PI简介：张 云　 研究员 博士生导师

44岁， 1984年毕业于华东理工大学，获学士学位。1987年赴法国巴斯德研究所进行联合培养，1992年获博士学位。1993－1995年在法国巴斯德研究所从事博士后研究。1997－1998年，美国新墨西哥大学医学院访问学者；1998-1999香港科技大学生物技术研究所访问学者；1999－2000年，中国科学院“知识创新”工程西南基地“动物活性蛋白多肽组学”学科团组学术带头人；2001年至今，中国科学院“知识创新”工程西南基地“动物毒素结构与功能”首席学科负责人。中科院昆明动物研究所所学术委员会委员；国家科技核心刊物“动物学研究”学报编委；国际毒素学会会刊《Toxicon》编委；国际生物毒素学会亚太地区理事；中国毒理学会生物毒素委员会理事；云南省动物学会理事；云南省生物化学学会理事。

研究方向

该研究小组长期系统开展两栖爬行动物毒素蛋白多肽分子生物多样性，结构与功能研究。通过对两栖爬行动物毒素蛋白多肽家族的结构变异与功能分化，作用机理和生物学意义进行的系统研究，为探索生物适应机制及其分子基础，功能基因组进化特征，人类自身生理、病理分子机制等科学问题提供了优良基础知识和研究模型，也为临床创新治疗药物的开发提供先导结构。长期从事蛋白多肽多基因家族分子功能基因组的克隆、表达、结构模拟及新分子构建研究工作；动物毒素功能蛋白多肽的作用机理(酶活性、配体-受体等)，构效关系研究以及毒素多基因家族分子与人内源性分子构效关系比较研究。目前主要开展两个方面的工作：一是构建在理论和应用上都有较大意义的有毒毒物(蛇、两栖类)毒腺cDNA库，获得200-300个目标蛋白酶基因克隆，测定全序列。竹叶青蛇毒类凝集素类物质结构与功能研究，生物活性测定，血小板膜位点探讨。二是分离纯化的大蹼铃蟾皮肤活性蛋白多肽的结构与功能研究，体内作用靶点探讨。两栖类皮肤活性蛋白多肽进一步分离及生物活性鉴定工作(主要指大蹼铃蟾和蟾蜍)。利用分子凝胶过滤，FPLC离子交换，HPLC进行传统中药蟾蜍皮肤分泌物分离纯化，将各成份作生物活性检测。进行各种动物内脏平滑肌的离体测定，广谱抗菌活性检测，膜片钳技术观察其对离子通道的影响；注重筛选具有心血管系统活性，免疫调节活性和抗微生物活性的新的两栖类皮肤活性肽。

科研任务（2003-今）

研究团队（2003-今）

发表论文

2008年发表论文

[1]He YY#, Liu SB, Lee WH, Qian JQ, Zhang Y*: Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom. Peptides 2008，29: 1692-1699.

[2]Zhao H#, Lee WH, Shen JH, Li H, Zhang Y*: Identification of novel semenogelin I-derived antimicrobial peptide from liquefied human seminal plasma. Peptides 2008, 29: 505-511.

[3]Zhao H#, Gan TX, Liu XD, Jin Y, Lee WH, Shen JH, Zhang Y*: Identification and characterization of novel reptile cathelicidins from elapid snakes. Peptides 2008，29: 1685-1691.

[4]Liu SB#, He YY, Zhang Y, Lee WH, Qian JQ, Lai R, Jin Y*: A novel non-lens betagamma-crystallin and trefoil factor complex from amphibian skin and its functional implications. PLoS ONE 2008，3: e 1770.

[5]Qian JQ#, Liu SB, He YY, Lee WH, Zhang Y*: betagamma-CAT, a non-lens betagamma-crystallin and trefoil factor complex from amphibian skin secretions, caused endothelium-dependent myocardial depression in isolated rabbit hearts. Toxicon 2008，52: 285-292.

[6]He YY#, Liu SB, Lee WH, Zhang Y*: Melanoma cell growth inhibition by betagamma-CAT, which is a novel non-lens betagamma-crystallin and trefoil factor complex from frog Bombina maxima skin.　  Toxicon 2008，52: 341-347.

