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Yuanzheng He
Publisher:张宁  Time2017-09-14 View:1198


Yuanzheng He

Phone: 86-451-86402026
Research Area:  Receptor (GPCRs and   nuclear receptors) signaling, structure and  drug discovery

After  graduating from the Chinese Academy of Sciences’ Shanghai Institute of  Biochemistry in 2000, Dr. He worked as a postdoctoral fellow at the National  Institute of Diabetes and Digestive and Kidney Diseases at the National  Institutes of Health in Maryland. While there, he studied the mechanism of  steroid hormone receptor-regulated gene expression, specifically the  glucocorticoid receptor (GR). In 2008, Dr. He was recruited to Van Andel  Research Institute to work on drug discovery for the glucocorticoid receptor and  structural basis of G-coupled protein receptors (GPCRs) signaling. In 2014, Dr.  He became a research assistant professor at Van Andel Research Institute. During  this period, Dr. He discovered a crosstalk between lysosomal pathway and  glucocorticoid signaling, designed and developed novel glucocorticoids for  asthma treatment, made major contribution to the rhodopsin/arrestin complex  structure, and identified key mechanism for rhodopsin/GRK1 engagement. Dr. He  joins the School of Life Sciences and Technology of the Harbin Institute of  Technology in November 2017.


Research Interests

Dr.  He’s research interests are hormone receptor signaling and the related  translational studies, focusing on steroid hormone receptors (i.e. the  glucocorticoid receptor, GR) and the G-protein coupled receptors (GPCRs). The  overall research goal of Dr. He is to use cutting edge structural biology tools,  including the emerging cryo-electron microscopy (EM), to explore the molecular  detail, including those at the atomic level, of receptor signaling and use it to  design precision medicines that specifically deliver the desired treatment  effects, but not the unwanted side effects, to  patients.

Techniques and Tools in the Lab

      Protein expression and purification, protein crystallization, structure  determination,Cryo-EM,  small molecule design, animal model of inflammatory diseases, molecular biology  and cellular biology techniques

Selected Publications

Dr.  He has published more than 30 peer review papers, including Cell, Nature, Science, Molecular Cell, Nature Chemical Biology, Nature Communications, Cell Research, PNAS, Genes & Development, Science Signaling. Below  is selected publication of Dr. He.

Since December of 2017

1. Yin H, Inoue A, Ma Z, Zhu X, Xia R, Xu Z, Wang N, Duan Y, Zhang A, Guo C, He Y#. Structural basis of omega-3 fatty acid receptor FFAR4 activation and G protein coupling selectivity. Cell Res. 2023 Jun 7;. doi: 10.1038/s41422-023-00835-x. [Epub ahead of print] PubMed PMID: 37286793.

2. Liang J*, Inoue A*#, Ikuta T, Xia R, Wang N, Kawakami K, Xu Z, Qian Y, Zhu X, Zhang A, Guo C, Huang Z, He Y#. Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation. Nat Commun. 2023 Feb 23;14(1):1012. doi: 10.1038/s41467-023-36575-0. PubMed PMID: 36823105; PubMed Central PMCID: PMC9950150.

3. Qian Y, Ma Z, Liu C, Li X, Zhu X, Wang N, Xu Z, Xia R, Liang J, Duan Y, Yin H, Xiong Y, Zhang A, Guo C, Chen Z, Huang Z, He Y#. Structural insights into adhesion GPCR ADGRL3 activation and Gq, Gs, Gi, and G12 coupling. Mol Cell. 2022 Oct 28;. doi: 10.1016/j.molcel.2022.10.009. [Epub ahead of print] PubMed PMID: 36309016.

4. Zhu X, Qian Y, Li X, Xu Z, Xia R, Wang N, Liang J, Yin H, Zhang A, Guo C, Wang G, He Y#. Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling. Nat Commun. 2022 Sep 20;13(1):5513. doi: 10.1038/s41467-022-33173-4. PubMed PMID: 36127364; PubMed Central PMCID: PMC9489763.

5. Wang N, He X, Zhao J, Jiang H, Cheng X, Xia Y, Eric Xu H, He Y#. Structural basis of leukotriene B4 receptor 1 activation. Nat Commun. 2022 Mar 3;13(1):1156. doi: 10.1038/s41467-022-28820-9. PubMed PMID: 35241677.

6. Xu Z*, Ikuta T*, Kawakami K, Kise R, Qian Y, Xia R, Sun MX, Zhang A, Guo C, Cai XH, Huang Z, Inoue A#, He Y#. Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism. Nat Chem Biol. 2021 Dec 22;. doi: 10.1038/s41589-021-00930-3. [Epub ahead of print] PubMed PMID: 34937912.

7. Xia R*, Wang N*, Xu Z*, Lu Y, Song J, Zhang A, Guo C, He Y#. Cryo-EM structure of the human histamine H 1 receptor/G q complex. Nat Commun. 2021 Apr 7;12(1):2086. doi: 10.1038/s41467-021-22427-2.

