Haitao LI,Ph.D.

Professor


1993-1997           Department of Microbiology, Shandong University      BSc

1997-2003           Institute of Biophysics, Chinese Academy of Sciences     PhD

2003-2010           Memorial Sloan-Kettering Cancer Center     Research Fellow (10/2003),

                  Research Associate (8/2005), and Senior Research Scientist (11/2006)

2010-2016           School of Medicine, Tsinghua University     Associate Professor

2016-present       School of Medicine, Tsinghua University     Professor

 

Research interest


My research is directed toward a molecular understanding of epigenetic regulation and modification biology. Epigenetics concerns the process that our genetic information is organized and decoded at the chromosomal level. Epigenetic mechanisms include chemical modifications to histones or DNA/RNA, histone variants, chromatin remodeling, and non-coding RNAs. Epigenetics plays a key role in many biological processes, ranging from gene regulation to cell fate decision.  Meanwhile, growing evidence shows that epigenetic dysregulation can give rise to diverse human diseases, notably cancer. We mainly apply structural biology blended with biochemical, chemical biological, and cell biological approaches to study key molecular recognition and catalysis events in epigenetics and modification biology. Other endeavors in the lab include structure-guided molecular engineering and drug discovery.


Selected publications


Keywords:

Epigenetics, Gene Regulation,  Modification Biology, Structure Biology, Cancer, Drug Discovery

Selected Publications (*correspondence):

Research Articles

1.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

2.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

3.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

4.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

5.Zhao S, Cheng L, Gao Y, Zhang B, Zheng X, Wang L, Li P*, Sun Q*, andLi H* (2018) Plant HP1 protein ADCP1 links multivalent H3K9 methylation readout to heterochromatin formation. Cell Res 0:1–13

6.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

7.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

8.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

9.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

10.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

11.Cao R, Zhang X, Liu X, Li Y, and Li H* (2018) Molecular basis for histidine N1 position-specific methylation by CARNMT1. Cell Res 28: 494-496

12.Hsu C, Shi J, Yuan C, Zhao D, Jiang S, Lyu J, Wang X, Li H, Wen H, Li W, and Shi X (2018) Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer. Genes Dev, 32: 58-69

13.Zhao S, Zhang B, Yang M, Zhu J, and Li H* (2018) Systematic profiling of histone readers in Arabidopsis thaliana. Cell Reports 22: 1090-1102

14.Hao C, Zhao F, Song HY, Guo J, Li X, Jiang X, Huang R, Song S, Zhang Q, Wang R, Wang K, Pang Y, Liu T, Lu T, Huang W, Wang J, Lin B, He Z, Li H* , Li F*, Zhao D*, and Cheng M* (2018) Structure-based design of 6-chloro-4-aminoquinazoline-2-carboxamide derivatives as potent and selective p21-activated kinase 4 (PAK4) inhibitors. J Med Chem 61: 265-285

15.Mi W, Guan H, Lyu J, Zhao D, Xi Y, Jiang S, Andrews FH, Wang X, Gagea M, Wen H, Tora L, Dent SYR, Kutateladze TG, Li W*, Li H* , and Shi X* (2017) YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer. Nat Commun 8:1088

16.Li Z, Zhao D, Xiang B, and Li H* (2017) Structural and biochemical characterization of DAXX-ATRX interaction. Protein Cell  8: 762-766

17.Zhao S, Yang M, Zhou W, Zhang B, Cheng Z, Huang J. Zhang M, Wang Z, Wang R, Chen Z, Zhu J*, and Li H* (2017) Kinetic and high-throughput profiling of epigenetic interactions by 3D-carbene chip-based surface plasmon resonance imaging technology. Proc Natl Acad Sci USA 114: E7245-E7254

18.Bae N, Viviano M, Su X, Lyu J, Cheng D, Sagum C, Castellano S, Bai X, Johnson C, Khalil ML, Shen J, Chen K, Li H* , Sbardella G*, and Bedford MT* (2017) Developing Spindlin1 small molecule inhibitors using protein microarrays. Nat Chem Biol 13:750-756

19.Wan L, Wen H, Li Y, Lvu J, Xi Y, Hoshii T, Joseph J, Wang X, Loh Y, Erb MA, Souza AL, Bradner JE, Shen L, Li W, Li H#, Allis CD#*, Armstrong SA#*, and Shi X#* (2017) ENL links histone acetylation to oncogenic gene expression in AML. Nature 543, 265-269 ( #co-senior author)

20.Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, and Li H* (2016) Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2. Nat Chem Biol 12:1111-1118

21.Yang S, Zheng X, Lu C, Li G-M, Allis CD, and Li H* (2016) Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase. Genes Dev 30:1611-1616

22.Li N, Li Y, Chen K, Zheng X, Shen H, Wen H, Chen T. Dhar SS, Kan P, Zhu G, Wang Z, Shi X, Lan F, Li W*, Li H* and Lee MG* (2016) ZMYND8 complexes with JARID1D to read a poised histone H3K4me1-H3K14ac signature for metastasis-linked gene repression. Mol Cell 63:470-484

