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夏青

教授、博士生导师

  

夏青    教授  博导医学博士

细胞工程与治疗实验室

北京市“科技新星”获得者

科技部新药创制重大项目负责人

中国微循环学会肿瘤专业委员会副主任委员

地址:北京大学医学部药学楼国家应急防控药物工程技术研究中心军民融合创新中心

电话:86-10-82805091(o)

E-mail: xqing@hsc.pku.edu.cn

研究领域:前沿生物技术及再生医学

教育背景及工作经历:

2004年获北京大学医学博士,2004-2006无机化学博士后,曾在南加州大学药学院学习生物技术药物研发、哈佛医学院学习诱导多能干细胞的定向分化机制。硕士阶段(1997-2000)课题研究免疫细胞的肿瘤生物治疗,博士阶段(2001-2004)课题研究神经元的缺血损伤及保护途径,博后阶段(2004-2006)研究大分子脑内淋巴引流的途径,之后开展多项化学与医学密切交叉的科研课题。发表包括ScienceCell Stem Cell Sci AdvFree Radic Biol MedBiomaterialJ NeurochemNeurotoxicologyExp Cell ResCell Biol ToxicolChem Eur JJ Mater Chem 等国内外论文五十多篇论文,申请国际专利5项。2018年在研2项科技部重大新药创制项目、1项国家自然科学基金重大研究计划、重大1项国自然面上基金。参编国家“十三五”药理学双语教材,参与讲授《现代生物学技术》《化学生物学专业英文》等课程。目前担任中国微循环学会肿瘤专业委员会副主任委员,中国医促会临床微生物与感染分会常委,北京药学会药物化学生物学分会委员。

研究方向:

1. 针对单基因遗传疾病,包括溶酶体病、肌营养不良与难治性癫痫种无义突变类型,研发致病蛋白促进通读药物,同时开发新型单碱基编辑系统,用于单基因遗传病的临床治疗。

2. 制备新型工程细胞及类人器官制备:利用非天然糖分子,碱基,氨基酸制备新型生物药物工程细胞,用于蛋白药物的快速研发及生物治疗细胞的定向改造;应用前沿合成生物学和化学生物学技术改造基因密码子和蛋白翻译系统,制备新型干细胞组织器官,用于类器官组织重编程及功能重建;利用RNA基因编辑系统制备包装病毒的新型细胞系等。

在研课题:

1. 单基因遗传病的治疗:

无义突变通读药物的高通量筛选;

 建立单基因遗传病的iPS细胞库及干细胞基因编辑;

 制备单基因遗传病的干细胞及动物模型;

 抑制性tRNA的治疗作用及结构研究。

2. 新型细胞的制备及改造:

基于蛋白质翻译终止机器的“细胞工厂”的制备

类脑及类肺组织的重编程及功能重建

● CRISPR靶向RNA的单碱基编辑技术

● RNA单碱基编辑技术修饰RNA病毒基因组用于复制缺陷病毒疫苗的制备

噬菌体进化技术介导的人工氨基酸参与的蛋白质筛选

终止密码子在细菌中的重编译与蛋白质进化的关系

3. 病毒感染与包装机制研究:

病毒感染参与的中枢神经系统的发病机制研究

病毒辅助质粒联合PTC技术制备组织特性病毒载体

在研主持项目:

1. 国家科技部创新药物专项:新型工程细胞制备(*,2018-2020),主持

2. 国家科技部创新药物专项:基于细胞工厂的PTC技术与类脑及类肺组织器官的建立(No.2018ZX09711003-001-003,2018-2020),主持

3. 国家自然基金面上项目:应用非天然氨基酸系统修复肌肉干细胞及干性维持的调控机制(No.21672016,2017-2018),主持

4. 国家自然科学基金重大研究计划:基于病毒包膜蛋白时空动态修饰的病毒-细胞融合研究及化学干预、靶点发现和转化(No. 91753202, 2018-2021),参与

