何元政 - 哈尔滨工业大学

个人简介

工作经历 2017/12-迄今哈尔滨工业大学生命科学中心研究员 2014/01-2017/12 范安德研究所,密西根州研究助理教授 2008/09-2014/01 范安德研究所，密西根州研究科学家 2005/09-2008/09 美国国立卫生研究院，马里兰州研究学者 2000/10-2005/09 美国国立卫生研究院，马里兰州博士后教育经历 1995/09-2000/07 中科院上海生化所分子生物学博士 1991/09-1995/07 南京大学生理学本科

研究领域

主要研究兴趣是激素类受体，包括糖皮质类激素受体（Glucocorticoid Receptor）和G蛋白偶联受体（G-protein coupled receptors， GPCR）的结构，信号传导和相应的疾病药物开发。总体研究目标是利用各种结构生物学手段，包括是当前新兴的冷冻电镜技术，来解决信号传导上的关键机制，并转化成与疾病直接相关的治疗和药物开发，包括所谓的转化性研究（Translational Research）

近期论文

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Wang N, Qian Y, Xia R, Zhu X, Xiong Y, Zhang A, Guo C, He Y. Structural basis of CD97 activation and G-protein coupling. Cell Chem Biol. 2023 Aug 24;. doi: 10.1016/j.chembiol.2023.08.003. [Epub ahead of print] PubMed PMID: 37673067. 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 Aug;33(8):644-647. doi: 10.1038/s41422-023-00835-x. Epub 2023 Jun 7. PubMed PMID: 37286793; PubMed Central PMCID: PMC10397242. 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. 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 G(q), G(s), G(i), and G(12) coupling. Mol Cell. 2022 Nov 17;82(22):4340-4352.e6. doi: 10.1016/j.molcel.2022.10.009. Epub 2022 Oct 28. PubMed PMID: 36309016. 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. 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; PubMed Central PMCID: PMC8894450. 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. 2022 Mar;18(3):281-288. doi: 10.1038/s41589-021-00930-3. Epub 2021 Dec 22. PubMed PMID: 34937912. 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. PubMed PMID: 33828102; PubMed Central PMCID: PMC8027608. 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. 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. 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. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6932-6937. doi: 10.1073/pnas.1816734116. Epub 2019 Mar 20. PubMed PMID: 30894497; PubMed Central PMCID: PMC6452690. 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 Aug;560(7720):666-670. doi: 10.1038/s41586-018-0447-x. Epub 2018 Aug 22. PubMed PMID: 30135577. Liu H, Li J, Lu D, Li J, Liu M, He Y, Williams BO, Li J, Yang T. Ginkgolic acid, a sumoylation inhibitor, promotes adipocyte commitment but suppresses adipocyte terminal differentiation of mouse bone marrow stromal cells. Sci Rep. 2018 Feb 7;8(1):2545. doi: 10.1038/s41598-018-20244-0. PubMed PMID: 29416046; PubMed Central PMCID: PMC5803256. 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. PubMed PMID: 28753425; PubMed Central PMCID: PMC5567868. 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 Jun 16;292(24):9865-9881. doi: 10.1074/jbc.M117.782987. Epub 2017 Mar 29. PubMed PMID: 28356352; PubMed Central PMCID: PMC5473240. 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. Sci Adv. 2017 Jun;3(6):e1601217. doi: 10.1126/sciadv.1601217. eCollection 2017 Jun. PubMed PMID: 28630893; PubMed Central PMCID: PMC5457145. He Y, Gao X, Goswami D, Hou L, Pal K, Yin Y, Zhao G, Ernst OP, 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. Epub 2017 May 19. PubMed PMID: 28524165; PubMed Central PMCID: PMC5518878. Zhou XE, Gao X, Barty A, Kang Y, He Y, Liu W, Ishchenko A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Suino-Powell KM, Boutet S, Williams GJ, Wang M, Li D, Caffrey M, Chapman HN, Spence JC, Fromme P, Weierstall U, Stevens RC, Cherezov V, Melcher K, Xu HE. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex. Sci Data. 2016 Apr 12;3:160021. doi: 10.1038/sdata.2016.21. PubMed PMID: 27070998; PubMed Central PMCID: PMC4828943. Kang Y, Gao X, Zhou XE, He Y, Melcher K, Xu HE. A structural snapshot of the rhodopsin-arrestin complex. FEBS J. 2016 Mar;283(5):816-21. doi: 10.1111/febs.13561. Epub 2015 Nov 7. Review. PubMed PMID: 26467309; PubMed Central PMCID: PMC4783200. 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, Xu HE. Discovery of a highly potent glucocorticoid for asthma treatment. Cell Discov. 2015;1:15035-. doi: 10.1038/celldisc.2015.35. Epub 2015 Dec 15. PubMed PMID: 27066265; PubMed Central PMCID: PMC4822341. Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MH, Zhang C, Moeller A, West GM, Pascal BD, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad CE, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JC, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PubMed PMID: 26200343; PubMed Central PMCID: PMC4521999. 