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研究队伍
姓 名:
 黄河
性 别:
 男
职 称:
 研究员
学 历:
 博士研究生
电 话:
 +86-21-50800161
传 真:
 +86-21-50800161
电子邮件:
 hhuang@simm.ac.cn
个人主页:
通讯地址:
 上海市浦东张江祖冲之路555号 201203
简历:

黄河,研究员,课题组长。主要从事化学生物学和蛋白质组学研究,研究内容包括蛋白质动态修饰通路的发现与调控机制阐释,以及抗肿瘤小分子抑制剂开发。代表性研究成果:(1)首次发现了一种芳香酰化组蛋白动态修饰——赖氨酸苯甲酰化及其调控酶,并初步阐明其表观遗传调控规律,表明该修饰是特定病理变化过程中的重要表观遗传调控因子;(2)系统地鉴定了蛋白赖氨酸二羟基异丁酰化修饰的调控酶和底物,揭示了p300通过改变蛋白二羟基异丁酰化修饰水平来调控细胞糖代谢的全新机理;(3)系统性地分析复杂的组蛋白动态修饰,绘制了迄今最为全面的组蛋白修饰图谱。共发表SCI论文51篇,获得美国授权专利5项。其中以第一作者或通讯作者在Cell、Chem Rev、Mol Cell、Cell Res、Nat Commun、J Am Chem Soc、Proteomics等杂志上发表论文24篇。论文总影响因子474,被引用3800余次,H指数31。

教育经历:

2004.9–2010.7   中国科学院上海药物研究所,博士

2000.9–2004.7   同济大学化学系,学士

工作经历:

2019.1至今        中国科学院上海药物研究所,研究员 ,课题组长

2015.9–2019.1    美国芝加哥大学,研究助理

2012.11–2015.8   美国芝加哥大学,博士后

2010.8–2012.10   美国西北大学,博士后


研究方向:

基于蛋白质动态修饰通路的新靶点鉴定及创新药物研究


专家类别:
研究员

职务:
课题组长

科研成果:

1.在哺乳动物细胞中发现和确证了一种全新蛋白质动态修饰——赖氨酸苯甲酰化,并成功鉴定了22个组蛋白赖氨酸苯甲酰化位点及其调控酶SIRT2。该修饰是目前已知的唯一一个赖氨酸芳香烃酰化修饰,并显示出独特的生物学功能。针对该修饰的定量蛋白质组学和深度测序结果显示它与多种疾病代谢通路和基因活化密切相关。因该修饰水平升高而导致的基因表达上调与慢性肾衰竭等多种肾脏疾病呈显著相关性。这些结果表明该修饰可能是特定病理变化过程中的一种重要表观遗传调控因子,因此该项研究为基于表观遗传靶点的创新药物研究带来新的方向并将产生重要影响。

2.鉴定出调控蛋白二羟基异丁酰化修饰的关键酶(p300, Tip60,HDAC2和HDAC3)及其在哺乳动物细胞中的修饰底物谱。利用定量蛋白质组学技术鉴定了肿瘤细胞中受p300选择性调控的二羟基异丁酰化修饰底物,并揭示了p300通过改变蛋白二羟基异丁酰化修饰水平来进行细胞糖代谢调控的全新机理,从而阐明了该动态修饰调节细胞代谢的机制。


承担科研项目情况:

社会任职:

获奖及荣誉:

1.中国科学院院长优秀奖(2010年)
2.上海市高等学校优秀毕业生(2010年)
3.礼来亚洲优秀学位论文一等奖(2010年)


代表论著:

代表论著(2010年以后):

1.Di Zhang#, Zhanyun Tang#, He Huang, Guolin Zhou, Chang Cui, Yejing Weng, Wenchao Liu, Sunjoo Kim, Sangkyu Lee, Mathew Perez-Neut, Jun Ding, Daniel Czyz, Rong Hu, Zhen Ye, Maomao He, Y George Zheng, Howard A Shuman, Lunzhi Dai, Bing Ren, Robert G Roeder, Lev Becker*, Yingming Zhao*. Metabolic regulation of gene expression by histone lactylation. Nature 2019, 574, 575.

