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Department of Molecular Physiology


Director Osamu NAKAGAWA
Laboratory Chief Yusuke WATANABE, Tomoe Y. NAKAMURA-NISHITANI, Akihiro URASAKI
Research Fellow Daiki SEYA, Toru TANAKA, Norika LIU
Graduate Student Dai IHARA, Yukihiro HARADA
Research Assistant Natsuko YOSHIDA, Nami NAGATA
Visiting Researcher Teruhisa KAWAMURA, Yuichiro ARIMA


Research theme

We are studying the mechanisms of cardiovascular development and its implication in human diseases, mainly focusing on the Notch signaling pathway, bone morphogenetic protein (BMP)-ALK1 receptor signaling pathway, and their downstream target genes such as those encoding the HEY family of transcription factors, the endothelial transmembrane protein TMEM100 and the protein kinase SGK1, among others. We are particularly interested in transcriptional regulation of endothelial and cardiac gene expression, and are also working on other transcription factors such as NKX2-5, ISL1 and the TBX family proteins. In addition, we are trying to extend our research to human cardiovascular diseases in which Notch and BMP-ALK1 signaling plays important roles for the pathogenesis and pathophysiology.

Related publication

  • Araki M, et al., Serum/glucocorticoid-regulated kinase 1 as a novel transcriptional target of bone morphogenetic protein-ALK1 receptor signaling in vascular endothelial cells. Angiogenesis 2018.
  • Fujita M, et al. Pharyngeal arch artery defects and lethal malformations of the aortic arch and its branches in mice deficient for the Hrt1/Hey1 transcription factor. Mech Dev 2016.
  • Mizuta K, et al. Impairment of endothelial-mesenchymal transformation during atrioventricular cushion formation in Tmem100 null embryos. Dev Dyn 2015.
  • Morioka T, et al. An important role of endothelial Hairy-related transcription factors in mouse vascular development. genesis 2014.
  • Somekawa S, et al. Tmem100, an ALK1 signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis. Proc Nat Acad Sci USA 2012.
  • Watanabe Y, et al. Fgf10 regulation in the second heart field by Tbx1, Nkx2-5 and Islet1 reveals a genetic switch for down-regulation of transcription in the myocardium. Proc Natl Acad Sci U S A 2012.
  • Watanabe Y, et al. Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial pole of the heart and pharyngeal arch arteries. Circ Res 2010.
  • Park EJ*, Watanabe Y*, et al. (* Equal contribution) An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. Development 2008.
  • Xin M, et al. Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc Nat Acad Sci USA 2007.
  • Watanabe Y, et al. Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse. Development 2006.
  • Murakami M, et al. A WW domain protein TAZ is a critical co-activator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Nat Acad Sci USA 2005.
  • Kathiriya IS, et al. Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism. J Biol Chem 2004.
  • Gottlieb PD, et al. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nature Genet 2002.
  • Nakagawa O, et al. Members of the HRT family of bHLH proteins act as transcriptional repressors downstream of Notch signaling. Proc Nat Acad Sci USA 2000.

Education and Training

We are dedicated to education and training of young biomedical scientists and physician/scientists. We have affiliated graduate school programs with Nara Medical University, Ritsumeikan University and Osaka University, and also have a postdoctoral training program for biomedical studies in which the stipend and research fund are supplied.

Information and Contact

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