[7]Qian JQ#, Liu SB, He YY, Lee WH, Zhang Y*: Acute toxicity of betagamma-CAT, a naturally existing non-lens betagamma-crystallin and trefoil factor complex from frog Bombina maxima skin secretions. Toxicon 2008, 52: 22-31.

2007年发表论文

[1]Guo XX#, Zeng L, Lee WH, Zhang Y*, Jin Y: Isolation and cloning of a metalloproteinase from king cobra snake venom. Toxicon 2007，49: 954-965.

[2]Jin Y#, Lee WH, Zhang Y*: Molecular cloning of serine proteases from elapid snake venoms. Toxion 2007, 49, 1200-1207.

[3]Jin Y#, Lee WH, Zeng L, Zhang Y*: Molecular characterization of L-amino acid oxidase from king cobra venom. Toxicon 2007, 50: 479-489.

2006年发表论文

[1]Zhao Y#, Jin Y, Lee WH, Zhang Y*: Isolation and molecular characterization of a novel lysozyme from toad skin secretions. Comp Biochem Physiol C Toxicol Pharmacol. 2006, 142: 46-52.

[2]Zhang YX#, Wang YY, Lee WH, Zheng YT, Zhang Y*: Apoptotic activity of frog Bombina maxima skin albumin. Comp Biochem Physiol B Biochem Mol Biol. 2006, 143: 153-159.

[3]Zhong SR#, Jin Y, Wu JB, Chen RQ, Jia YH, Wang WY, Xiong YL, Zhang Y*: Characterization and molecular cloning of dabocetin, a potent antiplatelet C-type lectin-like protein from Daboia russellii siamensis venom. Toxicon 2006, 47: 104-112.

[4]Wan SG#, Jin Y, Lee WH, Zhang Y*: A snake venom metalloproteinase that inhibited cell proliferation and induced morphological changes of ECV304 cells. Toxicon 2006, 47, 480-489.

[5]Wan SG#, Jin Y, Lee WH, Zhang Y*: Cloning of two novel P-III class metalloproteinases from Trimeresurus stejnegeri venom gland. Toxicon 2006, 47: 465-472.

[6]Du XY, Sim DS, Lee WH, Zhang Y*: Blood cells as targets of snake toxins. Blood Cells Mol Dis. 2006, 36: 414-421.

2005年发表论文

[1]Lee WH#, Li Y, Lai R, Li S, Zhang Y*: Wang W: Variety of antimicrobial peptides in the Bombina maxima toad and evidence of their rapid diversification. European Journal of Immunoloy 2005, 35: 1220-1229.

[2]Zhang YX#, Lai R, Lee WH, Zhang Y*: Frog albumin is expressed in skin and characterized as a novel potent trypsin inhibitor. Protein Sci. 2005, 14: 2469-2477.

[3]Lee WH#, Zhang J, Zhang YX, Jin Y, Lai R, Zhang Y*: Maximin 9, a novel free thiol containing antimicrobial peptide with anti-mycoplasma activity from frog Bombina maxima. FEBS Lett. 2005, 579: 4443-4448.

[4]Wang T#, Zhang J, Shen JH, Jin Y, Lee WH, Zhang Y*: Maximins S, a novel group of antimicrobial peptides from toad Bombina maxima. Biochem Biophys Res Commun. 2005, 327: 945-951.

[5]Zhang J#, Zhang Y, Wan SG, Wei SS, Lee WH, Zhang Y*: Bm-TFF2, a trefoil factor protein with platelet activation activity from frog Bombina maxima skin secretions. Biochem Biophys Res Commun. 2005, 330: 1027-1033.

[6]Lee WH#, Liu SB, Shen JH, Jin Y, Zhang Y*: Cloning of bradykinin precursor cDNAs from skin of Bombina maxima reveals novel bombinakinin M antagonists and a bradykinin potential peptide. Regulatory Peptides 2005, 127: 207-215.

[7]Lee WH#, Liu SB, Shen JH, Jin Y, Lai R, Zhang Y*: Identification and molecular cloning of a novel neuromedin U analog from the skin secretions of toad Bombina maxima. Regulatory Peptides 2005, 129: 43-47.

