Wenshe Liu, PhD

Education and Training

• Peking University, B.S., 2000
• UC-Davis, PhD, 2005
• Scripps Research Institute, Postdoc, 2005-2007

Research Interests

My laboratory is interested in the understanding of the epigenetic chromatin regulation by posttranslational histone modifications and the development of therapeutics that target chromatin epigenetics. The laboratory has two functional units: the biological unit and the chemical unit. In the four core histones of human chromatin exist a large variety of posttranslational modifications. These modifications regulate functions of chromatin by influencing its structure and interactions with transcriptional factors. To study regulatory roles of these posttranslational modifications in chromatin, the biological unit in the laboratory has been developing methods that combine both molecular biology and chemical biology to assemble chromatin with posttranslational modifications for cryo-EM structural studies and biochemical analysis of their interactions with epigenetic proteins. Active projects include chromatin dynamics influenced by lysine acetylation and lysine methylation, sirtuin and HDAC interactions with acetylated chromatin, LSD1-2 interactions with methylated chromatin, and histone acetyltransferase-catalyzed chromatin acetylation based on proteomic analysis. Since most epigenetic proteins including sirtuins, HDACs, histone demethylases, histone acetyltransferases, histone methyltransferases, and reader proteins for chromatin modifications are related to disease development in humans, the chemical unit in the laboratory is developing therapeutics that targeting these proteins for disease intervention. Approaches we have been employed include novel phage display techniques that have been developed in the laboratory and also small molecule synthesis that most researchers are using. Therapeutic targets we are actively pursue inhibitors for include SIRT1-3, HDAC1-11, LSD1-2, ENL, and BRD9.

Awards, Recognition and Service

• Presidential Impact Fellow, 2018
• Gradipore Endowed Chair in Chemistry, 2018
• ACS Chemical Biology Most Prolific Author, 2017
• CAPA Distinguished Professor Award, 2016
• Emile and Marta Schweikert Endowed Professorship, 2014
• NSF Career Award, 2012
• Molecular BioSystems Emerging Investigator, 2010

Representative Publications

1. Klein BJ, Jang SM, Lachance C, Mi W, Lyu J, Sakuraba S, Krajewski K, Wang WW, Sidoli S, Liu J, Zhang Y, Wang X, Warfield BM, Kueh AJ, Voss AK, Thomas T, Garcia BA, Liu WR, Strahl BD, Kono H, Li W, Shi X, Côté J, Kutateladze TG. Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation. Nat Commun. 2019 Oct 17;10(1):4724. doi: 10.1038/s41467-019-12551-5. PubMed PMID: 31624313; PubMed Central PMCID: PMC6797804.

2. Wang XS, Chen PC, Hampton JT, Tharp JM, Reed CA, Das SK, Wang DS, Hayatshahi HS, Shen Y, Liu J, Liu WR. A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library. Angew Chem Int Ed Engl. 2019 Oct 28;58(44):15904-15909. doi: 10.1002/anie.201908713. Epub 2019 Sep 9. Review. PubMed PMID: 31398275; PubMedCentral PMCID: PMC6803038.

3. Ghosh AK, Samanta I, Mondal A, Liu WR. Covalent Inhibition in Drug Discovery. ChemMedChem. 2019 May 6;14(9):889-906. doi: 10.1002/cmdc.201900107. Epub 2019 Mar 1. Review. PubMed PMID: 30816012; PubMed Central PMCID: PMC6816337.

4. Wang WW, Angulo-Ibanez M, Lyu J, Kurra Y, Tong Z, Wu B, Zhang L, Sharma V, Zhou J, Lin H, Gao YQ, Li W, Chua KF, Liu WR. A Click Chemistry Approach Reveals the Chromatin-Dependent Histone H3K36 Deacylase Nature of SIRT7. J Am Chem Soc. 2019 Feb 13;141(6):2462-2473. doi: 10.1021/jacs.8b12083. Epub 2019 Feb 4. PubMed PMID: 30653310; PubMed Central PMCID: PMC6812484.

5. Yan H, Yang W, Zhou F, Li X, Pan Q, Shen Z, Han G, Newell-Fugate A, Tian Y, Majeti R, Liu W, Xu Y, Wu C, Allred K, Allred C, Sun Y, Guo S. Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes. 2019 Feb;68(2):291-304. doi: 10.2337/db18-0638. Epub 2018 Nov 28. PubMed PMID: 30487265; PubMed Central PMCID: PMC6341301.

6. 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, Kutateladze TG. Structural insights into the π-π-π stacking mechanism and DNA-binding activity of the YEATS domain. Nat Commun. 2018 Nov 1;9(1):4574. doi: 10.1038/s***************-6. PubMed PMID: 30385749; PubMed Central PMCID: PMC6212594.

7. Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Schölz C, Hamilton WB, Zucconi BE, Wang WW, Liu WR, Brickman JM, Kesicki EA, Lai A, Bromberg KD, Cole PA, Choudhary C. Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. Cell. 2018 Jun 28;174(1):231-244.e12. doi: 10.1016/j.cell.2018.04.033. Epub 2018 May 24. PubMed PMID: 29804834; PubMed Central PMCID: PMC6078418.

8. Kakkar N, Perez JG, Liu WR, Jewett MC, van der Donk WA. Incorporation of Nonproteinogenic Amino Acids in Class I and II Lantibiotics. ACS Chem Biol. 2018 Apr 20;13(4):951-957. doi: 10.1021/acschembio.7b01024. Epub 2018 Feb 21. PubMed PMID: 29439566; PubMed Central PMCID: PMC5910287.

9. Tharp JM, Liu WR. Using Amber and Ochre Nonsense Codons to Code Two Different Noncanonical Amino Acids in One Protein Gene. Methods Mol Biol. 2018;1728:147-154. doi: 10.1007/978-1-4939-7574-7_9. PubMed PMID: 29404996.

10. Huang J, Mousley CJ, Dacquay L, Maitra N, Drin G, He C, Ridgway ND, Tripathi A, Kennedy M, Kennedy BK, Liu W, Baetz K, Polymenis M, Bankaitis VA. A Lipid Transfer Protein Signaling Axis Exerts Dual Control of Cell-Cycle and Membrane Trafficking Systems. Dev Cell. 2018 Feb 5;44(3):378-391.e5. doi: 10.1016/j.devcel.2017.12.026. Epub 2018 Jan 27. PubMed PMID: 29396115; PubMed Central PMCID: PMC6444186.