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王凤山
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一、基本情况
   
王凤山,男,196117日生,博士研究生学历,教授,山东大学药学院院长,国家糖工程技术研究中心副主任,山东大学药学院生化与生物技术药物研究所所长,山东大学淄博生物医药研究院院长。国务院政府特殊津贴享受者,山东省泰山学者药学特聘专家。
   
主要学术兼职有:中国生物化学与分子生物学会工业生化与分子生物学分会理事长;中国药学会生化与生物技术药物专业委员会副主任委员;中国生化制药工业协会专家委员会委员;山东省药学会常务理事兼生化与生物技术药物专业委员会主任委员;山东省生物制药行业协会技术专家委员会委员;山东省医药生物技术学会常务理事;《中国生化药物杂志》副主编,《中国海洋药物》杂志、《药物生物技术》、Drug Discovery & Therapeutics 编委等。
   
山东省第十一届人民代表大会常务委员会委员。
二、学习经历
1978
10月~19827月:山东医学院药学系,获医学学士学位;
1983
8月~19867月:山东医科大学药学系,获生物药物学理学硕士学位;
1995
10月~199610月:英国伦敦大学Imperial College化学系,访问学者;
1998
3~20013月:华东理工大学生物工程学院,获生物化工工学博士学位。
三、工作经历
1982
7月~19837月:化工部勘探公司化肥厂职工医院(河南太康),药师;
1986
7月~198810月:山东医科大学药学院生化制药教研室,助教;
1988
10月~199411月:山东医科大学药学院生化制药教研室,讲师,秘书;
1994
12月~199812月:山东医科大学药学院生化制药教研室,副教授,秘书;
1999
1月~20007月:山东医科大学药学院生化制药教研室,教授,教研室主任;
2000
8月~20043月:山东大学药学院生化与生物技术药物研究所所长,制药工程系主任;
2004
4月~200712月:山东大学药学院院长助理,生化与生物技术药物研究所所长,制药工程系主任;
2007
5月~200712月:山东大学国家糖工程技术研究中心副主任;
2007
12月~今:山东大学药学院院长,国家糖工程技术研究中心副主任,生化与生物技术药物研究所所长;
2009
11~今:山东省重大新药创制中心理事会秘书长,山东省新药产业技术创新战略示范联盟秘书长。
2012
3~今:山东大学淄博生物医药研究院院长。
四、专业
   
微生物与生化药学。
五、研究方向与特色简介
1.
生物技术药物研究
   
主要进行多肽与蛋白质类药物的基因克隆、表达、分离纯化、结构分析、生物活性、药理作用等研究,还开展利用基因工程技术改造生产菌种的研究。开展了南瓜胰蛋白酶抑制剂ICMTI I)的基因克隆和在毕赤酵母中的表达研究,活性研究表明,重组CMTI I除了具有丝氨酸蛋白酶抑制活性外,还有强的抑瘤活性。开展了展胸腺免疫调节肽融合蛋白的基因克隆与表达研究,所得表达产物具有较好的免疫调节活性。开展了一种抗菌肽的基因克隆与表达研究,所得表达产物具有较强的杀菌活性,可继续进行新药开发,或用于畜牧或海产品养殖。开展了穿膜肽Tat PTD-内皮抑素融合蛋白的克隆、表达及其穿透眼球屏障及对视网膜血管增生抑制作用的研究(国家自然科学基金)。
2.
酶与蛋白质的化学修饰研究
   
酶与蛋白质作为药用的最大障碍是体内半衰期短和有抗原性,用无抗原性大分子对其进行化学修饰是解决这一障碍的有效途径。本方向主要开展用PEG和有生物活性的多糖对酶或蛋白质进行化学修饰的研究。开展的研究有LMWH-SOD结合物的构效关系及其防治脑血再灌流损伤研究(国家自然科学基金)、组织靶向肝素-SOD结合物和壳聚糖-SOD结合物的构效关系及对放射损伤的作用与机制研究(国家自然科学基金)、蛋白质和多肽药物的定点PEG修饰技术(十一五重大科技专项)、内皮抑素的结构修饰及其构效关系和作用机制研究(教育部博士点基金)、长效人血白蛋白的制备及其药理活性和药代动力学研究(山东省科学技术发展计划)。
3.
多糖类药物研究
   
