黄河，研究员，博士生导师，课题组长。工作聚焦于蛋白质新型翻译后修饰研究，一方面发现蛋白新型翻译后修饰及其关键调控因子，并结合临床资源和数据揭示其在疾病演进过程中的作用机制；另一方面，鉴定代谢调节活性天然产物分子的作用靶标，阐释其通过翻译后修饰介导表型的新机制。
代表性研究成果：（1）发现蛋白新型修饰：发现了一种全新动态修饰——赖氨酸乙酰乙酰化及其调控酶HBO1，为基于表观遗传靶标的创新药物研究带来了新方向（Adv Sci, 2023）；（2）揭示蛋白新型修饰调控机制：揭示了 -羟基丁酰化、苯甲酰化和琥珀酰化修饰的关键调控酶，拓展了其修饰底物谱，阐释了上述新型修饰耦合酮体等代谢物与多种细胞进程的新机制（Sci Adv, 2021；iSCIENCE, 2022；Cell Discov, 2023）；（3）探索蛋白新型修饰临床转化：将新型修饰组学引入到临床研究中，系统绘制了肝癌组织乳酰化修饰全景图谱，揭示了乳酰化对肝癌细胞代谢的关键调节作用，发现了腺苷酸激酶2（AK2）可以作为潜在的治疗靶标，为肝细胞癌靶向治疗提供了新思路（Nat Metab, 2023）；（4）阐明药物作用新靶标、新机制：发现了高血脂治疗潜在新靶标HNF-1 ，揭示了小檗碱类天然产物降脂药物DC371739介导转录因子和组蛋白修饰的独特表观遗传调控机制，鉴定了该药物的临床疗效监控生物标志物PCSK9和ANGPTL3（Cell Metab, 2022）。
共发表SCI论文68篇，获得美国授权专利5项。其中以第一或通讯作者（含共同）在Cell、Cell Metab、Nat Metab、Mol Cell、Cell Res、Cell Discov、Sci Adv、Nat Comm、J Am Chem Soc等杂志上发表论文31篇。论文总影响因子848.9，被引用7500余次，H指数39。
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
2012.11–2019.1 美国芝加哥大学，博士后/研究助理
2010.8–2012.10 美国西北大学，博士后
基于蛋白质动态修饰通路的新靶点鉴定及创新药物研究
2022, 中国科学院上海分院第八届杰出青年科技创新人才
代表论著（2010年以后）：
1.Li J#, Lu L#, Liu L#, Ren X, Chen J, Yin X, Xiao Y, Li J, Wei G, Huang H*, Wei W*, Wong J*. HDAC1/2/3 Are Major Histone Desuccinylase Critical for Promoter Desuccinylation. Cell Discov, 2023, Accepted.
2.Gao Y#, Sheng X#, Tan D#, Kim S#, Choi S, Paudel S, Lee T, Yan C, Tan M, Kim KM, Cho SS, Ki SH, Huang H*, Zhao Y*, Lee SK*. Identification of Histone Lysine Acetoacetylation as a Dynamic Post‐Translational Modification Regulated by HBO1. Adv Sci, 2023, 2300032.
3.Yang Z#, Yan C#, Ma J#, Peng P#, Ren X, Cai S, Shen X, Wu Y, Zhang S, Wang X, Qiu S, Zhou J, Fan J, Huang H*, Gao Q*. Lactylome suggests novel mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab., 2023, 5, 61.
4.Tan D, Wei W, Han Z, Ren X, Yan C, Qi S, Song X, Zheng YG, Wong J, Huang H*. HBO1 Catalyzes Lysine Benzoylation in Mammalian Cells. iSCIENCE, 2022, 25, 105443.
5.Wang J#, Zhao J#, Yan C#, Xi C#, Wu C, Zhao J, Li F, Ding Y, Zhang R, Qi S, Li X, Liu C, Hou W, Chen H, Wang Y, Wu D, Chen K, Jiang H, Huang H*, Liu H*. Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial. Cell Metab., 2022, 667.
6.Zeng Y, Shi W, Dong Q, Li W, Zhang J, Ren X, Tang C, Liu B, Song Y, Wu Y, Diao X, Zhou H, Huang H, Tang F, Huang W*. A Traceless Site-Specific Conjugation on Native Antibodies Enables Efficient One-Step Payload Assembly. Angew. Chem. Int. Ed., 2022, 61, e202204132.
7.Huang H#,*, Zhang D #, Weng Y, Delaney K, Tang Z, Yan C, Qi S, Peng C, Cole PA, Roeder RG, Zhao Y*. The regulatory enzymes and protein substrates for the lysine -hydroxybutyrylation pathway. Sci. Adv., 2021, 7, eabe2771.
8.Koronowski K#,*, Greco C#,*, Huang H, Kim J, Fribourgh J, Crosby P, Mathur L, Ren X, Partch C, Jang C, Qiao F, Zhao Y, Sassone-Corsi P. Ketogenesis impact on liver metabolism revealed by proteomics of lysine -hydroxybutyrylation. Cell Rep., 2021, 36, 109487.
9.Shi W#, Tang F#, Ao J, Yu Q, Liu J, Tang Y, Jiang B, Ren X, Huang H, Yang W*, Huang W*. Manipulating the Click Reactivity of Dibenzoazacyclooctynes: From Azide Click Component to Caged Acylation Reagent by Silver Catalysis. Angew. Chem. Int. Ed., 2020, 59, 19940.
10.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.
11.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.
12.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.
13.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.
14.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.
15.Zuzanna Kaczmarska#, Esther Ortega, Afsaneh Goudarzi, He Huang, Sunjoo Kim, Jos A M rquez, Yingming Zhao, Saadi Khochbin, Daniel Panne*. Structure of p300 in complex with acyl-CoA variants. Nat. Chem. Biol. 2017, 13, 21-25.
16.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 -hydroxybutyrylation. Mol. Cell 2016, 62, 194-206.
17.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.
18.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.
19.Inmaculada Mart nez-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.
20.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.
21.He Huang#, Shu Lin, Benjamin A Garcia, Yingming Zhao*. Quantitative proteomic analysis of histone modifications. Chem. Rev. 2015, 115, 2376-2418.
22.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.
23.He Huang#, Benjamin R Sabari, Benjamin A Garcia, C David Allis, Yingming Zhao*. SnapShot: histone modifications. Cell 2014, 159, 458-458.
24.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 M hlhausen, 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.
25.He Huang#, Huiying Li, Sun Yang, Georges Chreifi, Pavel Marta？sek, 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.
26.He Huang#, Huiying Li, Pavel Mart sek, 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.
27.He Huang#, Haitao Ji, Huiying Li, Qing Jing, Kristin Jansen Labby, Pavel Mart sek, 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.
28.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.
29.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 -heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase II catalytic activity. J. Med. Chem. 2010, 53, 3048-3064.