2.He Huang#, Di Zhang, Yi Wang, Mathew Perez-Neut, Zhen Han, Y. George Zheng, Quan Hao, Yingming Zhao*. Lysine benzoylation is a histone mark regulated by SIRT2. Nat. Commun. 2018, 9, 3374.

3.He Huang#, Shuang Tang#, Ming Ji#, Zhanyun Tang, Miho Shimada, Xiaojing Liu, Shankang Qi, Jason W Locasale, Robert G Roeder, Yingming Zhao*, Xiaoling Li*. EP300-Mediated Lysine 2-Hydroxyisobutyrylation Regulates Glycolysis. Mol. Cell 2018, 70, 663-678.

4.He Huang#, Zhouqing Luo#, Shankang Qi#, Jing Huang#, Peng Xu, Xiuxuan Wang, Li Gao, Fangyi Li, Jian Wang, Wenhui Zhao, Wei Gu, Zhucheng Chen, Lunzhi Dai*, Junbiao Dai*, Yingming Zhao*. Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway. Cell Res. 2018, 28, 111-125.

5.Jing Huang#, Zhouqing Luo#, Wantao Ying#, Qichen Cao, He Huang, Junkai Dong, Qingyu Wu, Yingming Zhao, Xiaohong Qian*, Junbiao Dai*. 2-Hydroxyisobutyrylation on histone H4K8 is regulated by glucose homeostasis in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 8782-8787.

6.Zuzanna Kaczmarska#, Esther Ortega, Afsaneh Goudarzi, He Huang, Sunjoo Kim, José A Márquez, Yingming Zhao, Saadi Khochbin, Daniel Panne*. Structure of p300 in complex with acyl-CoA variants. Nat. Chem. Biol. 2017, 13, 21-25.

7.Zhongyu Xie#, Di Zhang#, Dongjun Chung#, Zhanyun Tang, He Huang, Lunzhi Dai, Shankang Qi, Jingya Li, Gozde Colak, Yue Chen, Chunmei Xia, Chao Peng, Haibin Ruan, Matt Kirkey, Danli Wang, Lindy M. Jensen, Oh Kwang Kwon, Sangkyu Lee, Scott D Pletcher, Minjia Tan, David B Lombard, Kevin P White, Hongyu Zhao, Jia Li, Robert G Roeder, Xiaoyong Yang*, Yingming Zhao*. Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation. Mol. Cell 2016, 62, 194-206.

8.Yuanyuan Li#, Benjamin R Sabari#, Tatyana Panchenko#, Hong Wen, Dan Zhao, Haipeng Guan, Liling Wan, He Huang, Zhanyun Tang, Yingming Zhao, Robert G Roeder, Xiaobing Shi, C. David Allis*, Haitao Li*. Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain. Mol. Cell 2016, 62, 181-193.

9.Afsaneh Goudarzi#, Di Zhang#, He Huang, Sophie Barral, Oh Kwang Kwon, Shankang Qi, Zhanyun Tang, Thierry Buchou, Anne-Laure Vitte, Tieming He, Zhongyi Cheng, Emilie Montellier, Jonathan Gaucher, Sandrine Curtet, Alexandra Debernardi, Guillaume Charbonnier, Denis Puthier, Carlo Petosa, Daniel Panne, Sophie Rousseaux, Robert G Roeder, Yingming Zhao*, Saadi Khochbin*. Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters. Mol. Cell 2016, 62, 169-180.

