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韩兵男 课题组组长 教授 博导    

韩兵男，教授，博导，浙江省特聘专家、省级领军人才。历任中国海洋湖沼学会海洋生物技术分会常务理事、中国生物化学与分子生物学会生物技术专委会委员、浙江省药学会海洋药物专委会委员、TOXINS等国际期刊编委。研究方向聚焦于天然药物和生物医学材料，作为第一或通讯作者在Chemical Engineering Journal、Materials & Design、Organic letters、European Journal of Medicinal Chemistry、Journal of Organic Chemistry、Analytical Chemistry等重要期刊发表多篇学术论文。本课题组国际上首次发现海洋蓝细菌次生代谢物Aplysiatoxin具有钾离子通道选择性抑制作用，该工作近期被国际著名期刊Natural Product Reports （Issue 2, 2023）选为32篇国际天然产物热点文章之一（Hot off the press）。团队于2021年与国家级专精特新“小巨人”企业浙大迪迅生物基因工程有限公司成立了浙江理工-迪迅抗过敏联合研究中心。主持完成多项863计划、国家自然科学基金和浙江省自然科学基金项目。获得了2021年度浙江省海洋科学技术进步奖三等奖。


一、高等教育：

2000/09 – 2005/06，美国俄勒冈州立大学(Oregon State University)，药学院，海洋天然产物及药物化学，博士

 导师：William H. Gerwick 教授

 课题：海洋蓝藻的抗癌次生代谢物的化学研究

 博士期间做过3年助教工作

1996/10 –1999/12,   美国加州州立大学(California State University, Northridge)，有机化学，硕士

硕士期间作为助教老师带过3年本科生实验课

1990/09 – 1994/06，杭州大学，生物化学与微生物学，本科

二、工作简历

2017/01 – 至今，浙江理工大学生命科学学院，研究员，特聘教授

2013/03 – 2016/12, 上海交通大学医学院附属仁济医院，海洋药物研究中心，

研究员

2010/10 – 2013/02, 浙江大学，海洋科学与工程学系, 副研究员

2010/10 – 2012/07, 美国普渡大学，药学院，访问教授（visiting assistant professor）

2008/03 – 2010/05, 美国国立癌症研究院(NCI), 研究员（research scientist）

2007/10 – 2008/02, 美国普渡大学，药学院，资深博士后（senior postdoctor）

2005/07 – 2007/09, 美国俄勒冈州立大学，质谱分析中心, 博士后



三、主持和主要参与的国内外研究项目：

1） 国家自然科学基金医学部海洋药物面上项目“基于Aplysiatoxin衍生物的钾离子通道Kv1.5抑制剂的发现及作用机制研究”，项目编号：8197130705（主持，2020/01-2023/12）

2） 浙江省公益技术研究计划“基于解脂耶氏酵母脂肪酶Lip2的鲈鱼饲料添加剂的开发与应用”，项目编号：LGN18C190011（主持，2018/01-2020/12）

3） 国家863计划海洋生物资源利用技术领域课题“饲料用海洋脂肪酶-单细胞蛋白联产关键技术及产品”,项目编号：2014AA093510（主持，2014/01-2016/12）

4） 国家自然科学基金医学部海洋药物面上项目“基于Keap1-Nrf2-ARE信号通路的活性先导化合物的发现及作用机制研究”,*项目

：/81373321（主持，2014/01-2017/12）

5） 国家863计划课题“深海微生物分离培养与基因资源获取技术研究”,项目编号：2012AA092103（骨干，2012/01-2015/12）

6） 浙江省自然科学基金“浙江近海半丰满鞘丝藻的抗癌活性物质筛选、分离及结构分析”，（Y2100044）（主持, 2010-2012）

7） 浙江大学科研青年专项“浙江近海海洋蓝藻的抗癌活性物质筛选、分离及结构分析”（2010QNA4014）（主持，2010-2012）

8） 项目：Mitochondrial Proteomics of the Aging Heart（2007）资助: 美国国立卫生研究院（NIH）重大项目; 5R01AG025372-03（主要参与）

9） 项目：Neurotoxins from Marine Algae and Cyanobacteria（2007）资助: 美国国立卫生研究院（NIH）重大项目; 5R01NS053398-07 （主要参与）

10）项目：Lipidomic profile of endocannabinoids from neuronal cells（2011）资助: 美国国立卫生研究院（NIH）项目; R21DA024193  （主要参与）

 

 

