JT, Eguchi D, Di Carlo D, Hsiai TK, Nakano A, Kulkarni RP, "Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping", Sci Rep (2016).

Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, Karumbayaram S, Kumagai-Cresse C, Wang D, Zack JA, Kohn DB, Nakano A, Nelson SF, Miceli MC, Spencer MJ, Pyle AD, "A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells", Cell Stem Cell (2016).

Nakano A, Nakano H, Smith KA, Palpant NJ, "The developmental origins and lineage contributions of endocardial endothelium", Biochim Biophys Acta (2016).

Gao, C. Ren, S. Lee, J. H. Qiu, J. Chapski, D. J. Rau, C. D. Zhou, Y. Abdellatif, M. Nakano, A. Vondriska, T. M. Xiao, X. Fu, X. D. Chen, J. N. Wang, Y., "RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure", J Clin Invest (2015). [link]

Shimura, D. Kusakari, Y. Sasano, T. Nakashima, Y. Nakai, G. Jiao, Q. Jin, M. Yokota, T. Ishikawa, Y. Nakano, A. Goda, N. Minamisawa, S., "Heterozygous deletion of Sarcolipin maintains normal cardiac function", Am J Physiol Heart Circ Physiol (2015). [link]

Lluri, G. Huang, V. Touma, M. Liu, X. Harmon, A. W. Nakano, A., "Hematopoietic progenitors are required for proper development of coronary vasculature", J Mol Cell Cardiol 86: 199-207 (2015). [link]

Kim, P. G. Nakano, H. Das, P. P. Chen, M. J. Rowe, R. G. Chou, S. S. Ross, S. J. Sakamoto, K. M. Zon, L. I. Schlaeger, T. M. Orkin, S. H. Nakano, A. Daley, G. Q., "Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence", J Exp Med (2015). [link]

Shimizu, H. Schredelseker, J. Huang, J. Lu, K. Naghdi, S. Lu, F. Franklin, S. Fiji, H. D. Wang, K. Zhu, H. Tian, C. Lin, B. Nakano, H. Ehrlich, A. Nakai, J. Stieg, A. Z. Gimzewski, J. K. Nakano, A. Goldhaber, J. I. Vondriska, T. M. Hajnoczky, G. Kwon, O. Chen, J. N., "Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity", eLife 4: (2015). [link]

Chen, P. Y. Ganguly, A. Rubbi, L. Orozco, L. D. Morselli, M. Ashraf, D. Jaroszewicz, A. Feng, S. Jacobsen, S. E. Nakano, A. Devaskar, S. U. Pellegrini, M., "Intra-Uterine Calorie Restriction Affects Placental DNA Methylation and Gene Expression", Physiol Genomics 45 (14): 565-576 (2013).

Arshi, A., Nakashima, Y., Nakano, H., Eaimkhong, S. Evseenko, D. Reed, J., Stieg, A.Z. Gimzewski, J. K. Nakano, A., "Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells", Sci Technol Adv Mater 14: (2013). [link]

Sasman, A., Nassano-Miller, C., Shim, K.S., Koo, H.Y., Liu, T., Schultz, K.M., Millay, M., Nanano, A., Kang, M., Suzuki, T., Kume, T.,, "Generation of conditional alleles for Foxc1 and Foxc2 in mice", Genesis 50 (10): 766-774 (2012).

Van Handel, B., Montel-Hagen, A., Sasidharan, R., Nakano, H. Ferrari, R., Boogerd, C.J., Schredelseker, J., Wang, Y., Hunter, S., Org, T., Zhou, J., Li, X., Pellegrini, M. Chen, J.N., Orkin, S.H., Kurdistani, S.K., Evans, S.M., Nakano, A., Mikkola, H.K., "Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium", Cell 150: 590-605 (2012).

Nakano H, Williams E, Hoshijima M, Sasaki M, Minamisawa S, Chien KR, Nakano A., "Cardiac origin of smooth muscle cells in the inflow tract", J Mol Cell Cardiol 50 (2): 337-345 (2011).

Laugwitz, K.L., Moretti, A., Caron, L., Nakano, A. and Chien, K.R., "Islet 1 cardiovascular progenitors: a single source for heart lineages?", Development 135 (2): 193-205 (2008).

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., "Multipotent Embryonic Isll(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification", Cell 127 (6): 1151-1165 (2006).