主要开展生物多糖的制备、结构分析、活性研究与给药系统研究,包括生物提取和发酵法制备多糖、从海洋生物制备多糖、多糖衍生物的制备、多糖的单糖组成与连接方式分析、适合多糖给药的剂型研究。目前研究的多糖对象有透明质酸、低分子肝素、肝素、乌贼墨多糖及它们的衍生物等。正在承担的课题有具有MMP抑制活性的硫酸化乌贼墨多糖SIP-S的抗肿瘤转移作用及其机制研究(国家自然科学基金)。
六、主要科研成果
   
先后承担或参加科研课题30余项,其中国家863计划1项,国家自然科学基金6项,国家十一五重大科技专项孵化基地项目子课题2项,国家十二五重大科技专项1项,省部级和企业委托项目多项。先后获山东省教育委员会科学技术进步一等奖1项和二等奖2项、山东省医学科学技术进步二等奖1项和三等奖各1项、国家内贸局科技进步三等奖1项。在国内外学术期刊上发表论文280余篇,其中有60余篇在SCIEI收录的杂志上发表。获得专利7项,取得新药证书2项,主编、副主编著作和教材9部,参编著作有10余部。
七、近年发表的代表性论文 
1. Pingli Li, Xinke Zhang, Yanna Cheng, Juan Li, Yuliang Xiao, QianZhang,AizhenZong, ChuanqingZhong,Fengshan Wang*. Preparation and in vitro immunomodulatory effect of curdlan sulfate. Carbohydrate Polymers, 2014, 102: 852– 861.
2.Yuhong Liu, Yuguo Liu, Haiqiang Jiang, LingchuanXu, YannaCheng,Peng George Wang, Fengshan Wang*. Preparation, antiangiogenic and antitumoral activities of thechemically sulfated glucan from Phellinusribis. Carbohydrate Polymers, 2014, 106: 42–48.
3. Yuliang Xiao, Pingli Li, Yanna Cheng, Xinke Zhang, Juzheng Sheng, Decai Wang, Juan Li, Qian Zhang, ChuanqingZhong, Rui Cao, Fengshan Wang*. Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with a-linolenic acid and the transport mechanism of the conjugates.International Journal of Pharmaceutics, 2014, 465: 143–158.
4.Maoxuan Liu, Haining Tan, Xinke Zhang, Zhang Liu, Yanna Cheng, Dongliang Wang, Fengshan Wang*. Hematopoietic effects and mechanisms of FufangE'jiao Jiang on radiotherapy and chemotherapy-induced myelosuppressed mice.Journal of Ethnopharmacology, 2014, 152: 575–584.
5.Lian Li, HengchangZang, Jun Li, Dejun Chen, Tao Li, Fengshan Wang*. Identification of anisodamine tablets by Raman and near-infrared spectroscopy with chemometrics. SpectrochimicaActa Part A: Molecular and Biomolecular Spectroscopy, 2014, 127: 91–97. 
6. XinMeng, Wenlong Yao, Jiansong Cheng, Xu Zhang, Lan Jin, Hai Yu, Xi Chen, Fengshan Wang*, Hongzhi Cao*. RegioselectiveChemoenzymatic Synthesis of GangliosideDisialylTetrasaccharide Epitopes. J. Am. Chem. Soc. , 2014, 136, 5205−5208.
7. Zhang Liu, ShengliJi, Juzheng Sheng, Fengshan Wang*.Pharmacological effects and clinical applications of ultra low molecular weight heparins.Drug Discoveries & Therapeutic, 2014, 8(1):1-10.
8. XuepingGuo, Yanli Shi, Juzheng Sheng, Fengshan Wang*. A Novel Hyaluronidase Produced by Bacillus sp. A50. PLOS ONE, 2014, 9(4): e94156. 
9.Pingli Li, Haining Tan, DongqingXu, Fengxin Yin, Yanna Cheng, XinkeZhang,Yuhong Liu,Fengshan Wang*. Effect and mechanisms of curdlan sulfate on inhibiting HBV infection and acting as an HB vaccine adjuvant. Carbohydrate Polymers, 2014, 110: 446–455.
10.AizhenZong, Ting Zhao, Yan Zhang, Xinlei Song, Yikang Shi, Hongzhi Cao, Chunhui Liu, Yanna Cheng, XianjunQu, Jichao Cao,Fengshan Wang*. Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiellamaindroni ink.Carbohydrate Polymers, 2013, 91: 403– 409.
11. Jun Yan, Xi Chen, Fengshan Wang* and Hongzhi Cao*. Chemoenzymatic synthesis of mono- and di-fluorinated Thomsen–Friedenreich (T) antigens and their sialylated derivatives. Organic &Biomolecular Chemistry, 2013, 11(5): 842–848.
12. HengchangZang, Jinfeng Wang, Lian Li, Hui Zhang, Wei Jiang, Fengshan Wang*. Application of near-infrared spectroscopy combined with multivariate analysis in monitoring of crude heparin purification process. SpectrochimicaActa Part A: Molecular and Biomolecular Spectroscopy, 2013, 109: 8-13.
