分子心脏学研究组 研究组长 杨黄恬

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分子心脏学研究组 研究组长 杨黄恬
杨黄恬 研究员  研究组长

htyang@sibs.ac.cn   
 
学习经历

1978-1982   南通医学院 医学学士
1985-1988   苏州医学院 医学硕士
1992-1994   日本山形大学医学部 医学博士 

工作简历

1982-1985   南通医学院 药理教研室助教
1989-1992   南通医学院 药理教研室讲师
1992-1997   日本山形大学医学部药理教研室客座研究员、助手
1997-2001   美国国立卫生研究院/老年研究所(NIH/NIA)心血管研究室/分子心脏学室访问学者
2000-至今   中科院上海生命科学院/上海交通大学医学院 健康科学研究所研究员、课题组组长
2003-2004   中科院上海生命科学院/上海交通大学医学院 健康科学研究所所长助理
2005-至今   中科院上海生命科学院/上海交通大学医学院 健康科学研究所副所长 

荣誊(证书、称号、会员)

1990       中华医学会心血管病学会会员
1992-1993  日本世川医学奖学金
1993-1995  日本Weihala奖学金
1993       日本药理学会会员
2000       中国科学院“百人计划”
2000       中华医学会高原医学分会委员会委员
2001       NIH 研究者优秀研究奖
2001       国际心脏研究学会中国分会会员
2001       上海生理学会理事
2003       中国生理学会理事
2003       中国细胞生物学学会会员
2004       国际心脏研究学会中国分会执委会委员
2004       中国病理生理学会心血管专业委员会执委会委员
2004       上海市科教系统“三八红旗手” 

主要成果

    证明了心肌存在着不同密度和亲和力的a1肾上腺素受体亚型和内皮素受体亚型,揭示了其耦联的IP3信号通路调控心肌收缩力的分子机制;
    建立了Ca2+ 释放通道ryanodine受体2基因剔除小鼠模型和胚胎干细胞系, 向心肌细胞和神经元体外分化、及成体干细胞体外分化的体系和分析手段,从基因水平直接证明了心肌ryanodine受体参与了心肌细胞搏动频率的调控,提示了该受体在心律失常和心脏卒死中的重要性。
    研究组建立了研究胚胎和成体干细胞、尤其是胚胎干细胞向心肌细胞及神经细胞分化的一系列平台;揭示了由胚胎干细胞分化的不同发育期心肌细胞的基因表达和功能特征;利用心肌ryanodine受体剔除的胚胎干细胞,证明了肌浆网在胚胎干细胞早期分化的心肌细胞对Ca2+信号和收缩功能的关键调控作用,为移植胚胎干细胞分化的心肌细胞治疗心肌梗塞的可能性提供了实验依据;利用基因的突变并结合药理学研究策略,探讨了胚胎干细胞向心肌细胞和神经细胞分化及成体干细胞向心肌细胞分化的调控因素和基因及胚胎干细胞移植对心肌梗塞的治疗作用和可能的机制。
    在发现间歇性低氧可有效对抗致死性Ca2+超载导致的心肌损伤的基础上,结合分子生物学、细胞生物学、基因工程、生化、生理、药理学研究手段及基因芯片和蛋白质组学分析方法,对其抗心肌缺血的保护作用机制和调控在提出了新发现,揭示了转录因子、应激蛋白的新功能和肌浆网Ca2+调控蛋白及Ca2+调蛋白激酶的保护作用。这些发现不仅对深入认识低氧适应的内在的细胞分子基础和对应激的防御体系有重要的科学价值, 也为探讨防治缺血性心肌损伤的新靶点和治疗方式提供了实验依据。

主要论文

Gao H, Chen L, Yang HT. Activation of alpha(1B)-adrenoceptors alleviates ischemia/reperfusion injury by limitation of mitochondrial Ca(2+) overload in cardiomyocytes. Cardiovasc Res. 2007 Apr 21; [Epub ahead of print]

Li J, Zhang H, Zhu WZ, Yu Z, Guo A, Yang HT, Zhou ZN. Preservation of the pHi during ischemia via PKC by intermittent hypoxia. Biochem Biophys Res Commun 2007 May 4;356(2):329-33.

Yang WW, Wang ZH, Zhu Y, Yang HT. E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1. Cell Death Differ. 14, 807–817, 2007

Ji-Dong Fu, Jun Li, David Tweedie, Hui-Mei Yu, , Le Chen, Rong Wang, Daniel R. Riordon, Sheryl A. Brugh, Shi-Qiang Wang, Kenneth R. Boheler, Huang-Tian Yang. Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+ transients and contraction in cardiomyocytes derived from embryonic stem cells. FASEB J. 20: 181-183; 2006.

