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个人简介

1993-1997山东大学微生物学系 学士 1997-2003中国科学院生物物理研究所 博士 2003-2005纪念斯隆-凯特琳癌症中心 博士后助理研究员 2005-2006纪念斯隆-凯特琳癌症中心 博士后副研究员 2006-2010纪念斯隆-凯特琳癌症中心 高级研究科学家 2010-2016清华大学医学院 副教授 2016- 至今 清华大学医学院 教授

研究领域

表观遗传调控的分子结构基础。表观遗传调控关注染色质层面遗传信息组织与解读,具体机制涉及到组蛋白或DNA/RNA修饰、组蛋白变体、染色质重塑以及非编码RNA等。表观遗传机制在从基因表达调控到细胞命运决定等众多生命过程中发挥着重要作用。与此同时,越来越多证据揭示表观遗传调控异常会导致各种人类疾病的发生,尤其是癌症。我们主要采用结构生物学手段,并结合其它生物化学和细胞生物学技术,研究表观遗传调控和修饰生物学过程中的分子识别与催化事件。此外,我们也在积极开展基于微阵列芯片的生物分子互作工具开发和基于结构的药物发现研究。

近期论文

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Zhao S, Chuh KN, Zhang B, Dul BE, Thomson RE, Farrelly LA, Liu X, Xu N, Xue Y, Roeder RG, Maze I*, Muir TW*, and Li H* (2021) Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout. Proc Natl Acad Sci USA (https://doi.org/10.1073/pnas.2016742118) Ren X, Zhao Y, Xue Z, Hao N, Li Y, Guo X, Wang D, Shi X, and Li H* (2021) Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins. Nucleic Acids Res 49: 114-126 Jiang Y, Chen G, Li XM, Liu S, Tian G, Li Y*, Li X*, Li H* and Li XD* (2020) Selective targeting of AF9 YEATS domain by cyclopeptide inhibitors with preorganized conformation. J Am Chem Soc 142: 21450–21459 Zhao F, Liu Y, Su X, Lee JE, Song Y, Wang D, Ge K, Gao J, Zhang MQ, and Li H* (2020) Molecular basis for histone H3 “K4me3-K9me3/2” methylation pattern readout by Spindlin1. J Biol Chem 295: 16877-16887 Armache A, Yang S, Eobbins LE, Durmaz C, Daman AW, Jeong JQ, Marinez de Paz A, Ravishankar A, Arslan T, Lin S, Panchenko T, Garcia BA, Hake SB, Allis CD, Li H*, and Josefowicz SZ* (2020) Histone H3.3 phosphorylation amplifies stimulation-induced transcription. Nature 583: 852–857 Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP, Alderman III MH, Guo C, Wang P, Zhang M, Min W, Jiang Z, Wang Y, Li H*, Xiao A* (2020) N6-methyladenine in DNA antagonizes chromatin organizer SATB1 in early development. Nature 583: 625–630 Zhang M, Yang S, Nelakanti R, Zhao W, Liu G, Li Z, Liu X, Wu T, Xiao A*, and Li H* (2020) Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell Res 30: 197-210 Zheng Y, Zhang X, and Li H* (2020) Molecular basis for histidine N3-specific methylation of actin His73 by SETD3. Cell Disc 6, 3 Wang L, Gao Y, Zheng X, Liu C, Dong S, Li R, Zhang G, Wei Y, Qu H, Li Y, Allis CD, Li G, Li H*, and Li P* (2019) Histone modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism. Mol Cell 76: 646-659 Weinberg DN, Papillon-Cavanagh S, Chen H, Yue Y, Chen X, Rajagopalan KN, Horth C, McGuire JT, Xu X, Nikbakht H, Lemiesz AE, Marchione DM, Marunde MR, Meiners MJ, Cheek MA, Keogh MC, Bareke E, Djedid A, Harutyunyan AS, Jabado N, Garcia BA, Li H, Allis CD, Majewski J, and Lu C (2019) The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature 573: 281-286 Zhang X, Cao R, Niu J, Yang S, Ma H, Zhao S, and Li H* (2019) Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3. Cell Disc 5:35 Liu G, Zheng X, Guan H, Cao Y, Qu H, Kang J, Ren X, Lei J, Dong M, Li X, and Li H* (2019) Architecture of Saccharomyces cerevisiae SAGA complex. Cell Disc 5:25 Farrelly LA, Thompson RE, Zhao S, Lepack AE, Lyu Y, Bhanu NV, Zhang B, Loh YE, Ramakrishnan A, Vadodaria KC, Heard KJ, Erikson G, Nakadai T, Bastle RM, Lukasak BJ, Zebroski H 3rd, Alenina N, Bader M, Berton O, Roeder RG, Molina H, Gage FH, Shen L, Garcia BA, Li H, Muir TW, and Maze I* (2019) Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature 567: 535-539 Mariappan A, Soni K, Schorpp K, Zhao F, Minakar A, Zheng X, Mandad S, Macheleidt I, Ramani A, Kubelka T, Dawidowski M, Golfmann K, Wason A, Yang C, Simons, J, Schmalz, HG, Hyman AA, Aneja R, Ullrich R, Urlaub H, Odenthal M, Buttner R, Li H, Sattler M, Hadian K, and Gopalakrishnan J* (2019) Inhibition of CPAP–tubulin interaction prevents proliferation of centrosome-amplified cancer cells. EMBO J 38: e99876 Zhao S, Cheng L, Gao Y, Zhang B, Zheng X, Wang L, Li P*, Sun Q*, and Li H* (2019) Plant HP1 protein ADCP1 links multivalent H3K9 methylation readout to heterochromatin formation. Cell Res 29:54-66 Li X, Li XM, Jiang Y, Liu Z, Cui Y, Fung KY, van der Beelen She, Tian G, Wang L, Shi X, Allis CD, Li H, Li Y*, Li XD* (2018) Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking. Nat Chem Biol 14:1140-1149 Klein BJ, Vann KR, Andrews FH, Wang WW, Zhang J, Zhang Y, Beloglazkina AA, Mi W, Li Y, Li H, Shi X, Kutateladze AG, Strahl BD, Liu WR, and Kutateladze TG* (2018) Structural insights into the π-π-π stacking mechanism and DNA-binding activity of the YEATS domain. Nat Commun 9:4574 Fang J, Huang Y, Mao G, Yang S, Rennert G, Gu, L, Li H, and Li GM* (2018) Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3–MutSα interaction. Proc Natl Acad Sci USA 115: 9598-9603 Guo J, Zhao F, Yin W, Zhu M, Hao C, Pang Y, Wu T, Wang J, Zhao D*, Li H*, and Cheng M* (2018) Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors. Eur J Med Chem 155: 197-209 Hsu C, Zhao D, Shi J, Peng D, Guan H, Li Y, Huang Y, Wen H, Li W*, Li H*, and Shi X* (2018) Gas41 links histone acetylation to H2A.Z deposition and maintenance of embryonic stem cell identity. Cell Discovery 4(1), 28

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