13.RongshuaiDuan, Xiang’e Chen, Fengshan Wang*, Tianmin Zhang, Peixue Ling*. Oral administration of heparin or heparosan increases the Lactobacillus population in gut microbiota of rats. Carbohydrate Polymers, 2013, 94: 100–105.
14.Huarong Shao, Guanying Han, Peixue Ling
, Xiqiang Zhu, Fengshan Wang, Lijuan Zhao, Fei Liu, Xia Liu, Guilan Wang, Yong Ying, Tianmin Zhang. Intra-articular injection of xanthan gum reduces pain and cartilage damage in a rat osteoarthritis model. Carbohydrate Polymers, 2013, 92: 1850–1857. 
15.Suyuan Cheng, Chaozhong Wang, Jing Li, Chenggang Liang* and Fengshan Wang*.Determination of hemocoagulaseagkistrodon in a pharmaceutical preparation by high-performance liquid chromatography with pre-column derivatization and fluorescence detection.Journal of Chromatographic Science, 2013, 51:552–559.
16. Juan Li, Yanna Cheng, Xinke Zhang, Lei Zheng, Zhen Han, Pingli Li, Yuliang Xiao, Qian Zhang, Fengshan Wang*. The in vivoimmunomodulatory and synergistic anti-tumor activity of thymosin a1–thymopentin fusion peptide and its binding to TLR2.Cancer Letters, 2013, 337: 237–247.
17. Pingli Li, Juzheng Sheng, Yuhong Liu, Juan Li, Jian Liu*, andFengshan Wang*. Heparosan-Derived Heparan Sulfate/Heparin-Like Compounds: One Kind of Potential Therapeutic Agents. Medicinal Research Reviews, 2013, 33(3): 665–692.
18. Bao-qiu Li, Shi-hong Fang, Xin Dong, Na Li, Ji-you Gao, Gui-qin Yang, Xian-chang Gong, Shu-juan Wang, Feng-shan Wang*. Pharmacokinetics, tissue distribution and excretion of manganese(III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenylporphyrin chloride, a novel superoxide dismutase mimic,inWistar rats. Eur J Drug MetabPharmacokinet, 2013, 38:245–253.
19. Bao-qiu LI, XinDONG ,Gui-qin YANG, Na LI, Ji-you GAO, Shi-hong FANG, Xian-chang GONG, Shu-juan WANG,Feng-shan WANG*. A Novel Superoxide Dismutase Mimic, HSJ-0017,Reduces Radiation-Induced and Chemotherapy-Induced Damage, Latin American Journal of Pharmacy (formerly ActaFarmacéuticaBonaerense), 2013, 32(2): 257-262.
20. Guanying Han, Guilan Wang, Xiqiang Zhu, Huarong Shao, Fei Liu, Peikun Yang, Yong Ying,Fengshan Wang*, Peixue Ling*. Preparation of xanthan gum injection and its protective effect on articular cartilage in the development of osteoarthritis.Carbohydrate Polymers, 2012,87: 1837– 1842.
21.HengchangZang, Lian Li,Fengshan Wang*, Qiong Yi, Qin Dong, Chunxiao Sun, Jinfeng Wang.A method for identifying the origin of chondroitin sulfate with near infrared pectroscopy.Journal of Pharmaceutical and Biomedical Analysis, 2012, 61: 224– 229. 
22. Ting Zhao Yan-Na Cheng, Hai-Ning Tan, Jin-Feng Liu, Huan-Li Xu, Guang-Li Pang, andFeng-Shan Wang*. Site-specific chemical modification of human serum albumin with polyethylene glycol prolongs half-life and improves intravascular retention in mice. Biol Pharm Bull, 2012, 35(3): 280-288.
23.Shuwen Yu, Guisheng Zhang, Wenpeng Zhang, HuanhuaLuo, LiyunQiu, Qingfeng Liu, Duxin Sun, Peng-George Wang* andFengshan Wang*. Synthesis and biological activities of a 3'-azido analogue of doxorubicin against drug-resistant cancer cells.International Journal of Molecular Sciences, 2012, 13, 3671-3684.
24
Xinke Zhang, Xue Zhang &Fengshan Wang*. Intracellular transduction and potential of Tat PTD and its analogs: from basic drug delivery mechanism to application. Expert Opin Drug Deliv, 2012, 9(4): 457-472.