Ji-Dong Fu, Hui-Mei Yu, Rong Wang, Ji Liang, Huang-Tian Yang. Developmental Regulation of Calcium Transients during Cardiomyocyte Differentiation of Mouse Embryonic Stem Cells. Acta Pharmacologica Sinica. Special Issue: Calcium Signaling. 27 (7): 901–910, 2006

Le Chen, Xi-Yuan Lu, Jun Li, Ji-Dong Fu, Zhao-Nian Zhou, Huang-Tian Yang. Intermittent hypoxia protects cardiomyocytes against I/R-induced alterations in Ca2+ homeostasis and contraction via the SR and Na+/Ca2+ exchange mechanisms. Am J Physiol Cell Physiol. 290(4):C1221-C1229, 2006

W-Z Zhu, Y Xie, L Chen, H-T Yang, and Z-N Zhou. Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury. J Mol Cell Cardiol. 40(1):96-106. 2006

Fa-Bao Zhang; Li Li; Bo Fang; Ding-Liang Zhu; Huang-Tian Yang; Ping-Jin Gao. Passage-restricted differentiation potential of mesenchymal stem cells into cardiomyocyte-like cells. Biochemical and Biophysical Research Communications 336: 784-792. 2005

Yan Xie, Zhu Yi,Wei-Zhong Zhu, Le Chen, Zhao-Nian Zhou, Huang-Tian Yang Contribution of phospholamban phosphorylation to the cardioprotection of intermittent hypoxia in ischemia-reperfused rat heart. Am J Physiol Heart Circ Physiol. 288(6):H2594-602,2005

Hai-Lei Ding, Hai-feng Zhu, Jian-wen Dong, Wei-zhong Zhu, Wei-wei Yang, Huang-tian Yang, Zhao-nian Zhou. Inducible nitric oxide synthase contributes to intermittent hypoxia against ischemia/reperfusion injury. Acta Pharmacol. Sin. 26(3):315-22, 2005

Hong Chen, Xi-Yuan Lu, Liang Zhu, MD, Li-Ping Wang, Huang-Tian Yang, Hong-Zhuan Chen, Wen-Jun Yuan. Evidence of paradoxically enhanced heart tolerance to ischemia/reperfusion insult and upregulation of stress proteins in short-term type 1 diabetes. Acta Pharmacol. Sin. 26(7):806-12. 2005

Yan Xie, Wei-Zhong Zhu, Zhao-Nian Zhou, Zhu Yi, Huang-Tian Yang Intermittent high altitude hypoxia protects the heart against lethal Ca2+ overload injury. Life Science 76:559-572, 2004

Wei-Zhong Zhu, Jian-Wen Dong, Hai-Lei Ding, Huang-Tian Yang and Zhao-Nian Zhou. Postnatal development in intermittent hypoxia enhances resistance to myocardial ischemia/reperfusion in male rats. Eur. J. Appl. Physiol. 91(5-6):716-22, 2004

Anna M. Wobus, K Guan, Huang-Tian Yang & Kenneth R. Boheler. Embryonic stem cells as a model to study cardiac,skeletal muscle,and vascular smooth muscle cell differentiation. Methods in Molecular Biology, Vol. 185:127-156, 2002

KR Boheler , J Czyz, D Tweedie, Huang-Tian Yang, Anisimov S.V., Wobus A.W. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ. Res. 91:189-201, 2002

Huang-Tian Yang , David Tweedie, Su Wang, Antonio Guia, Tatiana Vinogradova, Konstantin Bogdanov, Paul D. Allen, Michael D. Stern, Edward G. Lakatta and Kenneth R. Boheler. The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proc. Natl. Acad. Sci. USA. 99: 9225-9230, 2002

Koban MU, Brugh SA, Riordon DR, Dellow KA, Yang HT, Tweedie D, Boheler KR. A distant upstream region of the rat multipartite Na(+)-Ca(2+) exchanger NCX1 gene promoter is sufficient to confer cardiac-specific expression. Mech Dev. 109(2):267-79, 2001

Huang-Tian Yang , Kiyoharu sakurai, Hiromi Sugawara, Tomoo Watanabe, Ikuo Norota & Masao Endoh. Contribution of Na+/Ca2+ exchange to the endothelin-1-induced increases in Ca2+ transient and contractility in rabbit ventricular cardiac myocytes: pharmacological analysis with KB-R7943. Br. J. Pharmacol. 126: 1785-1795, 1999