10.Inmaculada Martínez-Reyes#, Lauren P Diebold, Hyewon Kong, Michael Schieber, He Huang, Christopher T Hensley, Manan M Mehta, Tianyuan Wang, Janine H Santos, Richard Woychik, Eric Dufour, Johannes N Spelbrink, Samuel E Weinberg, Yingming Zhao, Ralph J De Berardinis, Navdeep S Chandel*. TCA cycle and mitochondrial membrane potential are necessary for diverse biological functions. Mol. Cell 2016, 61, 199-209.

11.Benjamin R Sabari#, Zhanyun Tang, He Huang, Vladimir Yong-Gonzalez, Henrik Molina, Ha Eun Kong, Lunzhi Dai, Miho Shimada, Justin R Cross, Yingming Zhao, Robert G. Roeder, C. David Allis*. Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Mol. Cell 2015, 58, 203-215.

12.He Huang#, Shu Lin, Benjamin A Garcia, Yingming Zhao*. Quantitative proteomic analysis of histone modifications. Chem. Rev. 2015, 115, 2376-2418.

13.Jeffrey K Holden#, Soosung Kang, Scott A Hollingsworth, Huiying Li, Nathan Lim, Steven Chen, He Huang, Fengtian Xue, Wei Tang, Richard B Silverman, Thomas L. Poulos*. Structure-based design of bacterial nitric oxide synthase inhibitors. J. Med. Chem. 2015, 58, 994-1004.

14.He Huang#, Benjamin R Sabari, Benjamin A Garcia, C David Allis, Yingming Zhao*. SnapShot: histone modifications. Cell 2014, 159, 458-458.

15.Minjia Tan#, Chao Peng#, Kristin A Anderson#, Peter Chhoy, Zhongyu Xie, Lunzhi Dai, Jeongsoon Park, Yue Chen, He Huang, Yi Zhang, Jennifer Ro, Gregory R. Wagner, Michelle F. Green, Andreas S. Madsen, Jessica Schmiesing, Brett S. Peterson, Guofeng Xu, Olga R. Ilkayeva, Michael J. Muehlbauer, Thomas Braulke, Chris Mühlhausen, Donald S. Backos, Christian A. Olsen, Peter J. McGuire, Scott D. Pletcher, David B. Lombard, Matthew D. Hirschey*, Yingming Zhao*. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014, 19, 605-617.

16.He Huang#, Huiying Li, Sun Yang, Georges Chreifi, Pavel Martasek, Linda J Roman, Frank L Meyskens, Thomas L Poulos*, Richard B Silverman*. Potent and selective double-headed thiophene-2-carboximidamide inhibitors of neuronal nitric oxide synthase for the treatment of melanoma. J. Med. Chem. 2014, 57, 686-700.

17.He Huang#, Huiying Li, Pavel Martásek, Linda J Roman, Thomas L Poulos*, Richard B Silverman*. Structure-guided design of selective inhibitors of neuronal nitric oxide synthase. J. Med. Chem. 2013, 56, 3024-3032.

18.He Huang#, Haitao Ji, Huiying Li, Qing Jing, Kristin Jansen Labby, Pavel Martásek, Linda J Roman, Thomas L Poulos*, Richard B Silverman*. Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations. J. Am. Chem. Soc. 2012, 134, 11559-11572.

19.Qian Ba#, Miao Hao#, He Huang#, Junmei Hou, Shichao Ge, Zhuzhen Zhang, Jun Yin, Ruiai Chu, Hualiang Jiang, Fudi Wang, Kaixian Chen, Hong Liu*, Hui Wang*. Iron deprivation suppresses hepatocellular carcinoma growth in experimental studies. Clin. Cancer Res. 2011, 17, 7625-7633.

20.He Huang#, Qin Chen#, Xin Ku, Linghua Meng*, Liping Lin, Xiang Wang, Caihua Zhu, Yi Wang, Zhi Chen, Ming Li, Hualiang Jiang, Kaixian Chen, Jian Ding, Hong Liu*. A series of α-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase IIα catalytic activity. J. Med. Chem. 2010, 53, 3048-3064.