25. Ting Zhao, Yang Yang, AizhenZong, Haining Tan, Xinlei Song, ShuoMeng, Chunxia Song, Guangli Pang, Fengshan Wang*. N-terminal PEGylation of human serum albumin and investigation of its pharmacokinetics and pulmonary microvascular retention.BioScience Trends, 2012; 6(2):81-88.
26. Xiumei Liu, Chunxiao Sun, HengchangZang, Weihong Wang, RuichenGuo and Fengshan Wang*.Capillary electrophoresis for simultaneous analysis of heparin, chondroitin sulfate and hyaluronic acid and its application in preparations and synovial fluid. Journal of Chromatographic Science, 2012, 50:373–379.
27. AizhenZong, Hongzhi Cao,Fengshan Wang*. Anticancer polysaccharides from natural resources: A review of recent research. Carbohydrate Polymers, 2012, 90: 1395–1410.
28. Tan HaiNing, Cao Ji Chao, Mu Guo Ying, Xiao Min, Wang Feng Shan*. Preparation, characterization and anti-angiogenesis activity of endostatin covalently modified by polysulfated heparin.Pharmazie, 2012, 67: 622–627.
29. Juan Li, Lei Zheng, Pingli Li, Fengshan Wang*. Intein-mediated expression, purification, and characterization of thymosin a1–thymopentin fusion peptide in Escherichia coli. Protein Expression and Purification, 2012, 84: 1–8.
30.AizhenZong, Ting Zhao, Yan Zhang, Xinlei Song, Yikang Shi, Hongzhi Cao, Chunhui Liu, Yanna Cheng, XianjunQu, Jichao Cao, Fengshan Wang*. Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiellamaindroni ink.Carbohydrate Polymers, 2013, 91: 403– 409.
31. Xiaojing Huang, Chunxia Song, ChuanqingZhong, Fengshan Wang*.Research progress in the radioprotective effect of superoxide dismutase. Drug Discoveries & Therapeutics, 2012, 6(4):169-177.
32.Haining Tan, Shenglin Yang, Chunhui Liu, Jichao Cao, Guoying Mu, Fengshan Wang*. Enhanced anti-angiogenesis and anti-tumor activity of endostatin by chemical modification with polyethylene glycol and low molecular weight heparin.Biomedicine & Pharmacotherapy, 2012, 66: 648–654.
33. Dongliang Wang, Maoxuan Liu, Jichao Cao, Yanna Cheng, Chen Zhuo, HongyanXu, ShoushengTian, Yan Zhang, Jian Zhang, andFengshan Wang*. Effect of Collacoriiasini (E’jiao) on D-galactose induced aging mice. Biol. Pharm. Bull. , 2012, 35(12): 2128–2132.
34. Jun Yan, Xi Chen, Fengshan Wang* and Hongzhi Cao*. Chemoenzymatic synthesis of mono- and di-fluorinated Thomsen–Friedenreich (T) antigens and their sialylated derivatives. Organic &Biomolecular Chemistry, 2012, DOI: 10.1039/c2ob26989a
35. Jingzong Qi, Qingli Wang, Zhenhang Yu, Xin Chen and Fengshan Wang*.  Innovative drug R&D in China.Nature Reviews Drug Discovery, 2011, 10(5): 333-334.   
36. Dong-Liang Wang, Fang-Hua Qi, Wei Tang*,Feng-Shan Wang*. Chemical constituents and bioactivities of the skin of BufobufogargarizansCantor.Chemistry & Biodiversity, 2011,
8(4): 559–567.   
37.Haining TAN, Guoying MU, Wei ZHU, Jinfeng LIU, and Fengshan WANG*. Down-regulation of vascular endothelial growth factor and Up-regulation of pigment epithelium derived factor make low molecular weight heparin-endostatin and polyethylene glycol-endostatin potential candidates for anti-angiogenesis drug. Biol Pharm Bull, 2011, 34(4): 545-550.   
38.ShuoMeng, HuanliXu and Fengshan Wang*. Research advances of antimicrobial peptides and applications in food industry and agriculture. Current Protein and Peptide Science, 2010, 11, 264-273.