Michail D. Stern, Long-Sheng Song, Heping Cheng, James S. K. Sham, Huang-Tian Yang, Kenneth R. Boheler and Eduardo Rios. Local control models of cardiac excitation-contraction coupling: a possible role for allosteric interactions between ryanodine receptors. J. Gen. Physiol. 113:469-489, 1999

Endoh, M., Maruya, J., Norota, I., Yang, H.-T., Talukder, M.A. Hassan, Watanabe, T., Sakurai, K. Cardiac effects of endothelin: difference between signal myocytes and intact ventricular myocardium. Current Topics in Pharmacology 4: 293-300, 1998

Masao Endoh, Shinji Fujita, Huang-Tian Yang, M.A. Hassan Talukder, Jun Maruya and Ikuo Norota. Endothelin: recetpor subtypes, signal transduction, regulation of Ca2+ transients and contractility in rabbit ventricular myocardium. Life Sciences. 62(17/18): 1485-1489, 1998

Y. Zhu, H.-T. Yang & M. Endoh: Does nitric oxide contribute to the negative choronotropic and inotropic effects of endothelin-1 in the heart? Eur. J. Pharmacol. 332: 195-199, 1997

Huang-Tian Yang & Masao Endoh. Pharmacological evidence for a1D-adrenoceptors in the rabbit ventricular myocardium: analysis with BMY 7378. Br. J. Pharmacol. 122: 1541-1550, 1997

Yi Zhu, Huang-Tian Yang and Masao Endoh: Negative chronotropic and inotropic effects of endothelin isopeptides in mammalian cardiac muscle. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H119 - H127 , 1997

Huang-Tian Yang, Yi Zhu and Masao Endoh. Species-dependent differences in inotropic effects and phosphoinositide hydrolysis induced by endothelin-3 in relation to specific binding sites in mammalian ventricular myocardium. Br. J. Pharmacol. 120: 1497 - 1504, 1997

Huang-Tian Yang & Masao Endoh. (±)-Tamsulosin, an a1A-adrenoceptor antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart. Eur. J. Pharmacol. 312(3): 281-291, 1996

Masao Endoh, Ikuo Norota, Huang-Tian Yang, Shinji Fujita and Masahiro Takanashi. Positive inotropic effect and the hydrolysis of phosphoinositide induced by endothelin-3 in rabbit ventricular myocardium: inhibition by a selective antagonist of ETA receptors, FR139317. J. Pharmacol. Exp. Ther. 277(1): 61-71, 1996

Huang-Tian Yang, Ikuo Norota, Yi Zhu and Masao Endoh. Methoxamine-induced inhibition of the positive inotropic effect of endothelin via a1-adrenoceptors in the rabbit heart. Eur. J. Pharmacol 296(1): 47-54, 1996

Huang-Tian Yang , Ikuo Norota, Yi Zhu and Masao Endoh. Mechanisms for the inhibitory action of methoxamine on the receptor-mediated inotropic response. Heart 27(Suppl. 2): 16-19, 1995

Huang-Tian Yang , Ikuo Norota and Masao Endoh. Positive inotropic effect and acceleration of phosphoinositide hydrolysis by methoxamine. Heart 26(Suppl. 4): 24-28, 1994

Yang, Huang-Tian., Yang, Yu-Lin. Study of alpha-1 adrenoceptors in heart: mechanisms of positive inotropic effects and receptor subtypes. Chinese Pharmacological Bulletin. 10:411-414, 1994

Huang-Tian Yang and Masao Endoh. Dissociation of the methoxamine-induced positive inotropic effect and phosphoinositide hydrolysis in rabbit ventricular myocardium: comparison with phenylephrine and alpha-1 adrenoceptor subtype involved. J. Pharmacol. Exp. Ther. 269(2): 732-742, 1994

Kohi M., Yang HT., Endoh M. Myocardial a1A-adrenoceptor subtypes in rabbit: differentiation by a selective antagonist, HV723. Eur. J. Pharmacol. 250: 95-101, 1993

Yang, Huang-Tian., Yang, Yu-Lin., Peng, Si-Xun. and Huang, Wen-Long. Hypotensive effect of naphthylmethyl isoquinoline. Acta Pharmaceutica Sinica. 25(7): 551-554, 1990

Yang, Huang-Tian., Yang, Yu-Lin. Effect of naphthylmethyl isoquinoline on the isolated guinea pig myocardium. Acta Pharmaceutica Sinica. 25(7): 485-489, 1990

专著与综述

Huang-Tian Yang, Zhao-Nian Zhou, Le Chen:
Effects and mechanism of hypoxia on cardiovascular function.
In Cardiovascular Physiology: Basic Science and Clinical Relevance. High Education Press,
China, 2004

实验室简介