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夏青

教授、博士生导师

夏青  长聘教授 医学博士

E-mail: xqing@hsc.pku.edu.cn

 

研究领域前沿生物技术及再生医学

 

个人简介

2004年获北京大学医学博士,2004-2006无机化学博士后,2010-2011南加州大学药学院,2014-2015哈佛医学院。截至2022年,发表SCI论文50篇,申请国际国内专利19项。已结题两项科技部重大新药创制项目,参与多项国家重大研究计划。参编国家十三药理学教材,参与讲授《细胞与分子生物学》、《细胞工程与治疗》、《前沿生物技术》本科课程。

 

学术成果与研究方向

单基因病治疗,合成生物学,化学生物学

将核酸信息解码成蛋白序列是中心法则的重要组成部分,完成这一过程需要蛋白质翻译机器的精确运行。夏青实验室致力于从遗传信息中心法则出发,利用生物学、化学合成等多学科手段制作新型基因解码器,在翻译过程中实现精准的蛋白质编辑。至今,夏青实验室已初步实现利用新型蛋白质翻译机器对无义突变类型单基因病的治疗性验证,开发了非天然碱基、非天然氨基酸系统、“tRNA-正交系统,以及酶定向进化等技术,目前着力从头设计翻译机器的各个元件以实现提高解码效率和控制蛋白质翻译速度,并尝试进一步拓展新型基因解码器对单基因病的治疗应用。

 

Papers (*corresponding author)  

1.  Zheng ZT, Shi NN, Xia Q*. AAV-delivered engineered tRNA-enzyme pairs suppress nonsense mutation in mice. STAR Protoc, 2022 Accepted.

2.  Wu XS, Zheng ZT, Chen HM, Lin HS, Yang YL, Xia Q*. Sterilization of Drug-Resistant Influenza Virus through Genetic Interference Inspired by Unnatural Amino Acid-Engineered Particles. Adv Therapeut, 2022 Oct 25, 5 (10).

3.  Shi NN, Tong L, Lin HS, Zheng ZT, Zhang HR , Dong LZ, Yang YL, Shen YX, Xia Q*. Optimizing eRF1 to Enable the Genetic Encoding of Three Distinct Noncanonical Amino Acids in Mammalian Cells. Adv Biol (Weinh). 2022 Jul 11; e2200092.

4.  Zhang H, Zheng Z, Dong L, Shi N, Yang Y, Chen H, Shen Y, Xia Q*. Rational incorporation of any unnatural amino acid into proteins by machine learning on existing experimental proofs.Comput Struct Biotechnol J. 2022 Sep 5;20:4930-4941.

5.  Zhang X, Lin H, Dong L, Xia Q*. Recapitulating influenza virus infection and facilitating antiviral and neuroprotective screening in tractable brain organoids.Theranostics. 2022 Jul 7;12(12):5317-5329.

6.  Jiang Z, Lin H, Zhang H, Shi N, Zheng Z, Dong L, Yang Y, Xia Q*. An Integrative Analysis of the Immune Features of Inactivated SARS-CoV-2 Vaccine (CoronaVac).Vaccines (Basel). 2022 May 30;10(6):878.

7.  Shi N, Yang Q, Zhang H, Lu J, Abulimiti A, Cheng J, Lin H, Yang X, Wang Y, Tong L, Wang T, Zhang X, Chen H, Xia Q*. Restoration of dystrophin expression in vivo by suppressing a nonsense mutation through the incorporation of unnatural amino acids. Nat Biomed Eng. 2022 Feb;6(2):195-206. (Highlighted by Nat Biotechnol)

8.  Zhang RR, Ye Q, Li XF, Deng YQ, Xu YP, Huang XY, Xia Q*, Qin CF*. Construction and characterization of UAA-controlled recombinant Zika virus by genetic code expansion.Sci China Life Sci. 2021 Jan;64(1):171-173.

9.  Zhao L, Yan Y, Dai Q, Li X, Xu K, Zou G, Yang K, Li W, Guo X, Yang J, Li Y, Xia Q, Cao R, Zhong W*. Development of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral Potentials.Antimicrob Agents Chemother. 2020 Jun 23;64(7): e00222-20.

10.  Yi F, Zhang P, Wang Y, Xu Y, Zhang Z, Ma W, Xu B, Xia Q, Du Q*. Long non-coding RNA slincRAD functions in methylation regulation during the early stage of mouse adipogenesis.RNA Biol. 2019 Oct;16(10):1401-1413.

11.  Si L, Meng K, Tian Z, Zhang Z, Soloveva V, Li H, Fu G, Xia Q, Xiao S, Zhang L, Cunningham J. M, Zhou D.* Triterpenoids manipulate a broad range of virus-host fusion via wrapping the HR2 domain prevalentin viral envelopes. Sci Adv.2018 Nov 21;4(11):eaau8408.

12.  Wang W, Zhao Z, Zhang Z, Zhang C, Xiao S, Ye X, Zhang L, Xia Q*, Zhou D*. Redirect Killer T Cells via Displaying Azido Sugar for Tethering Ligands. Chembiochem. 2017 Nov 2; 18(21):2082-2086.

