黃河，研究員，博士生導(dǎo)師，課題組長。工作聚焦于蛋白質(zhì)新型翻譯后修飾研究，一方面發(fā)現(xiàn)蛋白新型翻譯后修飾及其關(guān)鍵調(diào)控因子，并結(jié)合臨床資源和數(shù)據(jù)揭示其在疾病演進(jìn)過程中的作用機(jī)制；另一方面，鑒定代謝調(diào)節(jié)活性天然產(chǎn)物分子的作用靶標(biāo)，闡釋其通過翻譯后修飾介導(dǎo)表型的新機(jī)制。
代表性研究成果：（1）發(fā)現(xiàn)蛋白新型修飾：發(fā)現(xiàn)了一種全新動態(tài)修飾——賴氨酸乙酰乙?；捌湔{(diào)控酶HBO1，為基于表觀遺傳靶標(biāo)的創(chuàng)新藥物研究帶來了新方向（Adv Sci, 2023）；（2）揭示蛋白新型修飾調(diào)控機(jī)制：揭示了 -羥基丁?；?、苯甲?；顽牾；揎椀年P(guān)鍵調(diào)控酶，拓展了其修飾底物譜，闡釋了上述新型修飾耦合酮體等代謝物與多種細(xì)胞進(jìn)程的新機(jī)制（Sci Adv, 2021；iSCIENCE, 2022；Cell Discov, 2023）；（3）探索蛋白新型修飾臨床轉(zhuǎn)化：將新型修飾組學(xué)引入到臨床研究中，系統(tǒng)繪制了肝癌組織乳?；揎椚皥D譜，揭示了乳酰化對肝癌細(xì)胞代謝的關(guān)鍵調(diào)節(jié)作用，發(fā)現(xiàn)了腺苷酸激酶2（AK2）可以作為潛在的治療靶標(biāo)，為肝細(xì)胞癌靶向治療提供了新思路（Nat Metab, 2023）；（4）闡明藥物作用新靶標(biāo)、新機(jī)制：發(fā)現(xiàn)了高血脂治療潛在新靶標(biāo)HNF-1 ，揭示了小檗堿類天然產(chǎn)物降脂藥物DC371739介導(dǎo)轉(zhuǎn)錄因子和組蛋白修飾的獨特表觀遺傳調(diào)控機(jī)制，鑒定了該藥物的臨床療效監(jiān)控生物標(biāo)志物PCSK9和ANGPTL3（Cell Metab, 2022）。
共發(fā)表SCI論文68篇，獲得美國授權(quán)專利5項。其中以第一或通訊作者（含共同）在Cell、Cell Metab、Nat Metab、Mol Cell、Cell Res、Cell Discov、Sci Adv、Nat Comm、J Am Chem Soc等雜志上發(fā)表論文31篇。論文總影響因子848.9，被引用7500余次，H指數(shù)39。
教育經(jīng)歷：
2004.9–2010.7 中國科學(xué)院上海藥物研究所，博士
2000.9–2004.7 同濟(jì)大學(xué)化學(xué)系，學(xué)士
工作經(jīng)歷：
2019.1至今 中國科學(xué)院上海藥物研究所，研究員 ，課題組長
2012.11–2019.1 美國芝加哥大學(xué)，博士后/研究助理
2010.8–2012.10 美國西北大學(xué)，博士后
基于蛋白質(zhì)動態(tài)修飾通路的新靶點鑒定及創(chuàng)新藥物研究
2022, 中國科學(xué)院上海分院第八屆杰出青年科技創(chuàng)新人才
代表論著（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.