研究经历:

1. LAK细胞的肿瘤免疫治疗1997

2. 造血干细胞分化成NK细胞的关键细胞因子筛选1999

3. 神经肽Ghrelin对脑缺血的保护及治疗机制2001

4. 脑内大分子引流的途径2004

5. MRI核磁对比剂Gd-DTPA的神经毒性研究2007

6. MnSOD模拟物的合成及神经保护分子机制 2009

7. P53调控线粒体能量和氧化应激水平2011

8. Berberin抑制神经突触生长机制2013

长期招聘:

1. 长期招聘博士后: 本实验室招收干细胞生物学、分子生物学、病毒学、免疫学、结构生物学及药物化学专业博士后,并对医学与化学交叉领域的研究有浓厚兴趣,年薪按照25-35万/年(高于北大博雅博后),其余待遇同北大人事部要求。联系邮件:xqing@bjmu.edu.cn,请注明“博士后申请”。

2. 科研助理:招聘本科/硕士/博士毕业学生做科研助理,专业同博后招聘,年薪12-15万,要求:对科研有浓厚兴趣,偏好生物前沿新技术和交叉领域研究。博士毕业学生可申请北大正式编制。联系邮件:xqing@bjmu.edu.cn,请注明“科研助理申请”。

Papers (*corresponding author)  

1. 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. Adv2018, 11(4), in press. ( DOI: 10.1126/sciadv.aau8408)

2. 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.

3. 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.

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

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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 expansion. Bioconjugate Chem. 2016 Oct 19; 27(10):2460-2468.

11. 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.

12. 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.

13. Cheng KY, Guo F, Lu JQ, Cao YZ, Xia Q*. MnTM-4-Pyp protects cortical neurons against oxidative stress via induction of cellular antioxidant response. Int J Dep Neurosci. 2015 Dec;47(Pt A):101.doi:10.1016/j.ijde vneu.2015.04.276.

14. 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.

15. Cheng KY, 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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 Trans. 2010 Aug 21; 39(31): 7214-6.

27. 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. (# equal contribution) 

28. 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.

29. 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.

30. 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.

31. Xia Q, Yang XW, Yang XD, Qian ZM, Wang K. Drug delivery via the transferring receptor-mediated endocytosis pathway. J Chin Pharm Sci. 2009, 18 (1): 1-7.

32. 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.

33. 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.

34. Mao XQ, Zhang L, Xia Q, Sun ZF, ZhaoXM, 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.

35. 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.

36. Li DW, Zhao XM, Zhang L, Cai HX, Xia Q, Yang MF, Xia ZL. Effects of diabetes on expression of glucose transporters in rat brain. Chin J Diabetes, 2008, Dec, 16 (12), 755-6 (in Chinese).

37. Miao YY, Xia Q, Hou ZC, Zheng Y, Pan H, Zhu SG. Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats.Biochemical and Biophysical Research Communication. 2007, 359: 795-800.

38. Wang XJ, Xia Q, Cai HX, Xia ZL. Relation between rCBF and neuronal apoptosis in penumbra following focal cerebral infarction.Chinese Journal of Pathophysiology. 2006, 22(5): 968-71 (in Chinese).

39. Xia Q, Wang XJ, Xia ZL, Zhu SG. A study of cerebral flow and c-fos expression following focal cerebral infarction. Journal of Chinese Microcirculation. 2005, 9 (2): 95-9 (in Chinese).

40. Niu JZ, Wang XJ, Xia Q, Wang T, Xia ZL. Expressions of caspase-3 and caspase-9 in rats with focal cerebral infarction: characteristics of spatial distribution and law of time development. Chinese Journal of Clinical Rehabilitation. 2005, 9 (21): 26-7 (in Chinese).