四、近年发表论文：

  1. Zhang S, Liu Y, Javeed A, Jian C, Sun J, Wu S, Han B. Treatment of allergy: Overview of synthetic anti-allergy small molecules in medicinal chemistry. Eur J Med Chem. 2023 Jan 27;249:115151. doi: 10.1016/j.ejmech.2023.115151
  2. Qin Y, Li J, Kuang J, Shen S, Jiang J, Zhang Z, Zhao C, Zhou X, Huang B* and Han B* (2022) Sensitive time-resolved                      fluoroimmunoassay for the quantitative detection of okadaic acid. Front. Mar. Sci. 9:961751. Doi: 10.3389/fmars.2022.961751 
  3.  Chen W, Ye K, Zhu X, Zhang H, Si R, Chen J, Chen Z, Song K, Yu Z, Han B*. Actinomycin X2, an Antimicrobial                             Depsipeptide from Marine-Derived Streptomyces cyaneofuscatus Applied as a Good Natural Dye for Silk Fabric. Marine Drugs.   2022; 20(1):16. https://doi.org/10.3390/md20010016
  4.  Shen SC, Wang WP, Chen ZJ, Zhang HH, Yang YC, Wang XL, Fu P*, Han BN*. Absolute Structure Determination and Kv1.5 Ion Channel Inhibition Activities of New Debromoaplysiatoxin Analogues. Marine Drugs. 2021; 19(11):630. https://doi.org/10.3390/md19110630
  5. Chen JN, Xu L, Zhou YR, Han BN*. Natural Products from Actinomycetes Associated with Marine Organisms. Marine Drugs. 2021; 19(11):629. https://doi.org/10.3390/md19110629
  6.  Zhang HH, Zhang XK, Si RR, Shen SC, Liang TT, Fan TT, Chen W, Xu LH*, Han BN*. Chemical and Biological Study of Novel Aplysiatoxin Derivatives from the Marine Cyanobacterium Lyngbya sp. Toxins (Basel). 2020 Nov 23;12(11):E733. doi: 10.3390/toxins12110733. PMID: 3323839
  7. Meilin Zhu  Zhen Yang , Haotian Wang , Qi Gan , Guojian Zhang  , Qian Che , Tianjiao Zhu , Qianqun Gu , Bingnan Han* , Dehai Li* .Penispirozines A-H, Three Classes of Dioxopiperazine Alkaloids with Spirocyclic Skeletons Isolated from the Mangrove-Derived Penicillium janthinellum [published online ahead of print, 2020 Aug 20]. J Nat Prod. 2020;10.1021/acs.jnatprod.0c00451. doi:10.1021/acs.jnatprod.0c00451
  8. Xu, L., Ye, K. X., Dai, W. H., Sun, C., Xu, L. H., & Han, B. N*. (2019). Comparative Genomic Insights into Secondary Metabolism Biosynthetic Gene Cluster Distributions of Marine Streptomyces. Mar Drugs, 17(9). doi:10.3390/md170904982.      
  9. Ting-Ting Fan, Hui-Hui Zhang, Yang-Hua Tang, Fan-Zhong Zhang, Bing-Nan Han *. Two New Neo-debromoaplysiatoxins—a Pair of Stereoisomers Exhibiting Potent Kv1.5 Ion Channel Inhibition Activities. Marine Drugs, 2019, 17(12): 652.
  10.  Tang Y-H, Liang T-T, Fan T-T, Keen L J, Zhang X-D, Xu L, Zhao Q, Zeng R, Han B-N*. Neo-debromoaplysiatoxin C, with new structural rearrangement, derived from debromoaplysiatoxin. Nat. Prod. Res. 2019, DOI: 10.1080/14786419.2019.1577840.
  11. Tang Y-H, Wu J, Fan T-T, Zhang H-H, Gong X-X, Cao Z-Y, Zhang J, Lin H-W, Han B-N*. Chemical and biological study of aplysiatoxin derivatives showing inhibition of potassium channel Kv1.5. RSC Advances. 2019, 9, 7594 - 7600.
  12. Kai‐Xiong Ye,Ting‐Ting Fan,Lawrence Jordan Keen,Bing‐Nan Han. A Review of Pigments Derived from Marine Natural Products[J]. Israel Journal of Chemistry,2019,59(5).
  13. Han B-N*, Liang T-T, Keen L J, Fan T-T, Zhang X-D, Xu L, Zhao Q, Wang S-P, Lin H-W. Two Marine Cyanobacterial Aplysiatoxin Polyketides, Neo-debromoaplysiatoxin A and B, with K+ Channel Inhibition Activity. Org. Lett. 2018, 20: 578-581.
  14. Liang T T, Zhao Q, He S, et al. Modeling Analysis of Potential Target of Dolastatin 16 by Computational Virtual Screening.[J]. Chemical & Pharmaceutical Bulletin, 2018, 66(6):602-607.
  15. Wang Y, Yan J, Zhang X, et al. Tolerance properties and growth performance assessment of Yarrowia lipolytic lipase in brolers[J]. Journal of Applied Animal Research, 2017:1-6.