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. doi: 10.1101/gad.254904.114. PubMed PMID: 25691470; PubMed Central PMCID: PMC4335298. 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. doi: 10.1038/cr.2014.52. Epub 2014 Apr 25. PubMed PMID: 24763108; PubMed Central PMCID: PMC4042175. 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. doi: 10.1073/pnas.1322827111. Epub 2013 Dec 30. PubMed PMID: 24379397; PubMed Central PMCID: PMC3896210. Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H, Yuan Y, Yi W, Zhao L, Ma H, He Y, Wu Z, Melcher K, Qian Q, Xu HE, Wang Y, Li J. DWARF 53 acts as a repressor of strigolactone signalling in rice. Nature. 2013 Dec 19;504(7480):401-5. doi: 10.1038/nature12870. Epub 2013 Dec 11. PubMed PMID: 24336200; PubMed Central PMCID: PMC5802366. Lee GS, He Y, Dougherty EJ, Jimenez-Movilla M, Avella M, Grullon S, Sharlin DS, Guo C, Blackford JA Jr, Awasthi S, Zhang Z, Armstrong SP, London EC, Chen W, Dean J, Simons SS Jr. Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. J Biol Chem. 2013 May 24;288(21):15167-80. doi: 10.1074/jbc.M113.453936. Epub 2013 Apr 4. PubMed PMID: 23558686; PubMed Central PMCID: PMC3663537. Zhao LH, Zhou XE, Wu ZS, Yi W, Xu Y, Li S, Xu TH, Liu Y, Chen RZ, Kovach A, Kang Y, Hou L, He Y, Xie C, Song W, Zhong D, Xu Y, Wang Y, Li J, Zhang C, Melcher K, Xu HE. Crystal structures of two phytohormone signal-transducing α/β hydrolases: karrikin-signaling KAI2 and strigolactone-signaling DWARF14. Cell Res. 2013 Mar;23(3):436-9. doi: 10.1038/cr.2013.19. Epub 2013 Feb 5. PubMed PMID: 23381136; PubMed Central PMCID: PMC3587710. Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MH, Suino-Powell KM, He Y, Xu Y, Chalmers MJ, Brunzelle JS, Zhang H, Yang H, Jiang H, Li J, Yong EL, Cutler S, Zhu JK, Griffin PR, Melcher K, Xu HE. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science. 2012 Jan 6;335(6064):85-8. doi: 10.1126/science.1215106. Epub 2011 Nov 24. PubMed PMID: 22116026; PubMed Central PMCID: PMC3584687. Ai J, Tang Q, Wu Y, Xu Y, Feng T, Zhou R, Chen Y, Gao X, Zhu Q, Yue X, Pan Q, Xu S, Li J, Huang M, Daugherty-Holtrop J, He Y, Xu HE, Fan J, Ding J, Geng M. The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma. J Natl Cancer Inst. 2011 Nov 16;103(22):1696-712. doi: 10.1093/jnci/djr360. Epub 2011 Oct 24. PubMed PMID: 22025622; PubMed Central PMCID: PMC3216966. Guo Z, He Y, Wang S, Zhang A, Zhao P, Gao C, Cao B. Various effects of hepatoma-derived growth factor on cell growth, migration and invasion of breast cancer and prostate cancer cells. Oncol Rep. 2011 Aug;26(2):511-7. doi: 10.3892/or.2011.1295. Epub 2011 May 4. PubMed PMID: 21567096. 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. doi: 10.1126/scisignal.2001450. PubMed PMID: 21730326; PubMed Central PMCID: PMC3684214. He Y, Blackford JA Jr, Kohn EC, Simons SS Jr. STAMP alters the growth of transformed and ovarian cancer cells. BMC Cancer. 2010 Apr 7;10:128. doi: 10.1186/1471-2407-10-128. PubMed PMID: 20374646; PubMed Central PMCID: PMC2858746. Zhou XE, Suino-Powell KM, Li J, He Y, Mackeigan JP, Melcher K, Yong EL, Xu HE. Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J Biol Chem. 2010 Mar 19;285(12):9161-71. doi: 10.1074/jbc.M109.085779. Epub 2010 Jan 19. PubMed PMID: 20086010; PubMed Central PMCID: PMC2838335. Szapary D, Song LN, He Y, Simons SS Jr. Differential modulation of glucocorticoid and progesterone receptor transactivation. Mol Cell Endocrinol. 2008 Feb 13;283(1-2):114-26. doi: 10.1016/j.mce.2007.11.031. Epub 2007 Dec 8. PubMed PMID: 18215457; PubMed Central PMCID: PMC2275900. He Y, Simons SS Jr. STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repression. Mol Cell Biol. 2007 Feb;27(4):1467-85. doi: 10.1128/MCB.01360-06. Epub 2006 Nov 20. PubMed PMID: 17116691; PubMed Central PMCID: PMC1800712. Chen J, He Y, Simons SS Jr. Structure/activity relationships for GMEB-2: the second member of the glucocorticoid modulatory element-binding complex. Biochemistry. 2004 Jan 13;43(1):245-55. doi: 10.1021/bi035311b. PubMed PMID: 14705952. He Y, Szapary D, Simons SS Jr. Modulation of induction properties of glucocorticoid receptor-agonist and -antagonist complexes by coactivators involves binding to receptors but is independent of ability of coactivators to augment transactivation. J Biol Chem. 2002 Dec 20;277(51):49256-66. doi: 10.1074/jbc.M205536200. Epub 2002 Oct 9. PubMed PMID: 12376547.