何山(宁大教授)

时间:2024-03-04 17:21:17编辑:小简

何山(宁大教授)的个人简介

宁波大学食品与药学学院教授、博导、海洋药物研究所所长、PI,宁波大学李达三叶耀珍伉俪李本俊海洋生物医药研究中心常务副主任,海洋生物医药国家111引智基地负责人。

2009年获浙江大学化学博士学位(导师:潘远江教授,国家杰青),曾在美国华盛顿州立大学从事博士后研究(合作导师:Norman Lewis教授,苏格兰科学院院士),2011年起在宁波大学任教至今,2015年获国家留学基金资助赴美国东北大学从事访问学者研究(合作导师:Slava Epstein教授,新型微生物培养技术先驱)。入选浙江省钱江人才计划(2012),宁波大学首批浙东青年学者(2015),宁波市领军与拔尖人才计划(2015),浙江高校中青年学科带头人(2017)。

曾多次受邀在第14届全国海洋药物学术年会(2019)、海洋领域面向2035年中长期科技规划战略研讨会(2019)、第9届菲律宾细胞生物学学会国际学术年会(2018)、第3届亚洲药学联盟国际研讨会(2017)等国内外重要学术会议上作大会报告。目前担任中国药学会海洋药物专业委员会委员、浙江省药学会海洋药物专业委员会委员、宁波市“科技创新2025”重大专项生物医药领域专家组成员等学术兼职。

发表SCI论文79篇(其中第一作者/通讯作者论文45篇),包括本领域主流期刊J. Org. Chem., ACS Chem. Neurosci., J. Chromatogr. A, Front. Microbiol., Appl. Microbiol. Biotechnol. , Mar. Drugs, Harmful Algae, Int. J. Syst. Evol. Microbiol., 总影响因子大于250,他引1000次以上。

教育背景

2000.09- 2004.06 浙江大学 化学系 本科
2004.09―2009.06 浙江大学 化学系 博士
2009.07―2011.05 美国华盛顿州立大学 生物化学研究所 博士后

代表论文

主要研究方向:海洋药用生物资源与创新药物研究

(1)海洋药物先导化合物发现。在国际上首次从30余种海洋生物中发现新化合物123个,新骨架化合物8个。通过高通量活性筛选,获得了3个抗阿尔兹海默症(AD)先导化合物,与宁波大学医学院崔巍教授合作,首次报道了Eckmaxol和Fucoxanthin等抗AD先导化合物的作用机制(ACS Chem. Neurosci.2018, 9, 1349?1356;Oxid. Med. Cell. Longev.2017, 6792543;Mar. Drugs2017, 15, 260)。此外,还发现了7个抗肿瘤(Harmful Algae2016, 58, 66u201373;Appl. Microbiol. Biotechnol.2014, 98, 4369-4377;Mar. Drugs2019, 17, 283)、5个抗菌(Front. Microbiol.2019, 10, 2846;Mar. Drugs2019, 17, 344;J. Antibiot.2018, 71, 902-904)药物先导化合物。为开发具有知识产权的新药奠定了基础。

(2)海洋天然产物高效制备新方法。针对“蓝色药库”药源瓶颈的高效制备关键技术难题,建立了Eckmaxol、Macrolactins等20余种天然药物先导化合物的高效分离纯化新方法,取得了系列研究成果(J. Chromatogr. A2013, 1272, 15-19;J. Sep. Sci.2019, 42, 2510u20132516;Mar. Drugs2018, 16, 73)。实现了从粗提物到纯化合物的一步式制备分离,回收率达到90%以上,高效制备方法的建立将加速海洋活性物质的新药创制进程。

(3)海洋“难培养”微生物新资源挖掘。针对99%以上海洋微生物无法在实验室常规条件下培养的关键技术难题,与Slava Epstein教授开展国际合作,首次改进和运用iChip、Diffusion Chamber等新型微生物原位培养技术深入挖掘海洋“难培养”微生物新资源,已发现新种378个,随机培养的出新率达到50%以上,目前已完成并发表了其中8个海洋微生物新种的系统分类鉴定与基因组分析(Int. J. Syst. Evol. Microbiol.2019, 69, 3293u20133298;Int. J. Syst. Evol. Microbiol.2018, 68, 2813-2818;Antonie van Leeuwenhoek2018, 111, 1855u20131862),从中发现了一系列新天然产物(Chem. Biodivers.In press,2020,中国药学会海洋药物专业委员会专刊),为突破海洋微生物资源瓶颈奠定了坚实基础。

(4)海洋“中光层”生物新资源探索。作为我国首位下潜深度达到100米的国际认证科学潜水员,于2019年牵头建立了国内首个海洋“中光层”(深度30-150米,占海洋生物多样性80%以上)科学潜水团队,率先在我国西沙群岛和菲律宾Apo Reef(与菲律宾大学合作)等海域启动了海洋“中光层”生物资源探索与系统挖掘工作,已采集中光层海绵、软珊瑚、柳珊瑚等30余种,设计运用新型微生物培养技术“连续流生物反应器”,实现了海绵共附生“难培养”微生物的实验室高效培养,已发现微生物新种50余个。探索和构建海洋“中光层”生物资源库对我国海洋生物学研究具有战略意义。

1. Weiyan Zhang, Can Chen, Ye Yuan, Dengquan Su, Lijian Ding, Slava S Epstein*,Shan He*.Pararhodobacter marinussp. nov., a bacterium isolated from marine sediment in the East China Sea and emended description of the genus Pararhodobacter.International Journal of Systematic and Evolutionary Microbiology2019,69, 3293u20133298.

2. Ning Wang, Panpan Qiu, Wei Cui, Xiaojun Yan, Bin Zhang*,Shan He*. Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present).Current Medicinal Chemistry2019,26, accepted.

3. Lijian Ding, Lu Ren, Shuang Li, Jingjing Song, Zhiwen Han,Shan He*, Shihai Xu*. Production of New Antibiotic 4-Hydroxy-α-Pyrones by a Marine FungusAspergillus nigerCultivated in Solid Medium.Marine Drugs2019,17, 344.

4. Xiaoping He, Lijian Ding*, Mengqi Yi, Jianzhou Xu, Xuezhen Zhou, Weiyang Zhang,Shan He*. Separation of five diketopiperazines from the marine fungusAlternaria alternateHK-25 by high-speed counter-current chromatography.Journal of Separation Science2019,42, 2510u20132516.

5. Liming Huang, Lijian Ding*, Xiaohui Li, Ning Wang, Yushan Yan, Mengxiang Yang, Wei Cui, C. Benjamin Naman, Kejun Cheng, Weiyan Zhang, Bin Zhang, Haixiao Jin,Shan He*. A new lateral root growth inhibitor from the sponge-derived fungusAspergillussp. LS45.Bioorganic & Medicinal Chemistry Letters2019,29, 1593u20131596.

6. Lijian Ding*, Te Li, Xiaojian Liao,Shan He*, Shihai Xu*. Asperitaconic acids Au2013C, antibacterial itaconic acid derivatives produced by a marine-derived fungus of the genusAspergillus.The Journal of Antibiotics2018,71, 902-904.

7. Weiyan Zhang, Ye Yuan, Dengquan Su, Lijian Ding, Xiaojun Yan, Min Wu, Slava S. Epstein*,Shan He*.Saccharospirillum mangrovisp. nov., a bacterium isolated from mangrove sediment.International Journal of Systematic and Evolutionary Microbiology2018,68, 2813-2818.

8. Jialing Wang, Jiachen Zheng, Chunhui Huang, Jiaying Zhao, Jiajia Lin, Xuezhen Zhou, C. Benjamin Naman, Ning Wang, William H. Gerwick, Qinwen Wang, Xiaojun Yan, Wei Cui*,Shan He*. Eckmaxol, a Phlorotannin Extracted fromEcklonia maxima, Produces Anti-β-amyloid Oligomer Neuroprotective Effects Possibly via Directly Acting on Glycogen Synthase Kinase 3β.ACS Chemical Neuroscience2018,9, 1349?1356.

9. Yong Liu, Xuezhen Zhou, C. Benjamin Naman, Yanbin Lu, Lijian Ding*,Shan He*. Preparative Separation and Purification of Trichothecene Mycotoxins from the Marine FungusFusariumsp. LS68 by High-Speed Countercurrent Chromatography in Stepwise Elution Mode.Marine Drugs2018,16, 73.

10. Jiajia Lin, Jie Yu, Jiaying Zhao, Ke Zhang, Jiachen Zheng, Jialing Wang, Chunhui Huang, Jingrong Zhang, Xiaojun Yan, William H. Gerwick, Qinwen Wang, Wei Cui*,Shan He*. Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells.Oxidative Medicine and Cellular Longevity2017,2017, 6792543.

11. Fang Fang, Jiaying Zhao, Lijian Ding, Chunhui Huang, C. Benjamin Naman,Shan He*, Bin Wu , Peng Zhu, Qijun Luo, William H. Gerwick, Xiaojun Yan, Qinwen Wang, Zaijun Zhang, Wei Cui*. 5-Hydroxycyclopenicillone, a New β-Amyloid Fibrillization Inhibitor from a Sponge-Derived FungusTrichodermasp. HPQJ-34.Marine Drugs2017,15, 260.

12. Pengjie Cai,Shan He*, Chengxu Zhou, Allen R. Place, Saddef Haq, Lijian Ding, Haimin Chen, Ying Jiang, Cheng Guo, Yaru Xu, Jinrong Zhang, Xiaojun Yan*. Two new karlotoxins found inKarlodinium veneficum(strain GM2) from the East China Sea.Harmful Algae2016,58, 66u201373.

13. Jiajia Lin, Ling Huang, Jie Yu, Siying Xiang, Jialing Wang, Jinrong Zhang, Xiaojun Yan, Wei Cui*,Shan He*, Qinwen Wang*. Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterasein Vitro.Marine Drugs2016,14, 67.

14. Binbin Gu, Yanying Zhang, Lijian Ding,Shan He*, Bin Wu, Junde Dong, Peng Zhu, Juanjuan Chen, Jinrong Zhang, Xiaojun Yan*. Preparative Separation of Sulfur-Containing Diketopiperazines from Marine FungusCladosporiumsp. Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode.Marine Drugs2015,13, 354-365.

15. Lijian Ding,Shan He*, Xiaojun Yan*. Efficient preparation of pseudoalteromone A from marinePseudoalteromonas rubraQD1-2 by combination of response surface methodology and high-speed counter-current chromatography: a comparison with high-performance liquid chromatography.Applied Microbiology and Biotechnology2014,98, 4369-4377.

16. Binbin Gu,Shan He*, Xiaojun Yan, Lixin Zhang*. Tentative biosynthetic pathways of some microbial diketopiperazines.Applied Microbiology and Biotechnology2013,97, 8439u20138453.

17.Shan He*, Xiaojun Yan*. From Resveratrol to Its Derivatives: New Sources of Natural Antioxidant.Current Medicinal Chemistry2013,20, 1005-1017.

18.Shan He, Hongqiang Wang, Peng Zhu, Juanjuan Chen, Rui Yang, Xiaojun Yan*. Preparative Isolation and Purification of Macrolactin Antibiotics from Marine BacteriumBacillus amyloliquefaciensusing High-Speed Counter-Current Chromatography in Stepwise Elution Mode.Journal of Chromatography A2013,1272, 15-19.

19.Shan He, Liyan Jiang, Bin Wu, Chang Li, Yuanjiang Pan*. Chunganenol: An Unusual Antioxidative Resveratrol Hexamer fromVitis chunganensis.Journal of Organic Chemistry2009,74, 7966-7969.

20.Shan He, Liyan Jiang, Bin Wu, Yuanjiang Pan, Cuirong Sun*. Pallidol, a resveratrol dimer from red wine, is a selective singlet oxygen quencher.Biochemical and Biophysical Research Communications2009,379, 283u2013287.

21.Shan He, Yanbin Lu, Liyan Jiang, Bin Wu, Feiying Zhang, Yuanjiang Pan*. Preparative isolation and purification of antioxidative stilbene oligomers fromVitis chunganensisusing high-speed counter-current chromatography in stepwise elution mode.Journal of Separation Science2009,32, 2339-2345.

22.Shan He, Bin Wu, Yuanjiang Pan*, Liyan Jiang. Stilbene Oligomers fromParthenocissus laetevirens: Isolation, Biomimetic Synthesis, Absolute Configuration and Implication of Antioxidative Defense System in the Plant.Journal of Organic Chemistry2008,73, 5233-5241.

23.Shan He, Cuirong Sun, Yuanjiang Pan*. Red Wine Polyphenols for Cancer Prevention.International Journal of Molecular Sciences2008,9, 842- 853.

24.Shan He, Yanbin Lu, Bin Wu, Yuanjiang Pan*. Isolation and purification of antioxidative isomeric polyphenols from the roots ofParthenocissus laetevirensby counter-current chromatography.Journal of Chromatography A2007,1151, 175- 179.

荣誉奖项

获2012-2013年度宁波市优秀博士后荣誉称号;

获2018年宁波市科学技术奖二等奖(排名第一);

获2019年浙江省自然科学奖二等奖(排名第一)。

科研项目

1. 国家自然科学基金(NSFC)面上项目,基于iChip技术的海洋“未培养”微生物资源挖掘及新天然产物发现Resource mining of marine "uncultured" microbes by iChip and new natural products discovery(41776168),2018.01-2021.12

2. 国家自然科学基金(NSFC)青年项目,海洋Uncultured 放线菌资源挖掘及新天然产物发现Resource Mining of Marine Uncultured Actinomycetes and Discovery of New Natural Products(41306134),2014.01-2016.12

3. 国家外专局/教育部111计划,海洋生物医药创新引智基地(D16013),2016.08-2021.08

4. 国家科技部(MOST)重点研发计划项目子课题,深海多孔动物门药物先导化合物的高效筛选与发现(2018YFC0310902),2018.08-2021.12

5. 国家科技部(MOST)星火计划,褐藻多酚作为大黄鱼饲料添加剂的应用与推广(2013GA701024),2013.01-2014.12

6. 教育部(MOE)博士点基金,卡罗藻毒素高效制备及其在养殖水域中的快速检测新方法研究(20133305120007),2014.01-2016.12

7. 浙江省自然科学基金(Zhejiang NSF),基于高速逆流色谱的卡罗藻毒素高效制备及新天然产物发现(LQ13B020004),2013.01-2015.12

8. 浙江省科技厅(Science Technology Department of Zhejiang Province)钱江人才计划,通过氧化胁迫葡萄科植物产生新型抗脑卒中先导化合物的研究(2012R10068),2012.08-2013.12

9. 浙江省科技厅(Science Technology Department of Zhejiang Province)重点科技创新团队子课题,海洋蓝细菌中新型抗肿瘤药物的开发(2012R10029-2),2011.04-2014.06

10. 宁波市科技局(Science Technology Department of Ningbo City)富民项目,海洋抗菌微生物产业化研究及其在大黄鱼养殖中的应用示范(2017C10016),2017.01-2019.12

11. 宁波市自然科学基金(Ningbo NSF),白藜芦醇低聚体生物合成诱导及聚合度与神经保护的构效研究(2013A610278),2013.02-2015.01

12. 宁波市海洋局(Marine Department of Ningbo City)海洋经济创新发展示范项目,宁波海洋生物高值利用公共服务平台-宁波海洋微生物资源开发利用子平台(NBHY-2017-P2),2018.03-2020.12

13. 宁波市科技局(Science Technology Department of Ningbo City),宁波市海洋生物产业调研,2016.11-2017.06

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