[8]Zhao Y#, Jin Y, Lee WH, Zhang Y*: Isolation and characterization of a 22-kDa protein with trypsin inhibitory activity from toad Bufo andrewsi skin. Toxicon 2005, 46, 277-281.

[8]Zhao Y#, Jin Y, Wang JH, Wang RR, Yang LM, Lee WH, Zheng YT, Zhang Y*: A novel heme-containing protein with anti-HIV-1 activity from skin secretions of Bufo andrewsi. Toxicon 2005, 46: 619-624.

[8]Shen JH#, Liu SB, Zhang YX, Jin Y, Lee WH, Zhang Y*: Cloning of novel bombesin precursor cDNAs from skin of Bombina maxima. Regulatory Peptides 2005, 132: 102-106.

[9]Zhao Y#, Jin Y, Wei SS, Lee WH, Zhang Y*: Purification and characterization of an irreversible serine protease inhibitor from skin secretions of Bufo andrewsi. Toxicon 2005, 46: 635-640.

2004年发表论文

[1]He YY#, Lee WH, Zhang Y*: Cloning and purification of a-neurotoxins from Ophiophagus hannah venom. Toxicon 2004, 44: 295-303.

[2]Tai H#, Wei Q, Jin Y, Su M, Song JX, Zhou XD, Ouyang HM, Wang WY, Xiong YL, Zhang Y*: TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb. Toxicon 2004, 44: 649-656.

2003年发表论文

[1]Lee WH#, Du XY, Lu QM, Clemetson KJ, Zhang Y*: Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thrombosis and Haemostasis 2003, 90: 662-671.

[2]Zhang YJ#, Wang JH, Lee WH, Wang Q, Liu H, Zheng YT, Zhang Y*: Molecular characterization of Trimeresurus stejnegeri venom L-amino acid oxidase with potential anti-HIV activity. Biochem Biophys Res Commun. 2003, 309: 598-604.

[3]Lai R#, Liu H, Lee WH, Zhang Y*: Bombinakinin M gene associated peptide, a novel bioactive peptide from skin secretions of the toad Bombina maxima. Peptides 2003, 24: 199-204.

[4]Lai R#, Liu H, Lee WH, Zhang Y*: Two novel Bv8-like peptides from skin secretions of toad Bombina maxima. Comp Biochem Physiol B 2003, 134: 509-514.

[5]Lee WH#, Zhuang QY, Zhang Y*: Cloning and characterization of a blood coagulation factor IX-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 2003, 41: 765-772.

[6]Lee WH#, Zhang Y*: Molecular cloning and characterization of a platelet glycoprotein Ib-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 2003, 41: 885-892.

[7]Lai R#, Liu H, Lee WH, Zhang Y*: Bombinakinin M gene associated peptide, a novel bioactive peptide from skin secretions of the toad Bombina maxima. Peptides 2003, 24: 199-204.

[8]Lai R#, Liu H, Lee WH, Zhang Y*: Two novel Bv8-like peptides from skin secretions of toad Bombina maxima. Comp Biochem Physiol B 2003, 134: 509-514.

[9]Lee WH#, Zhuang QY, Zhang Y*: Cloning and characterization of a blood coagulation factor IX-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 2003, 41: 765-772.

[10]Lee WH#, Zhang Y*: Molecular cloning and characterization of a platelet glycoprotein Ib-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 2003, 41: 885-892.

2002年发表论文

[1]Lai R#, Liu H, Lee WH, Zhang Y*: An anionic antimicrobial peptide from skin secretions of toad Bombina maxima. Biochem Biophys Res Commun. 2002, 295: 796-799.

[2]Lai R#, Zheng YT, Shen JH, Liu GJ, Liu H, Lee WH, Tang SZ, Zhang Y*: Antimicrobial peptides from the skin secretion of Chinese red belly toad Bombina maxima. Peptides 2002, 23: 427-435.

[3]Lai R#, Liu H, Lee WH, Zhang Y*: A novel probline rich bombesin-related peptide (PR-bombesin) from Bombina maxima. Peptides 2002, 23: 437-442.

[4]Lai R#, Liu H, Lee WH, Zhang Y*: Identification and cloning of a trypsin inhibitor from skin secretions of Chinese red belly toad Bombina maxima. Comp Biochem Physiol B 2002, 131: 47-53.