13.  Lu J, Zhang H, Chen X, Zou Y, Li J, Wang L, Wu M, Zang J, Yu Y, Zhuang W, Xia Q*, Wang J*. A small molecule activator of SIRT3 promotes deacetylation and activation of manganese superoxide dismutase. Free Radic Biol Med. 2017 Jul 12; 112: 287-297.

14.  Lu J, Xia Q, and Zhou Q. How to make insulin-secreting pancreatic ?cells for diabetes treatment. Sci China Life Sci, 2017 (3) :1-10.

15.  Xu H, Wang Y, Lu J, Zhang B, Zhang Z, Si L, Wu L, Yao T, Zhang C, Zhang L, Xia Q*, Zhou D*. Re-exploration of the codon context effect on amber codon-guided incorporation of non-canonical amino acids in E. coli by the blue-white screening assay. Chembiochem. 2016 Jul 1;17(13):1250-1256.

16.  Si L, Xu H, Zhou X, Zhang Z, Tian Z, Wang Y, Wu Y, Zhang B, Niu Z, Zhang C, Fu G, Xiao S, Xia Q, Zhang L, Zhou D*. Generation of Influenza A Viruses as Live but Replication-incompetent Virus Vaccines. Science, 2016 Dec 2;354(6316):1170-1173.

17.  Ariyachet C, Tovaglieri A, Xiang G, Shah MS, Richmond CA, Lu J, Verbeke C, Brown J, Shivdasani R, Breault D, Mahony S, Xia Q, Mooney D, and Zhou Q*. Engineered stomach tissues as a renewable source of functional beta-cells for blood glucose regulation. Cell Stem Cell, 2016 Mar 3;18(3):410-421.

18.  LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency. Zhang J, Ratanasirintrawoot S, Chandrasekaran S, Wu Z, Ficarro SB, Yu C, Ross CA, Cacchiarelli D, Xia Q, Seligson M, Shinoda G, Xie W, Cahan P, Wang L, Ng SC, Tintara S, Trapnell C, Onder T, Loh YH, Mikkelsen T, Sliz P, Teitell MA, Asara JM, Marto JA, Li H, Collins JJ, Daley GQ*. Cell Stem Cell. 2016 Jul 7;19(1):66-80.

19.  Yang L, Song L, Liu X, Xia Q, Bai L, Gao G, Wang Y, Wei Z, Bai C, Li G. The Maternal Effect Genes UTX and JMJD3 Play Contrasting Roles in Mus musculus Preimplantation Embryo Development. Sci Rep.2016 Jul 7; 6: 26711.

20.  Wu Y, Zhu H, Zhang B, Liu F, Chen J, Wang Y, Wang Y, Zhang Z, Wu L, Si L, Xu H, Yao T, Xiao S, Xia Q, Zhang L, Yang Z, Zhou D*. Synthesis of site-specific radiolabeled antibodies for radioimmunotherapy via genetic code expansionBioconjugate Chem. 2016 Oct 19; 27(10):2460-2468.

21.  Zhang B, Yang Q, Xu H, Wu Y, Wu L, Yao T, Zhang L, Xia Q*, Zhou D*. CRISPRi-Manipulation of Genetic Code Expansion via RF1 for Reassignment of Amber Codon in Bacteria. Sci Rep. 2016, Jan 28;6:20000.

22.  Lu J, Cheng K, Zhang B, Xu H, Cao Y, Guo F, Feng X, Xia Q*. Novel mechanisms for superoxide-scavenging activity of human manganese superoxide dismutase determined by the K68 key acetylation site. Free Radic Biol Med. 2015 Aug; 85:114-26.

23.  Lu J, Cao Y, Cheng K, Xu B, Wang T, Yang Q, Yang Q, Feng X, Xia Q*. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status. Exp Cell Res. 2015 Jun 10;334(2): 194-206.

24.  ChengKY, Guo F, Lu JQ, Cao YZ, Wang TC, Yang Q, Xia Q*MnTM-4-PyP Modulates Endogenous Antioxidant Responses and Protects Primary Cortical Neurons against Oxidative Stress. CNS Neurosci Ther. 2015 May;21(5):435-45.

25.  Zheng Y, Yu F, Wu Y, Si L, Xu H, Zhang C, Xia Q, Xiao S, Wang Q, He Q, Chen P, Wang J, Taira K, Zhang L, Zhou D*. Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion. Nucleic Acids Res. 2015 Jun 23; 43(11): e73.

26.  Xiong W, Zhao J, Yu H, Li X, Sun S, Li Y, Xia Q, Zhang C, He Q, Gao X, Zhang L, Zhou D*. Elevated expression of AKR1C3 increases resistance of cancer cells to ionizing radiation via modulation of oxidative stress.PLoS One. 2014 Nov 24; 9(11): e111911.

27.  Zhang Y, Xia Q, Yang XD*, Wang K. Metallostasis and metal-based drugs for Alzheimer’s disease. Sci China Chem. 2014, 44(4): 541-554.

