沈玉先:博士,教授(二级岗),博士生导师,教育部“新世纪优秀人才支持计划”入选者,安徽省领军人才团队带头人,安徽省学术技术带头人,首批安徽省高校“拔尖人才”。
研究方向:功能性蛋白与药物作用靶点
(Functionalproteins and the targets fordrugtherapeutics)
(一)学历:
1984.09 -1989.06安徽医科大学医学系本科/学士
1989.09 -1992.06安徽医科大学药理学专业研究生/硕士
1997.09 -2000.06安徽医科大学药理学专业研究生/博士
(二)工作经历:
1992.07 -1995.06安徽医科大学临床药理研究所助教
1995.07 -1999.10安徽医科大学临床药理研究所讲师
1999.11-2003.10安徽医科大学临床药理研究所副教授
2003.02 -2004.08美国马利兰大学生物技术研究所博士后研究
2005.05 -2008.12中国科学技术大学生命科学院博士后研究
2003.11-2007.05安徽医科大学临床药理研究所教授
2007.06 -2010.06省部共建教育部重点实验室教授
2009.01 -2010.12安徽医科大学护理学院副院长
2010.07 -2012.05安徽医科大学基础医学院教授,常务副院长
2012.06 -至今安徽医科大学基础医学院教授,院长
(三)主要学术任职:
中国药理学会抗炎免疫专业委员会委员、世界中医药学会联合会中医药免疫专业委员会常务理事;安徽省药理学会常务理事;安徽省色谱学会常务理事;Journal of Pharmacological Science编委、中国药理学通报编委、安徽医科大学学报编委、NatComm、FreeRadicalBioMed、BrainBehaviorandImmunity、SciRep等10 余种SCI源期刊的审稿人。
(四)主持的科研项目:
1.国家自然科学基金面上项目:肝细胞源性神经营养因子MANF经外泌体靶向HSCs 的抗肝纤维化作用及机制研究,编号81673438(2017.1-2020.12)
2.国家自然科学基金面上项目:新型神经营养因子MANF对肝细胞癌的抑制作用及其机制研究,编号81372576(2014.1-2017.12)
3.国家自然科学基金面上项目:炎症诱导的ARMET转录激活及其对NF-κB信号通路的调节机制,编号81173074(2012.1-2015.12)
4.国家自然科学基金重大研究计划(培育项目):内质网应激在乙型肝炎-肝硬化-肝癌转化过程中的调节机制及相关药物作用靶分子筛选,编号91129729(2012.1-2014.12)
5.教育部博士点基金(博导类):炎症诱导的ARMET 转录激活及其对NF-κB信号通路的调节机制,编号20113420110004(2012.1-2014.12)
6.国家自然科学基金:内质网应激蛋白ARMET对关节炎滑膜细胞过度增殖的负性调控,编号81072651(2011.1-2011.12)
7.国家自然科学基金面上项目:泛素连接酶Hrd1介导的tau蛋白降解,编号30772557(2008.1-2010.12)
8.安徽省科技攻关计划:内质网应激蛋白stresslin检测方法的建立及临床应用,编号07010300191(2007.1-2009.12)
9.国家自然科学基金面上项目:泛素连接酶hHrd1 对a1-抗胰蛋白酶Z变异型的降解的调控机制,编号30572219 (2006.1-2008.12)
10.教育部重点项目:泛素连接酶hHrd1和异常磷酸化tau功能性相互作用研究,编号206067 (2006.1-2008.12)
11.教育部“新世纪优秀人才支持计划”:泛素-蛋白酶体通路调控a1-抗胰蛋白酶Z变异型的降解,编号NCET-04-0589(2005.1-2007.12)
12.中国博士后基金一等资助:泛素连接酶hHrd1 和异常磷酸化tau功能性相互作用研究,编号2005038011(2005.1-2007.12)
(五)主要荣誉:
2000 年获第四届中国药理学会Servier 青年药理学工作者奖;
2003 年入选首届安徽省高校拔尖人才;
2004 年入选教育部“新世纪优秀人才支持计划”;
2005 年获中国博士后基金一等资助;
2006 年入选安徽省学术科技带头人后备人选;
2007 年获安徽省人才开发基金资助;
2014 年入选安徽省学术科技带头人;
2017 年获得安徽省领军人才团队带头人;
2017 年获得“安徽省先进工作者”。
(六)代表性论著(*为通讯作者):
1. Wang D, Hou C, Cao Y, Cheng Q, Zhang L, Li H, Feng L, Shen Y*. XBP1 activation enhances MANF expression via binding to endoplasmic reticulum stress response elements within MANF promoter region in hepatitis B. Int J Biochem Cell Biol 2018; 99: 140-146. (IF=3.81)
2. Feng L, Zhang J, Zhu N, Ding Q, Zhang X, Yu J, Qiang W, Zhang Z, Ma Y, Huang D, Shen Y, Fang S,4, Yu Y, Wang H*, Shen Y*. Ubiquitin ligase SYVN1/HRD1 facilitates degradation of the SERPINA1 Z variant/alpha-1-antitrypsin Z variant via SQSTM1/p62-dependent selective autophagy. Autophagy 2017; 13(4): 686-702. (IF=11.1)
3. Zhang WP, Chen LH, Feng H, Wang W, Cai Y, Qi F, Tao XF, Liu J, Shen YJ, Ren XF, Chen X, Xu JM*, Shen YX*. Rifampicin-induced injury in HepG2 cells is alleviated by TUDCA via increasing bile acid transporters expression and enhancing the Nrf2-mediated adaptive response. Free Radical Biology and Medicine 2017; 112:24-35. (IF=6.02)
