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个人简介

教育背景 1999.9-2003.7,山东大学生命科学学院,生物技术 学士 2003.9-2008.7,中科院上海药物研究所,药物设计 博士 工作经历 2008.8-2011.7,美国加州大学戴维斯分校,博士后 2011.8-2016.8,美国桑福德伯纳姆医学研究所,博士后 2016.9-至今,山东大学微生物技术国家重点实验室,教授

研究领域

分子药理学、结构生物学、化学生物学 本课题组专注于研究重大疾病相关的靶标蛋白。目前重点研究“类核受体”转录因子——bHLH-PAS(basic helix-loop-helix-PER-ARNT-SIM)家族,它们与很多人类疾病密切相关,而且普遍含有小分子配体结合口袋,因此是继核受体之后第二个可作为潜在药物靶标的转录因子家族。一方面综合利用多种实验方法,研究这些蛋白的结构和功能,并揭示蛋白和配体的相互作用,以及配体调控蛋白活性的分子机理;另一方面通过设计和搭建多种化合物筛选体系,发现新的靶向小分子,并进一步通过计算模拟和结构改造等手段,获得活性更好的新药先导化合物。

近期论文

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Song W, Zhuang J, Zhang N, Ren X, Xu W, Guo M, Diao X, Liu C, Jin J,Wu D*, Zhang Y*.SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production.Bioorg Med Chem. 2023, 77: 117041.(*共同通讯作者) Sun X, Jing L, Li F, Zhang M, Diao X, Zhuang J, Rastinejad F,Wu D. Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proc Natl Acad Sci USA. 2022, 119: e2208804119.(独立通讯作者) Ren X, Diao X, Zhuang J*,Wu D*. Structural basis for the allosteric inhibition of hypoxia-inducible factor 2 by belzutifan.Mol Pharmacol.2022, 102: 240-247.(*共同通讯作者) Diao X, Ye F, Zhang M, Ren X, Tian X, Lu J, Sun X, Hou Z, Chen X, Li F, Zhuang J, Ding H, Peng C, Rastinejad F*, Luo C*,Wu D*. Identification of oleoylethanolamide as an endogenous ligand for HIF-3α.Nat Commun.2022, 13: 2529.(*共同通讯作者) Zhuang J, Liu Q,Wu D*, Tie L*. Current strategies and progress for targeting the "undruggable" transcription factors.Acta Pharmacol Sin. 2022, 43: 2474-2481.(*共同通讯作者) Li F, Song C, Zhang Y,Wu D. Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs.Acta Biochim Biophys Sin (Shanghai). 2022, 54: 12-24.(独立通讯作者)[封面文章] Wu D*, Su X, Lu J, Li S, Hood BL, Vasile S, Potluri N, Diao X, Kim Y, Khorasanizadeh S, Rastinejad F*. Bidirectional modulation of HIF-2 activity through chemical ligands.Nat Chem Biol.2019, 15: 367-376. (*共同通讯作者)[获得F1000Prime推荐] Chandra V#,Wu D#, Li S, Potluri N, Kim Y, Rastinejad F. The quaternary architecture of RARβ-RXRα heterodimer facilitates domain-domain signal transmission.Nat Commun.2017, 8: 868.(#共同第一作者) Wu D, Rastinejad F. Structural characterization of mammalian bHLH-PAS transcription factors.Curr Opin Struct Biol.2017, 43: 1-9. Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D, Rajpal DK, Creech K, Furst S, Lee J,Wu D, Rastinejad F, Willson TM, Viviani F, Morris DC, Moore JT, Cote-Sierra J. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans.J Invest Dermatol.2017, 137: 2110-2119. Wu D, Su X, Potluri N, Kim Y, Rastinejad F. NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.eLife.2016, 5: e18790. Wu D, Potluri N, Lu J, Kim Y, Rastinejad F. Structural integration in hypoxia-inducible factors.Nature.2015, 524: 303-308. [在Nature同期News&Views栏目中被特别介绍,并获得F1000Prime推荐] Wu D, Potluri N, Kim Y, Rastinejad F. Structure and dimerization properties of the aryl hydrocarbon receptor PAS-A domain.Mol Cell Biol.2013, 33: 4346-4356. [被编辑选为当期“意义显著”论文之一] Wu D#, Nishimura N#, Kuo V, Fiehn O, Shahbaz S, Van Winkle L, Matsumura F, Vogel CF. Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice.Arterioscler Thromb Vasc Biol.2011, 31: 1260-1267. (#共同第一作者)[被编辑在同期社论中推荐]

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