23.Zheng X, Ramani A, Soni K, Gottardo M, Zheng S, Ming Gooi L, Li W, Feng S, Mariappan A, Wason A, Wildlund P, Pozniakovaky A, Poser I, Deng H, Ou G, Riparbelli MG, Callaini G, Sattler M, Hyman A, Gopalakrishnan J*, Li H* (2016) Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length. Nat Commun 7:11874

24.Zhang X, Zhao D, Xiong X, He Z, and Li H*(2016) Multifaceted histone H3 methylation and phosphorylation readout by the plant homeodomain (PHD) finger of human nuclear antigen Sp100C. J Biol Chem 291:12786-12798

25.Zhao D, Guan H, Zhao S, Mi W, Wen H, Li Y, Zhao Y, Allis CD, Shi X*, and Li H*(2016) YEATS2 is a selective histone crotonylation reader. Cell Research 26:629–632

26.Li Y, Sabari BR, Panchenko T, Wen H, Zhao D, Guan H, Wan L, Tang Z, Zhao Y, Roeder R. Shi X, Allis CD*, and Li H* (2016) Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain. Mol Cell 62:181-193

27.Zhao D, Zhang X, Guan H, Xiong X, Shi Xi, Deng H, and Li H* (2016) The BAH domain of BAHD1 is a histone H3K27me3 reader. Protein Cell  7: 222-226

28.Wu R, Yue Y, Zheng X, and Li H* (2015) Molecular basis for histone N-terminal methylation by NRMT1. Genes Dev 29:2337-2342

29.Kamps J, Huang J, Poater J, Xu C, Pieters B, Dong A, Min J, Sherman W, Beuming T, Bickelhaupt FM, Li H, and Mecinovic J* (2015) Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins. Nat Commun 6: 8911

30.Noh K, Wang H, Kim HR, Wenderski W, Fang F, Li CH, Dewell S, Hughes SH, Melnick AM, Patel DJ, Li H* , and Allis CD* (2015) Engineering of a histone-recognition domain in Dntm3a alters the epigenetic landscape and phenotypic features of mouse ESCs. Mol Cell 59:89-103

31.Noh K, Maze I, Zhao D, Xiang B, Wenderski W, Lewis PW, Shen L, Li H* and Allis CD* (2015) ATRX tolerates activity-dependent histone H3 "methyl/phos switching" to maintain repetitive element silencing in neurons. Proc Natl Acad Sci USA 112(22): 6820-6827

32.Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SYR, Li W, Li H*, and Shi X* (2014) AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation. Cell 159:558-571

33.Wen H*, Li, Y, Xi Y, Jiang S, Stratton S, Peng D, Tanaka K, Ren Y, Xia Z, Wu J, Li B, Barton MC, Li W*, Li H* , and Shi X* (2014) ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature 507, 263-268

34.Su X, Zhu G, Ding X, Lee SY, Dou Y, Zhu B, Wu W*, and Li H* (2014) Molecular basis underlying histone H3 lysine-arginine methylation patter readout by Spin/Ssty repeats of Spindlin1. Genes Dev 28:622-636

35.Zheng X, Gooi, LM, Wason A, Gabriel E, Mehrjardi NZ, Yang Q, Zhang X, Debec A, Basiri M, Avidor-Reiss T, Pozniakovsky A, Poser I, Saric T, Hyman AA, Li H* and Gopalakrishnan J* (2014) The conserved TCP domain of Sas-4/CPAP is essential for Peri-centriolar material tethering during centrosome biogenesis. Proc Natl Acad Sci USA 111: E345-E363

36.Ratnakumar K, Duarte LF, LeRoy G, Hasson D, Smeets D, Vardabasso C, B?nisch C, Zeng T, Xiang B, Zhang DY, Li H, Wang X, Hake SB, Schermelleh L, Garcia BA, Bernstein E (2012) ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha globin expression. Gene & Dev 26(5): 433-438

37.Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ*, Li H*, Shi Y* (2011) ATRX links atypical histone methylation recognition mechanisms to human mental retardation syndrome. Nat Struct Mol Biol 18: 769-776

38.Ruthenburg AJ,Li H, Milne T, Dou Y, McGinty RK, Yuen M, Muir TW, Patel DJ and Allis CD (2011) Recognition of a Mononucleosomal Histone Modification Pattern by BPTF via Multivalent Interactions. Cell 145: 692-706

39.Wang Z, Song J, Tom M, Wang GG, Li H, Allis CD and Patel DJ (2010) Pro Isomerization in MLL1 PHD3-Bromo Cassette Connects H3K4me Readout to CyP33 and HDAC-Mediated Repression. Cell 141:1183-94

40.Xiao A,Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ and Allis CD. (2009) WSTF regulates the DNA damage response of H2A.X via a novel tyrosine kinase activity. Nature 457, 57-62