41. Wang XJ, Xia Q, Cai HX, Yang L, Xia ZL. Salvia miltiorrhiza protects rat brain through overexpression of HSP70 after cerebral ischemia. Chinese Journal of Integrative Medicine on Cardia/Cerebraovascular Disease. 2005, 3 (2), 140-1 (in Chinese).

42. Niu JZ, Wang XJ, Xia Q, Sun BL, Xia ZL. Dynamical progression of temporal and profile of HSP70 and cell apoptosis following focal cerebral infarction.J Chin Microcirculation. 2005, 9 (2): 179-81 (in Chinese).

43. Wang XJ, Qu SQ, Xia Q, Xia ZL. Expression of caspase 3, 9 and the intervention effects of salvia miltiorrhiza in rats with focal cerebral infarction.Chin J Clinical Rehabilitation. 2005, 9 (33): 83-5 (in Chinese).

44. Zhang J, Xia QSun R, Tian ZG. Interleukin-15 promotes the commitment of cord blood CD34 stem cells into NK Cells. Journal of Microbiology and Immunology. 2004, Feb, 2(1): 40-4.

45. Wang XJ, Xia Q, Yang L, Cai HX, Xia ZL. Dynamical progression of the temporal profile of neuronal apoptosis and necrosis in rats following focal cerebral infarction.Chinese Journal of Clinical Rehabilitation. 2004, Dec, 8 (34): 7702-4 (in Chinese).

46. Xia Q, Pang W, Pan H, Zheng Y, Kang JS, Zhu SG. Effects of ghrelin on the poliferation and secretion of spleen T lymphocytes in mice. Regulatory Peptides. 2004, 122 (3): 173-8.

47. Zhang J, Xia QSun R, Tian ZG. The promoting effect of rhIL-15 on cord blood CD34+ stem cells commit to NK cells. Chin J Microbiol and Immunol. 2002, Jul, 22 (4): 350-3 (in Chinese).

48. Xia Q, Tian ZG. Surface markers of NK cell precursors activation. Shanghai J Immunol.2001, 21 (1): 60-1 (in Chinese).

49. Wei HM, Tian ZG, Feng JB, Xu T, Xia Q, Sun R. Co-expression of human IL-12 in insect cells transfected by double promoter baculovirus expression vector. Chin J Microbiol and Immunol. 2000, Nov, 20 (6): 584-7 (in Chinese).

50. Wang JF, Tian ZG, Zhang C, Liu JS, Zhang JH, Xia Q, Sun R, Zhang J. Preparation of purified CD34+ cells by Immunoaffinity column method. Shanghai J Immunol.2000, 20 (6): 362-4 (in Chinese).

51. Xia Q, Tian ZG. Effects of cytokines on differentiation regulation of early NK cells. Chin J Cancer Biother. 2000 Sep; 7(3) : 232-3 (in Chinese).

52. Xu T, Tian ZG, Zhang C, Zhang JH, Xia Q, Sun R. Preliminary study on the purification methods of human NK cells. Chin J Immunol.2000, 16 (11): 594-7 (in Chinese).

53. Xu T, Tian ZG, Zhang C, Zhang JH,Xia Q, Sun R. Preliminary study on the purification methods of human NK cells. Chin J Cancer Biother. 1999 Sep; 6(3):184 (in Chinese).

54.Xia Q, Tian ZG. Stem cell factor induces the differentiation of human umbilical cord blood NK cell precursors. Chin J Cancer Biother. 1999 Sep; 6(3):180-1 (in Chinese).   

课题组成员:

王宇,仝乐,牛振岚,杨柯宇,史宁宁,吴雪胜,郑哲涛,陈红民,王嫄,张晓东,肖辉

优秀毕业生:

杨琦(美国麻省医学院),王天畅,卢加琪(哈佛医学院),程阔原(美国马里兰大学),郭飞(英国牛津大学),曹元照(澳洲昆士兰大学),黄海锋(美国肯塔基大学),冯旭东(哈佛医学院儿童医院),吴骜州(美国约翰霍布金斯大学医学院)