[5]Lai R#, Yang DM, Lee WH, Zhang Y*: Biological activities of skin secretions of Salamander Tylototriton verrucosus. J Natural Toxins 2002, 11: 245-250.

2001年以前发表论文

[1]Zhang Y, Wisner A, Xiong Y, Bon C: A novel plasminogen activator from snake venom. Purification, characterization, and molecular cloning. J Biol Chem. 1995，270:10246-10255.

[2]Lee WH, Zhang Y, Wang WY, Xiong YL, Gao R: Isolation and properties of a blood coagulation factor X activator from the venom of king cobra (Ophiophagus hannah). Toxicon 1995, 33: 1263-1276.

[3]Zhang Y, Wisner A, Maroun RC, Choumet V, Xiong Y, Bon C: Trimeresurus stejnegeri snake venom plasminogen activator. Site-directed mutagenesis and molecular modeling. J Biol Chem. 1997, 272: 20531-20537.

[4]Gao R, Zhang Y, Meng QX, Lee WH, Li DS, Xiong YL, Wang WY: Characterization of three fibrinogenolytic enzymes from Chinese green tree viper (Trimeresurus stejnegeri) venom. Toxicon 1998, 36: 457-467.

[5]Zhang Y, Lee WH, Gao R, Xiong YL, Wang WY, Zhu SW: Effects of Pallas' viper (Agkistrodon halys pallas) venom on blood coagulation and characterization of a prothrombin activator. Toxicon 1998, 36: 143-152.

[6]Zhang Y, Gao R, Lee WH, Zhu SW, Xiong YL, Wang WY: Characterization of a fibrinogen-clotting enzyme from Trimeresurus stejnegeri venom, and comparative study with other venom proteases. Toxicon 1998, 36: 131-142.

[7]Zha HG, Lee WH, Zhang Y. Cloning of cDNAs encoding C-type lectins from Elapidae snakes Bungarus fasciatus and Bungarus multicinctus. Toxicon 2001, 39: 1887-1892.

申请专利

[1]张云，赖仞，郑永唐，唐绍宗，李文辉，大蹼铃蟾蛋白酶抑制剂及其制备方法和在制药中的应用。专利号：ZL00122416.6

[2]张云，赖仞，郑永唐，刘广杰，李文辉，唐绍宗，大蹼铃蟾多肽在制备抗肿瘤和艾滋病药物中的应用。专利号：ZL00122417.4

[3]张云，赖仞，郑永唐，唐绍宗，李文辉，大蹼铃蟾皮肤肽及其制备方法和在制药中的应用。专利号：ZL00122415.8

[4]张云，赖仞，郑永唐，李文辉，大蹼铃蟾抗精子多肽及其制备方法和在制药中的应用。专利号：ZL00130617.0

[5]张云，赖仞，郑永唐，李文辉，刘衡，刘广杰，抗肿瘤蛋白及其制备方法和其基因。专利号：ZL01107253.9

[6]张云，赖仞，刘衡，李文辉，抗微生物肽及其制备方法和其基因。专利号：ZL01107255.5

[7]张云，赖仞，刘衡，李文辉，血管扩张因子其制备方法和其基因。专利号：ZL01107254.7

[8]张云，赖仞，刘衡，李文辉，饱食因子及其制备方法。专利号：ZL021135169)。

[9]张云，赖仞，刘衡，李文辉，酸性抗菌肽及其基因和在制药中的应用。专利号：ZL021135150

[10]张云，赖仞，血管收缩因子及其制备方法和在制药中的应用。专利号：ZL021135177

奖励

2002 云南省科学技术奖一等奖（自然科学类）：“蛇毒蛋白酶结构与功能及其对血液凝固系统的作用”（张云，李文辉，熊郁良，王婉瑜，高荣）

2004 云南省科学技术奖二等奖（自然科学类）：“烙铁头属蛇毒蛋白的结构与功能研究”（熊郁良，王婉瑜，张云，吕秋敏，金杨，魏勤，陈润强，周兴丁）

　　　 实验室原核培养操作台

　  实验室真核培养间

张云研究员获“西部之光”先进个人荣誉称号