39. Juan Li, Chun Hui Liu, Feng Shan Wang*. Thymosin alpha 1: Biological activities, applications and genetic engineering production. Peptides, 2010, 31(11): 2151–2158.
40. Jinfeng Liu, Xuan Wang, Haining Tan, Hong Liu, Yonggang Wang, Renqin Chen, Jichao Cao, Fengshan Wang*. Effect of heparin-superoxide dismutase on γ-radiation induced DNA damage in vitro and in vivo. Drug Discoveries & Therapeutics, 2010, 4(5):355-361.
41.
Cui X, Zhou S, Xu H, Zhao T, Liu A, Guo X,
Wang F*. Reversal effects of hyaluronan oligosaccharides on adriamycin resistance of K562/A02 cells. Anticancer Drugs, 2009, 20(9):800-806.
42. Xiangzhen Cui, HuanliXu, Shuai Zhou, Ting Zhao, Aihua Liu, XuepingGuo, Wei Tang, Fengshan Wang*. Evaluation of angiogenic activities of hyaluronan oligosaccharides of defined minimum size.Life Sciences, 2009, 85(15-16): 573–577.
43. Jingzong Qi, Yizhao Li, Hongwei Zhang, Yanna Cheng, Yongfu Sun, Jichao Cao, Ying Zhao, Fengshan Wang*. A novel conjugate of low-molecular-weight heparin and Cu,Zn-superoxide dismutase: Study on its mechanism in preventing brain reperfusion injury after ischemia in gerbils. Brain Research, 2009, 1260: 76–83.
44.Jinfeng Liu, Xuan Wang, Fengshan Wang*, Li Teng and Jichao Cao. Attenuation effects of heparin–superoxide dismutase conjugate on bleomycin-induced lung fibrosis in vivo and radiation-induced inflammatory cytokine expression in vitro. Biomedicine & Pharmacotherapy, 2009, 63: 484-491
45.Jinfeng Liu, Li Teng, Chunhui Liu, Likuan Hu, Yonggang Wang, Hong Liu,Fengshan Wang*. Augmented inhibitory effect of superoxide dismutase on superoxide anion release from macrophages by chemical modification with polysaccharide and attenuation effects on radiation-induced inflammatory cytokine expression in vitro.Journal of Drug Targeting, 2009, 17(3): 216-224.
46. J.Z. Sheng, P.X. Ling*, X.Q. Zhu, X.P. Guo, T.M. Zhang, Y.L.He and F.S. Wang*. Use of induction promoters to regulate hyaluronan synthase and UDP-glucose-6-dehydrogenase of Streptococcus zooepidemicus expression in Lactococcuslactis: a case study of the regulation mechanism of hyaluronic acid polymer. Journal of Applied Microbiology, 2009, 107: 136-144.
47. Haining Tan, Shenglin Yang, You Feng, Chunhui Liu, Jichao Cao, Guoying Mu and Fengshan Wang*. Characterization and secondary structure analysis of endostatin covalently modified by polyethylene glycol and low molecular weight heparin.Journal of Biochemistry, 2008, 144(2): 207-213.
48.Chunhui Liu, Xiaodong Li, Yuhua Li, You Feng andFengshan Wang*.Stuctutural characterization and antimutagenic activity of a novel polysaccharide isolated from Sepiellamaindroni ink. Food Chemistry, 2008, 110(4) : 807–813.
49. Yuhong Liu, Fengshan Wang*.Structural characterization of an active polysaccharide fromPhellinusribis. Carbohydrate Polymers, 2007, 70: 386-392.  
*
通讯作者.
八、获得专利
1.
一种超氧化物歧化酶结合物及其制备方法,专利号:ZL02110099.3
2
.含肝素类药物的脂质体软膏剂及其制备方法,专利号:ZL03112234.5
3.
一种内皮抑素结合物及其制备方法,专利号:ZL200610043873.6
4.
一种胸腺肽a1-胸腺五肽融合肽及其制备方法,专利号:ZL200810014124.X
5.
一种表达重组虹鳟鱼抗菌肽Oncorhyncin的酵母工程菌及制备方法,专利号: ZL 200810138204.6
6.
一株产谷胱甘肽的酵母工程菌及其在生产谷胱甘肽中的应用,专利号:ZL 201210042356.2
7.
一株枯草杆菌工程菌及其在生产肝素酶I中的应用,专利号:ZL 201210042866.X
8.
一种Tat PTD-Endostatin重组蛋白及其制备方法与应用,专利号:ZL 201210149201.9
九、出版著作
   