4. Song MM*, Xu HL, Liang JX, Xiang HH, Liu R, Shen YX*. Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery. Materials Science & Engineering C-Materials for Biological Applications 2017;77: 904-911. (IF=4.7164)
5. Zhang D, Li MM, Dong Y, Zhang XH, Liu XY, Chen ZM, Zhu YJ, Wang HM, Liu XW, Zhu JL, Shen YJ, Korner H, Ying SC*, Fang SY* and Shen YX*. 1α, 25-Dihydroxyvitamin D3 up-regulates IL-34 expression in SH-SY5Y neural cells. Innate Immunity 2017; 23(7): 584-591. (IF=2.8299)
6. Liu J, Tao X, Zhang J, Wang P, Sha M, Ma Y, Geng X, Feng L, Shen Y, Yu Y. Wang S, Fang S, Shen Y*. Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation. Oncotarget. 2016; DOI: 10.18632/oncotarget.8066. (IF=6.359)
7. Wang XY, Song MM, Bi SX, Shen YJ, Shen YX*, Yu YQ*. MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats. Int J Mol Sci 2016; 17(9). (IF=3.687)
8. Fang WJ, Han C, Zhang HB, Wei WM, Liu R, Shen YX*. Preparation of amino-functionalized magnetic nanoparticles for enhancement of bacterial capture efficiency. RSC Adv 2016; 6:67875. (IF=2.936)
9. Wu F, Wang P, Shen YX, Nobuo N. Noda, Zhang H*. Small differences make a big impact: Structural insights into the differential function of the 2 Atg8 homologs in C. elegans. Autophagy 2016;12(3):606-7. (IF=11.1)
10. Chen L, Feng L, Wang X, Du J, Chen Y, Yang W, Zhou C, Cheng L, Shen Y, Fang S, Li J*, Shen Y*. Mesencephalic astrocyte-derived neurotrophic factor is involved in inflammation by negatively regulating the NF-kB pathway. Sci Rep 2015; 5:8133. doi: 10.1038/srep08133. (IF=5.578)
11. Liu J, Sha M, Wang Q, Ma Y, Geng X, Gao Y, Feng L, Shen Y, Shen Y*. Small ubiquitin-related modifier 2/3 interacts with p65 and stabilizes it in the cytoplasm in HBV-associated hepatocellular carcinoma. BMC Cancer 2015, 15:675.
12. Liu J, Zhou C, Tao X, Feng L, Wang X, Chen L, Li C, Huang D, Fang S, Shen Y*. ER stress-inducible protein MANF selectively expresses in human spleen. Hum Immunol 2015, 76 (11):823-30.
13. Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H*. Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. Mol Cell 2015; 60 (6):914-29. (IF=14.248)
14. Chen L, Wan L, Du J*, Shen Y*. Identification of MANF as a protein interacting with RTN1-C. Acta Biochim Biophys Sin. 2014; pii: gmu125. [Epub ahead of print]
15. Yang W, Shen Y, Chen Y, Chen L, Wang L, Wang H, Xu S, Fang S, Fu Y, Yu Y*, Shen Y*. Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis. J Neurol Sci. 2014; 344 (1-2):129-38.
16. Wang L, Tang W, Jiang T, Lu P, Li Y, Sun A, Shen Y, Chen Y, Wang H, Zong Z, Wang Y, Chen L, Shen Y*. Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of Propofol. Neurochem Res. 2014; 39(9):1741-52.