28.  Huang HF, Guo F, Cao YZ, Shi W, Xia Q*. Neuroprotection by Manganese Superoxide Dismutase (MnSOD) Mimics: Antioxidant Effect and Oxidative Stress Regulation in Acute Experimental Stroke. CNS Neurosci Ther. 2012, Oct; 18(10): 811-8.

29.  Xia Q, Liu HX, Yang XD*, Wang K. The neural toxicity of lanthanides: An update and interpretations. Sci China Chem. 2012, 42(9): 1308-14.

30.  Xia Q*, Feng X, Huang H, Du L, Yang X*, Wang K. Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons. J Neurochem. 2011, Apr; 117(1): 38-47.

31.  Feng XD, Xia Q*, Yuan L, Huang HF, Yang XD, Wang K*. Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+Cell Biol Toxicol. 2011, Feb; 27(1): 1-12.

32.  Zhao MX, Li JM, Du L, Tan CP, Xia Q*, Mao ZW*, Ji LN. Targeted cellular uptake and siRNA silencing by quantum-dot nanoparticles coated with cyclodextrin coupled to amino acids. Chem Eur J. 2011, Apr 26; 17(18):5171-9.

33.  Zhao MX, Huang HF, Xia Q*, Ji LN, Mao ZW*. Cyclodextrin–folate complex-functionalized quantum dots for tumor targeting and site-specific labeling. J Mater Chem. 2011, 21, 10290–7.

34.  Feng X, Xia Q*, Yuan L, Yang X, Wang K*. Impaired mitochondrial function and oxidative stress in rat cortical neurons: implications for gadolinium-induced neurotoxicity. Neurotoxicology. 2010, Aug; 31(4): 391-8.

35.  Wang JT, Zheng XH, Xia Q, Mao ZW, Ji LN, Wang K.1,10-Phenanthroline platinum(II) complex: a simplemolecule for efficient G-quadruplex stabilization. Dalton Trans2010 Aug 21; 39(31): 7214-6.

36.  Wang JT#Xia Q#, Zheng XH, Chen HY, Chao H, Mao ZW, Ji LN. An effective approach to artificial nucleases using copper (II) complexes bearing nucleobases. Dalton Trans. 39(8), 2128-36.

37.  Xia Q*, Feng XD, Yuan L, Wang K, Yang XD*. Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures. Sci China Chem. 2010, Oct; 53 (10): 2193–9.

38.  Zhao MX, Xia Q*, Feng XD, Zhu XH, Mao ZW*, Ji LN, Wang K. Synthesis, biocompatibility and cell labeling of L-arginine- functionalbeta-cyclodextrin-modified quantum dot probes. Biomaterials.2010, May; 31(15): 4401-8.

39.  Zhao YB, Ye LH, Liu HX, Xia Q, Zhang Y, Yang XD*, Wang K. Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress. J Inorg Biochem. 2010 Apr;104 (4): 371-8.

40.  Xia Q, Yang XW, Yang XD*, Qian ZM, Wang K. Drug delivery via the transferring receptor-mediated endocytosis pathway. 41.  Hu P, Wu GW, Xia Q, Mao ZW*. Achievement in SOD Mimics with Antioxidant and Anti-Inflammation Functions. Progress in Chemistry, 2009, 21(5), 873-9.J Chin Pharm Sci. 2009, 18 (1): 1-7.

42.  Zhang L, Zhang Y, Xia Q, Zhao XM, Cai HX, Li DW, Yang XD*, Wang K, Xia ZL. Effective control of blood glucose status and toxicity in streptozotocin-induced diabetic rats by orally administration of vanadate in an herbal decoction. Food Chem Toxicol. 2008, 46(9): 2996-3002.

43.  Mao XQ, Zhang L, Xia Q, Sun ZF, Zhao XM, Cai HX, Yang XD*, Xia ZL and Tang YJ*. Vanadium-enriched chickpea sprout ameliorated hyperglycemia and impaired memory in streptozotocin-induced diabetes rats. BioMetals. 2008, 21(5): 563-570.

44.  Zheng YH, Xia ZL, Chen LB, Zhao XM, Xia Q, Song XJ*. Variations in blood pressure and heart rate in conscious rats with cervical lymphatic blockade. Chin J Physiol. 2008, 51(3): 178-85.

45.  Miao YY, Xia Q, Hou ZC, Zheng Y, Pan H, Zhu SG*. Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats. Biochem Biophys Res Commun. 2007, 359: 795-800.

46.  Zhang J, Xia Q, Sun R, Tian ZG*. Interleukin-15 promotes the commitment of cord blood CD34 stem cells into NK cells. J Microbiol Immunol. 2004, Feb, 2(1): 40-4

47.  Xia Q, Pang W, Pan H, Zheng Y, Kang JS, Zhu SG*. Effects of ghrelin on the proliferation and secretion of spleen T lymphocytes in mice. Regul Pept 2004, Nov 15; 122 (3): 173-8.

 

组内学生获得国家奖学金:

史宁宁,郑哲涛,吴雪胜,杨琦,王天畅,卢加琪,郭飞