主编出版著作:《生化药物研究》,人民卫生出版社1997年;《生化制药学》,人民卫生出版社1998年;《生物药物研究进展》,人民卫生出版社2004年;《生物化学与生化技术》,人民卫生出版社2007年;《生物制药工艺学》(副主编),人民卫生出版社2007年;《超氧化物歧化酶》(副主编),华东理工大学出版社2009年;《基因工程药学》(副主编),人民卫生出版社2010年;《生物技术制药》,人民卫生出版社2011年;《酶与酶工程》(副主编),华东理工大学出版社,2012年。
   
参编的著作:《中国商品大辞典药品分册》,中国商业出版社1992年;《生物化学》,青岛海洋大学出版社1993年;《临床免疫学》,科学出版社2002年;《眼科药物的临床应用与研究》,中国医药科技出版社2002年;《分离纯化工艺原理》,中国医药科技出版社2002年;《实用生物制药学》,人民卫生出版社2007年;《发酵工艺学》(第二版),中国医药科技出版社2009年;《玻璃酸研究与应用》,人民卫生出版社2010年;《生物化学》(第二版),中国医药科技出版社2010年。
十、荣誉奖励
1. 1992
年被评选为山东医科大学十佳青年教师
2. 1995
8月被中国民主促进会山东省委员会评为民进山东省先进会员 
3. 1998
年被评选为山东医科大学跨世纪学科带头人后备人才
4. 2004
年被评选为“2004年山东大学十大优秀教师
5. 2005
4月入选山东省卫生系统第二批中青年重点科技人才;
6. 2004
年山东大学十大优秀教师;
7. 2005
年山东省参政议政先进个人;
8. 2008
年被评为山东大学第四届教学名师  
9. 2011
1130日被中共中央统战部、人力资源和社会保障部、各民主党派中央、全国工商联各民主党派、工商联和无党派人士为全面建设小康社会作贡献先进个人称号;
10. 2012
14日被评为山东大学2011年度十大新闻人物
11. 2012
年被评为山东大学第四届我心目中的好导师
 
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