8. Lu Y*, Zhou XE*, Gao X, Wang N, Xia R, Xu Z, Leng Y, Shi Y, Wang G, Melcher K, Xu HE, He Y#. Crystal structure of heliorhodopsin 48C12. Cell Res. 2020 Jan;30(1):88-90. doi: 10.1038/s41422-019-0266-0. Epub 2019 Dec 26. PubMed PMID: 31879417; PubMed Central PMCID: PMC6951262.

9. Yin W, Li Z, Jin M, Yin YL, de Waal PW, Pal K, Yin Y, Gao X, He Y, Gao J, Wang X, Zhang Y, Zhou H, Melcher K, Jiang Y, Cong Y, Edward Zhou X, Yu X, Eric Xu H. A complex structure of arrestin-2 bound to a G protein-coupled receptor. Cell Res. 2019 Dec;29(12):971-983. doi: 10.1038/s41422-019-0256-2. Epub 2019 Nov 27. PubMed PMID: 31776446; PubMed Central PMCID: PMC6951264..

10. He Y *#, Shi J*, Nguyen QT*, You E, Liu H, Ren X, Wu Z, Li J, Qiu W, Khoo SK, Yang T, Yi W, Sun F, Xi Z, Huang X, Melcher K, Min B#, Xu HE#. Development of highly potent glucocorticoids for steroid-resistant severe asthma. PNAS2019; 116(14):6932-6937.*, contribute equally.#, corresponding author.

11. Yang S, Wu Y, Xu TH, de Waal PW, He Y, Pu M, Chen Y, DeBruine ZJ, Zhang B, Zaidi SA, Popov P, Guo Y, Han GW, Lu Y, Suino-Powell K, Dong S, Harikumar KG, Miller LJ, Katritch V, Xu HE, Shui W, Stevens RC, Melcher K, Zhao S, Xu F. Crystal structure of the Frizzled 4 receptor in a ligand-free state. Nature. 2018; 560(7720):666-670.


Befor December of 2017

12. Zhou XE*, He Y*, de Waal PW*, Gao X*, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell, 2017 Jul 27;170(3):457-469.e13. doi: 10.1016/j.cell.2017.07.002. Cover article of Cell v170.

13. He Y#, Gao X, Goswami D Hou L, Pal K, Yin Y, Zhao G, Ernst O.P, Griffin P, Melcher K, Xu HE#. Molecular Assembly of Rhodopsin with G-Protein Coupled Receptor Kinases. Cell Res. 2017 Jun;27(6):728-747. doi: 10.1038/cr.2017.72.

14. Yin Y, de Waal PW, He Y, Zhao LH, Yang D, Cai X, Jiang Y, Melcher K, Wang MW, Xu HE. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors. J Biol Chem. 2017; 292(24):9865-9881.

15. Ma H, Duan J, Ke J, He Y, Gu X, Xu TH, Yu H, Wang Y, Brunzelle JS, Jiang Y, Rothbart SB, Xu HE, Li J, Melcher K. A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex. Science advances. 2017; 3(6):e1601217.

16. Kang Y*, Zhou XE*, Gao X*, He Y*,Liu W, Ishchenko A, …Stevens RC, Cherezov V, Melcher K, Xu HE. Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7.

17. He Y#,Shi J, Yi W, Ren X, Gao X, Li J, Wu N, Weaver K, Xie Q, Khoo SK, Yang T, Huang X, Melcher K and Xu HE#. Discovery of a highly potent glucocorticoid for asthma treatment. Cell Disc 2015, 1. pii: 15035.

18. Zhi X, Zhou XE, He Y, Searose-Xu K, Zhang CL, Tsai CC, Melcher K, Xu HE. Structural basis for corepressor assembly by the orphan nuclear receptor TLX. Genes Dev. 2015 Feb 15;29(4):440-50.

19. He Y#,Yi W, Suino-Powell K, Zhou XE, Tolbert WD, Tang X, Yang J, Yang H, Shi J, Hou L, Jiang H, Melcher K, Xu HE#. Structures and mechanism for the design of highly potent glucocorticoids. Cell Res. 2014 Jun;24(6):713-26.

20. Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, Melcher K, Mangelsdorf DJ, Xu HE. Structural insights into gene repression by the orphan nuclear receptor SHP. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):839-44.

21. Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, He Y. et al. DWARF 53 acts as a repressor of strigolactone signaling in rice. Nature, 2013, 504: 401-405.

22. Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MHE, Suino-Power KM, He Y, Xu Y, .Mecher K, Xu HE. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science. 2012 Jan 6;335(6064):85-8.

23. He Y#, Xu Y, Zhang C, Gao X, Dykema KJ, Martin KR, Ke J, Hudson EA, Khoo SK, Resau JH, Alberts AS, MacKeigan JP, Furge KA, Xu HE#. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal. 2011 Jul 5;4(180):ra44. Cover article.


Dr. He’s complete list of publications: