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何山
寧波大學海洋學院副教授
寧波大學食品與藥學學院教授、博導、海洋藥物研究所所長、PI,寧波大學李達三徠葉耀珍伉儷李本俊海洋生物醫藥研究中心常務副主任,海洋生物醫藥國家111引智基地負責人。
2009年獲浙江大學化學博士學位(導師:潘遠江教授,國家傑青),曾在美國華盛頓州立大學從事博士后研究(合作導師:Norman Lewis教授,蘇格蘭科學院院士),2011年起在寧波大學任教至今,2015年獲國家留學基金資助赴美國東北大學從事訪問學者研究(合作導師:Slava Epstein教授,新型微生物培養技術先驅)。入選浙江省錢江人才計劃(2012),寧波大學首批浙東青年學者(2015),寧波市領軍與拔尖人才計劃(2015),浙江高校中青年學科帶頭人(2017)。
曾多次受邀在第14屆全國海洋藥物學術年會(2019)、海洋領域面向2035年中長期科技規劃戰略研討會(2019)、第9屆菲律賓細胞生物學學會國際學術年會(2018)、第3屆亞洲藥學聯盟國際研討會(2017)等國內外重要學術會議上作大會報告。目前擔任中國藥學會海洋藥物專業委員會委員、浙江省藥學會海洋藥物專業委員會委員、寧波市“科技創新2025”重大專項生物醫藥領域專家組成員等學術兼職。
發表SCI論文79篇(其中第一作者/通訊作者論文45篇),包括本領域主流期刊J. Org. Chem., ACS Chem. Neurosci., J. Chromatogr. A, Front. Microbiol., Appl. Microbiol. Biotechnol. , Mar. Drugs, Harmful Algae, Int. J. Syst. Evol. Microbiol., 總影響因子大於250,他引1000次以上。
2000.09-2004.06浙江大學化學系本科
2004.09—2009.06浙江大學化學系博士
2009.07—2011.05美國華盛頓州立大學生物化學研究所博士后
主要研究方向:海洋藥用生物資源與創新藥物研究
(1)海洋藥物先導化合物發現。在國際上首次從30餘種海洋生物中發現新化合物123個,新骨架化合物8個。通過高通量活性篩選,獲得了3個抗阿爾茲海默症(AD)先導化合物,與寧波大學醫學院崔巍教授合作,首次報道了Eckmaxol和Fucoxanthin等抗AD先導化合物的作用機制(ACS Chem. Neurosci. 2018, 9, 1349−1356;Oxid. Med. Cell. Longev. 2017, 6792543;Mar. Drugs 2017, 15, 260)。此外,還發現了7個抗腫瘤(Harmful Algae 2016, 58, 66–73;Appl. Microbiol. Biotechnol. 2014, 98, 4369-4377;Mar. Drugs 2019, 17, 283)、5個抗菌(Front. Microbiol. 2019, 10, 2846;Mar. Drugs 2019, 17, 344; J. Antibiot. 2018, 71, 902-904)藥物先導化合物。為開發具有知識產權的新葯奠定了基礎。
(2)海洋天然產物高效製備新方法。針對“藍色葯庫”葯源瓶頸的高效製備關鍵技術難題,建立了Eckmaxol、Macrolactins等20餘種天然藥物先導化合物的高效分離純化新方法,取得了系列研究成果(J. Chromatogr. A 2013, 1272, 15-19;J. Sep. Sci. 2019, 42, 2510–2516;Mar. Drugs 2018, 16, 73)。實現了從粗提物到純化合物的一步式製備分離,回收率達到90%以上,高效製備方法的建立將加速海洋活性物質的新葯創製進程。
(3)海洋“難培養”微生物新資源挖掘。針對99%以上海洋微生物無法在實驗室常規條件下培養的關鍵技術難題,與Slava Epstein教授開展國際合作,首次改進和運用iChip、Diffusion Chamber等新型微生物原位培養技術深入挖掘海洋“難培養”微生物新資源,已發現新種378個,隨機培養的出新率達到50%以上,目前已完成並發表了其中8個海洋微生物新種的系統分類鑒定與基因組分析(Int. J. Syst. Evol. Microbiol. 2019, 69, 3293–3298; Int. J. Syst. Evol. Microbiol. 2018, 68, 2813-2818;Antonie van Leeuwenhoek 2018, 111, 1855–1862),從中發現了一系列新天然產物(Chem. Biodivers. In press,2020,中國藥學會海洋藥物專業委員會專刊),為突破海洋微生物資源瓶頸奠定了堅實基礎。
(4)海洋“中光層”生物新資源探索。作為我國首位下潛深度達到100米的國際認證科學潛水員,於2019年牽頭建立了國內首個海洋“中光層”(深度30-150米,占海洋生物多樣性80%以上)科學潛水團隊,率先在我國西沙群島和菲律賓Apo Reef(與菲律賓大學合作)等海域啟動了海洋“中光層”生物資源探索與系統挖掘工作,已採集中光層海綿、軟珊瑚、柳珊瑚等30餘種,設計運用新型微生物培養技術“連續流生物反應器”,實現了海綿共附生“難培養”微生物的實驗室高效培養,已發現微生物新種50餘個。探索和構建海洋“中光層”生物資源庫對我國海洋生物學研究具有戰略意義。
1. Weiyan Zhang, Can Chen, Ye Yuan, Dengquan Su, Lijian Ding, Slava S Epstein*, Shan He*. Pararhodobacter marinus sp. 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 Microbiology 2019, 69, 3293–3298.
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 Chemistry 2019, 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 Fungus Aspergillus niger Cultivated in Solid Medium. Marine Drugs 2019, 17, 344.
4徠. Xiaoping He, Lijian Ding*, Mengqi Yi, Jianzhou Xu, Xuezhen Zhou, Weiyang Zhang, Shan He*. Separation of five diketopiperazines from the marine fungus Alternaria alternate HK-25 by high-speed counter-current chromatography. Journal of Separation Science 2019, 42, 2510–2516.
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 fungus Aspergillus sp. LS45. Bioorganic & Medicinal Chemistry Letters 2019, 29, 1593–1596.
6. Lijian Ding*, Te Li, Xiaojian Liao, Shan He*, Shihai Xu*. Asperitaconic acids A–C, antibacterial itaconic acid derivatives produced by a marine-derived fungus of the genus Aspergillus. The Journal of Antibiotics 2018, 71, 902-904.
7. Weiyan Zhang, Ye Yuan, Dengquan Su, Lijian Ding, Xiaojun Yan, Min Wu, Slava S. Epstein*, Shan He*. Saccharospirillum mangrovi sp. nov., a bacterium isolated from mangrove sediment. International Journal of Systematic and Evolutionary Microbiology 2018, 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 from Ecklonia maxima, Produces Anti-β-amyloid Oligomer Neuroprotective Effects Possibly via Directly Acting on Glycogen Synthase Kinase 3β. ACS Chemical Neuroscience 2018, 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 Fungus Fusariumsp. LS68 by High-Speed Countercurrent Chromatography in Stepwise Elution Mode. Marine Drugs 2018, 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 Longevity 2017, 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 Fungus Trichoderma sp. HPQJ-34. Marine Drugs 2017, 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 in Karlodinium veneficum (strain GM2) from the East China Sea. Harmful Algae 2016, 58, 66–73.
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 Acetylcholinesterase in Vitro. Marine Drugs 2016, 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 Fungus Cladosporium sp. Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode. Marine Drugs 2015, 13, 354-365.
15. Lijian Ding, Shan He*, Xiaojun Yan*. Efficient preparation of pseudoalteromone A from marine Pseudoalteromonas rubra QD1-2 by combination of response surface methodology and high-speed counter-current chromatography: a comparison with high-performance liquid chromatography. Applied Microbiology and Biotechnology 2014, 98, 4369-4377.
16. Binbin Gu, Shan He*, Xiaojun Yan, Lixin Zhang*. Tentative biosynthetic pathways of some microbial diketopiperazines. Applied Microbiology and Biotechnology 2013, 97, 8439–8453.
17. Shan He*, Xiaojun Yan*. From Resveratrol to Its Derivatives: New Sources of Natural Antioxidant. Current Medicinal Chemistry 2013, 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 Bacterium Bacillus amyloliquefaciens using High-Speed Counter-Current Chromatography in Stepwise Elution Mode. Journal of Chromatography A 2013, 1272, 15-19.
19. Shan He, Liyan Jiang, Bin Wu, Chang Li, Yuanjiang Pan*. Chunganenol: An Unusual Antioxidative Resveratrol Hexamer from Vitis chunganensis. Journal of Organic Chemistry 2009, 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 Communications 2009, 379, 283–287.
21. Shan He, Yanbin Lu, Liyan Jiang, Bin Wu, Feiying Zhang, Yuanjiang Pan*. Preparative isolation and purification of antioxidative stilbene oligomers from Vitis chunganensis using high-speed counter-current chromatography in stepwise elution mode. Journal of Separation Science 2009, 32, 2339-2345.
22. Shan He, Bin Wu, Yuanjiang Pan*, Liyan Jiang. Stilbene Oligomers from Parthenocissus laetevirens: Isolation, Biomimetic Synthesis, Absolute Configuration and Implication of Antioxidative Defense System in the Plant. Journal of Organic Chemistry 2008, 73, 5233-5241.
23. Shan He, Cuirong Sun, Yuanjiang Pan*. Red Wine Polyphenols for Cancer Prevention. International Journal of Molecular Sciences 2008, 9, 842- 853.
24. Shan He, Yanbin Lu, Bin Wu, Yuanjiang Pan*. Isolation and purification of antioxidative isomeric polyphenols from the roots of Parthenocissus laetevirens by counter-current chromatography. Journal of Chromatography A 2007, 1151, 175- 179.
獲2012-2013年度寧波市優秀博士后榮譽稱號;
獲2018年寧波市科學技術獎二等獎(排名第一);
獲2019年浙江省自然科學獎二等獎(排名第一)。
1. 國家自然科學基金(NSFC)面上項目,基於iChip技術的海洋“未培養”微生物資源挖掘及新天然產物發現Resource mining of marine "uncultured" microbes by iChip and new natural products discovery(41776168),2018.01-2021.12
2. 國家自然科學基金(NSFC)青年項目,海洋Uncultured 放線菌資源挖掘及新天然產物發現Resource Mining of Marine Uncultured Actinomycetes and Discovery of New Natural Products(41306134),2014.01-2016.12
3. 國家外專局/教育部111計劃,海洋生物醫藥創新引智基地(D16013),2016.08-2021.08
4. 國家科技部(MOST)重點研發計劃項目子課題,深海多孔動物門藥物先導化合物的高效篩選與發現(2018YFC0310902),2018.08-2021.12
5. 國家科技部(MOST)星火計劃,褐藻多酚作為大黃魚飼料添加劑的應用與推廣(2013GA701024),2013.01-2014.12
6. 教育部(MOE)博士點基金,卡羅藻毒素高效製備及其在養殖水域中的快速檢測新方法研究(20133305120007),2014.01-2016.12
7. 浙江省自然科學基金(Zhejiang NSF),基於高速逆流色譜的卡羅藻毒素高效製備及新天然產物發現(LQ13B020004),2013.01-2015.12
8. 浙江省科技廳(Science Technology Department of Zhejiang Province)錢江人才計劃,通過氧化脅迫葡萄科植物產生新型抗腦卒中先導化合物的研究(2012R10068),2012.08-2013.12
9. 浙江省科技廳(Science Technology Department of Zhejiang Province)重點科技創新團隊子課題,海洋藍細菌中新型抗腫瘤藥物的開發(2012R10029-2),2011.04-2014.06
10. 寧波市科技局(Science Technology Department of Ningbo City)富民項目,海洋抗菌微生物產業化研究及其在大黃魚養殖中的應用示範(2017C10016),2017.01-2019.12
11. 寧波市自然科學基金(Ningbo NSF),白藜蘆醇低聚體生物合成誘導及聚合度與神經保護的構效研究(2013A610278),2013.02-2015.01
12. 寧波市海洋局(Marine Department of Ningbo City)海洋經濟創新發展示範項目,寧波海洋生物高值利用公共服務平台-寧波海洋微生物資源開發利用子平台(NBHY-2017-P2),2018.03-2020.12
13. 寧波市科技局(Science Technology Department of Ningbo City),寧波市海洋生物產業調研,2016.11-2017.06