41.Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H, Luo J, Patel DJ and Allis CD (2009) Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459, 847-851

42.Wang Y, Juranek S, Li H, Sheng G, Greg SW, Tuschl T and Patel DJ (2009) Nucleation, propagation and cleavage of target RNAs in argonaute silencing complexes. Nature 461:754-61

43.Li H#, Motamedi MR#, Yip CK, Wang Z, Walz T, Patel DJ and Moazed D (2009) An alpha motif at Tas3 C terminus mediates RITS cis-spreading and promotes heterochromatic gene silencing. Mol Cell 34(2), 155-167 (#equal contribution)

44.Wang Y, Juranek S, Li H, Sheng G, Tuschl T and Patel DJ (2008) Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921-926

45.Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, and Patel DJ (2007) Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell 28, 677-691

46.Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis, CD, and Patel DJ (2006) Molecular basis for site-specific readout of histone H3K4 trimethylation by the BPTF PHD finger of NURF. Nature 442, 91-95

Invited Reviews & Book Chapters

1.Zhao S, Yue Y, Li Y and Li H* (2019) Identification and characterization of ‘readers’ for novel histone modifications. Curr Opin Chem Biol, 51:57-65

2.Zhao S, Zhang X, and Li H* (2018) Beyond histone acetylation – writing and erasing histone acylations Curr Opin Struc Biol, 53:169–177

3.Zhao S, Li Y, and Li H* (2018) Chemical and biological foundations of histone modification. In: Zhu JD (eds) Epigenetics and Precision Medicine:132-157 Shanghai Jiaotong University Press (Chapter 5, in Chinese, ISBN 9787313184115)

4.Zhao D, Li Y, Xiong X, Chen Z, and Li H* (2017) YEATS domain - a histone acylation reader in health and disease. J Mol Biol, 429:1994-2002

5.Li Y, Zhao D, Chen Z, and Li H* (2017) YEATS domain: Linking histone crotonylation to gene regulation. Transcription, 8, 9-14

6.Noh K, Allis CD*, and Li H* (2016) Reading between the lines: “ADD”-ing histone and DNA methylation marks towards a new epigenetic “sum”. ACS Chem Biol 11:554-563

7.Zhao S and Li H* (2015) Crystallography-based mechanistic insights into epigenetic regulation. Elsevier Publisher- Y. G. Zheng (ed.) Epigenetic Technological Applications:125-147

8.Li H* , Zhao S, and Patel DJ (2015) Histone recognition by tandem modules and modulation by multiple PTMs. Springer Books - Life Sciences and Biomedicine, M.-M. Zhou (ed.) Histone Recognition:149-172

9.Zhao S, Su X, Li Y, and Li H* (2015) Research advances in the mechanism of histone methylation recognition by reader modules. Science & Technology Review, 33(8): 94-100  (in Chinese)

10.Wee S, Dhanak D, Li H, Armstrong SA, Copeland RA, Sims R, Goodman VL, Baylin SB, Liu XS, Tarakhovsky A, and Schweizer L* (2014) Targeting epigenetic regulators for cancer therapy. Ann NY Acad Sci 1309:30-36

11.Li Y and Li H* (2012) Many keys to push: diversifying the ‘readership’ of plant homeodomain fingers. Acta Biochim Biophys Sin 44 (1): 28-39

12.Li H# , Taverna SD#, Ruthenburg AJ#, Patel DJ, and Allis CD (2007) Readout of chromatin marks by histone-binding modules. Nat Rev Mol Cell Biol 8(12) (#equal contribution) (Poster) (http://www.nature.com/nrm/posters/histonemarks/histonemarks.pdf)

13.Ruthenburg AJ, Li H, Patel DJ, and Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983-994

14.Taverna SD*#,Li H*# , Ruthenburg AJ, Allis CD, and Patel DJ* (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14(11):1025-1040  (#equal contribution & *correspondence)

Awards


  • 2019 Young Scholar of China Award in Cancer Research

  • 2019 Promega Innovation Awards for Cell Biology

  • 2016 The 15th Outstanding Mentor Award, Tsinghua University

  • 2015 The 9th Annual Wuxi PharmaTech Life Science and Chemistry Awards

  • 2015 HFSP Young Investigators Grant Award

  • 2014 The 17th Mao Yi-sheng Science and Technology Award for Beijing Youth

  • 2013 Tsinghua Young Scholar of Distinction

  • 2012 MOE New Century Excellent Talents in University


 

Editorial Board:

2018-present Transcription

2018-present Clinical Epigenetics

2015-present Signal Transduction and Targeted Therapy


Contact information


Email: lht at tsinghua.edu.cn

Phone: +86-10-62771392 (office)

              +86-10-62796944 (lab)

Address: Medical Science Building, Rms C228 (office) C224/C225 (lab), Tsinghua University, Beijing 100084

Webpage: https://www.scopus.com/authid/detail.uri?authorId=39861627900