17. Wang J, Chen Q, Wang X, Zu B, Xu J, Xu Y, Zuo X, Shen Y, Wang J, Shen Y*. Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus. Am J Med Sci. 2014 Sep 15. [Epub ahead of print] PubMed PMID: 25226532.
18. Chen Z, Zhu M, Pan X, Zhu Y, Yan H, Jiang T, Shen Y, Dong X, Zheng N, Lu J, Ying S*, Shen Y*. Inhibition of Hepatitis B virus replication by SAMHD1. Biochem Biophys Res Commun. 2014; 450(4):1462-8.
19. Wang L, Chen L, Wang Q, Wang L, Wang H, Shen Y, Li X, Fu Y, Shen Y*, Yu Y*. Circulating endothelial progenitor cells are involved in VEGFR-2-related
endothelial differentiation in glioma. Oncol Rep. 2014 Sep 5. doi: 10.3892/or.2014.3467.
20. Feng LJ, Jiang TC, Zhou CY, Yu CL, Shen YJ, Li J*, Shen YX*. Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis. Inflamm Res. 2014; 63(5):335-46.
21. Du J, An R, Chen L, Shen Y, Chen Y, Cheng L, Jiang Z, Zhang A, Yu L, Chu D, Shen Y, Luo Q, Chen H, Wan L, Li M, Xu X, Shen J. Toxoplasma gondii virulence factor ROP18 inhibits the host NF-κB pathway by promoting p65 degradation. J Biol Chem. 2014; 289(18):12578-92.
22. Chen Z, Zhong Y, Wang Y, Xu S, Liu Z, Baskakov IV, Monteiro MJ, Karbowski M*, Shen Y*, Fang S*. Ubiquitination-Induced Fluorescence Complementation (UiFC) for Detection of K48 Ubiquitin Chains In Vitro and in Live Cells. PLoS One. 2013; 8 (9). doi:10.1371/annotation/65881dc3-5bce-4f0b-9060-7079e16b 1877.
23. Shen Y, Sun A, Wang Y, Cha D, Wang H, Wang F, Feng L, Fang S*, Shen Y*. Upregulation of mesencephalic astrocyte-derived neurotrophic factor (MANF) in glial cells is associated with ischemia-induced glial activation. J Neuroinflammation. 2012, 9(1):254. doi: 10.1186/1742-2094-9-254. (IF=5.79).
24. Shen YX*, Sun AM, Fang S, Feng LJ, Li Q, Hou HL, Liu C, Wang HP, Shen JL, Luo J, Zhou JN*. Hrd1 Facilitates Tau Degradation and Promotes Neuron Survival. Curr Mol Med 2012, 12 (2): 138-52 (IF=5.22).
25. Cheng L, Chen Y, Chen L, Shen Y, Shen J, An R, Luo Q, Du J. Interactions between the ROP18 kinase and host cell proteins that aid in the parasitism of Toxoplasma gondii. Acta Trop. 2012; 122(3):255-60.
26. Xu Z, Shi H, Mei Q, Shen Y, Xu J. Effects of macrophage metalloelastase on the basic fibroblast growth factor expression and tumor angiogenesis in murine colon cancer. Dig Dis Sci. 2012; 57(1):85-91.
27. Du J, Chen L, Luo X, Shen Y, Dou Z, Shen J, Cheng L, Chen Y, Li C, Wang H, Yao X. 14-3-3zeta cooperates with phosphorylated Plk1 and is required for correct cytokinesis. Front Biosci (Schol Ed). 2012; 4:639-50.
28. Wang H, Li Q, Shen Y, Sun A, Zhu X, Fang S, Shen Y*. The ubiquitin ligase Hrd1 promotes degradation of the Z variant alpha 1-antitrypsin and increases its solubility. Mol Cell Biochem 2011; 346: 137-145.
29. Yu YQ, Liu LC, Wang FC, Liang Y, Cha DQ, Zhang JJ, Shen YJ, Wang HP, Fang S,
Shen YX*. Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection. J Cereb Blood Flow Metab 2010; 30:79-91 (IF=5.74).
30. Lijie Feng, Yuxian Shen*, Aimin Sun, Yujun Shen, Shengyun Fang, Jun Li* Endoplasmic reticulum stress is involved in okadaic acid-induced tau phosphorylation and neurotoxic effects of okadaic acid. Neural Regen Res2010; 5: 1534-1540
31. Wang W, Shen YX, Li J, Zhang SH, Luo QL, Zhong ZR, Jiang ZJ, Shen JL. Enhanced expression of the decoy receptor IL-13Ralpha2 in macrophages of Schistosoma japonicum-infected mice. Chin Med J (Engl). 2009; 122:1650-4.
32. Apostolou A, Shen Y, Liang Y, Luo J, Fang S. ARMET, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res. 2008; 314: 2454-67 (IF: 3.948).
33. Sun GP, Wang H, Xu SP, Shen YX, Wu Q, Chen ZD, Wei W. Anti-tumor effects of paeonol in a HepA-hepatoma bearing mouse model via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production. Eur J Pharmacol. 2008 28; 584(2-3):246-52.
34. Xu Z, Shi H, Li Q, Mei Q, Bao J, Shen Y, Xu J. Mouse macrophage metalloelastase generates angiostatin from plasminogen and suppresses tumor angiogenesis in murine colon cancer. Oncol Rep. 2008; 20(1):81-8.
35. Li Y, Shen YX*, Feng LJ, Liu LH, Chen FH, Wu Q, Wang Hua. Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis. Eur J Pharmacol 2007; 567: 166-70.
36. Shen Y, Ballar P, Apostolou A, Doong H, Fang SY. ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates. Biochem Biophys Res Commun 2007; 352: 919-924.
37. Shen YX*, Zhang GG, Liu LH, Wang H, Xu SY. Suppressive of effects of melatonin on amyloid b peptide-induced glial activation in rat hippocampus. Arch Med Res 2007; 38: 284-290.
38. Ballar P, Zhong Y, Nagahama M, Tagaya M, Shen Y, Fang S. Identification of SVIP as an endogenous inhibitor of ER-associated degradation. J Biol Chem 2007; 282:33908-14.
39. Yang H, Zhong XY, Ballar P, Luo SQ, Shen YX, Rubinsztein DC, Monteiro MJ, Fang SY. Ubiquitin ligase Hrd1 enhances the degradation and suppresses the
toxicity of polyglutamine-expanded huntingtin. Exp Cell Res 2007; 313: 538-50.
40. Liu YJ, Zhuang J, Zhu HY, Shen YX, Tan ZL, Zhou JN. Cultured rat cortical astrocytes synthesize melatonin: absence of a diurnal rhythm. J Pineal Res 2007; 43: 232-8.
41. Shen Y, Ballar P, Fang SY. Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin. Biochem Biophys Res Commun 2006; 349:1285-93.
42. Ballar P, Shen Y, Yang H, Fang SY. The Role of a Novel p97/Valosin-containing Protein-interacting Motif of gp78 in Endoplasmic Reticulum-associated Degradation.J Biol Chem 2006; 281:35359-68
43. Hou HL, Shen YX, Zhu HY, Sun H, Yan XB, Fang H, Zhou JN. Alterations of hHrd1 expression are related to hyperphosphorylated tau in the hippocampus in Alzheimer's disease.J Neurosci Res2006; 84:1862-70.
44. Zhong XY, Shen YX, Ballar P, Apostolou A, Agami R, Fang SY. Ubiquitin ligase gp78 enhances p97/VCP-polyubiquitin binding and promotes degradation of polyubiquitinated protein. J Biol Chem 2004; 279: 45676-45684
45. Yue L, Wang H, Liu LH, Shen YX*, Wei W*. Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflammatory factors. Acta Pharmacol Sin 2004; 25: 1182-5
46. Shen YX*, Xu SY, Wei W, et al. The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25-35 in middle-aged rats. J Pineal Res 2002; 32: 85-9.(IF=9.6)
47. Shen YX*, Xu SY, Wei W, et al. Melatonin blocks rat hippocampal neuronal apoptosis induced by amyloid beta-peptide 25-35.J Pineal Res 2002; 32: 163-7. (IF=9.6)
48. Shen YX*, Xu SY, Wei W, et al. Melatonin reduces memory changes and neural oxidation damage in mice treated with D-galactose. J Pineal Res 2002; 32: 173-8. (IF=9.6)
49. Shen YX*, Wei W, Xu SY. Protective effects of melatonin on the cortical -hippocampal neurotoxicity induced by amyloid beta-peptide 25-35. Acta Pharmacol Sin 2002; 23: 71-6.
50. Shen YX*, Wei W, Yang J, et al. Improvement of melatonin to learning and memory impairment induced by amyloid b-peptide 25~35 in elder Rats. Acta Pharmacol Sin2001; 22: 797-803.
(七)成果:
1. COX-2抑制剂靶向治疗消化系肿瘤的关键技术与应用. 2014年度安徽省科学技术奖二等奖,第二完成人。
2. 胶质瘤多模态磁共振成像的基础及临床应用. 2013安徽省科学技术奖二等奖,第三完成人。