  16. Jinyong Yan *, Bingnan Han（共同第一）, Li Xu, Yunjun Yan, Genhan Zha, Dujie Pan, Liangcheng Jiao, Yaofeng Wang, Catherine Madzak. A promising feed Yarrowia lipolytica yeast: homologous overexpression of feed enzyme lipase, and simultaneous production of feed yeast biomass. Scientific Reports， 2018，8:758
  17. Li Liu,Wei Wu,Jing Li,Wei-Hua Jiao,Li-Yun Liu,Jie Tang,Lei Liu,Fan Sun,Bing-Nan Han,Hou-Wen Lin. Two sesquiterpene aminoquinones protect against oxidative injury in HaCaT keratinocytes via activation of AMPKα/ERK-Nrf2/ARE/HO-1 signaling[J]. Biomedicine & Pharmacotherapy,2018,100.
  18. Dezhi Li, Bingnan Han, Rui Wei,el. N-terminal α-amino group modification of antibodies using a site-selective click chemistry method[J]. Mabs, 2018:00-00.
  19. Liu, Li，Wu, Wei，Li, Jing，Jiao, Wei-Hua，Liu, Li-Yun，Tang, Jie，Liu, Lei，Sun, Fan(*)，Han, Bing-Nan *，Lin, Hou-Wen(*),Two sesquiterpene aminoquinones protect against oxidative injury in HaCaT keratinocytes via activation of AMPKα/ERK-Nrf2/ARE/HO-1 signaling, Biomedicine & Pharmacotherapy, 2018.2.22,100: 417-425
  20. Meilin Zhu, Zhen Yang, Huimin Feng, Qi Gan, Qian Che, Tianjiao Zhu, Qianqun Gu, Bingnan Han * and Dehai Li *. Trichodermamides D–F, heterocyclic dipeptides with a highly functionalized 1,2-oxazadecaline core isolated from the endophytic fungus Penicillium janthinellum HDN13-309. RSC Advances. 2017, 7, 48019–48024.
  21. Zhen Yang, Mei-lin Zhu, De-hai Li*, Rong Zeng *, Bing-nan Han *. N-Me-trichodermamide B isolated from Penicillium janthinellum, with antioxidant properties through Nrf2-mediated signaling pathway. Bioorg. Medi. Chem. 31 Oct 2017, 25(24):6614-6622
  22. Qiu-Ye Chai, Zhen Yang, Hou-Wen Lin,* and Bing-Nan Han*. Alkynyl-Containing Peptides of Marine Origin: A Review  Mar. Drugs 2016, 14, 216; doi:10.3390
  23. Jian-Hong Gan, Wen-Zhen Hu, Hao-Bing Yu, Fan-Yang, Meng-Xue Cao, Hua-Jin Shi, Yong-Feng Kang* and Bing-Nan Han*. Three New Aaptamine Derivatives   from the South China Sea Sponge Aaptos aaptos.  J. Asian Natural Products Research; 2015 17(12), 1231-1238
  24. Kai-Xuan Zhan, Wei-Hua Jiao, Fan Yang, Jing Li, Shu-Ping Wang, Yu-Shan Li,Bing-Nan Han,*（共同通讯） and Hou-Wen Lin *. Reniochalistatins A–E, Cyclic Peptides from the Marine Sponge Reniochalina stalagmitis. J. Nat. Prod. ; 2014, 77 (12), pp 2678–2684
  25. Shu-Juan Piao, Wei-Hua Jiao, Fan Yang, Yang-Hua Yi, Ying-Tong Di, Bing-Nan Han,*（共同通讯） and Hou-Wen Lin *. New Hippolide Derivatives, withProtein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity from the Marine Sponge Hippospongia lachne. Mar. Drugs; 2014, 12(7), 4096-4109
  26. Shu-Juan Piao,Yun-Long Song,Wei-Hua Jiao,Fan Yang,§ Xiang-Fang Liu, Wan-Sheng Chen, Bing-Nan Han*（共同通讯）, and Hou-Wen Lin*. Hippolachnin A, a New Antifungal Polyketide from the South China Sea Sponge Hippospongia lachne.Org. Lett.；15 (14), 3526–3529，2013
  27. 26.   Bingnan Han*, Rachel Wright, Yi Fang, Aaron Kirchoff, Vincent jo Davisson, Julia Chester and Eric Barker . Quantitative LC–MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor. Analytical Biochemistry; 432(2),74-81，2013
  28. Bingnan Han, Mike Hare and Claudia S. Maier. A differential “Bottom Up” proteomic strategy for the site-specific identification and quantitation of endogenous oxylipid protein modifications. Journal of proteomics ；75(18)，5724-5733, 2012
  29. Bingnan Han, Luke H. Stockwin, Chad Hancock, Sherry X. Yu, Melinda G. Hollingshead, and Dianne L. Newton. Proteomic Analysis of Nuclei isolated from cancer cell lines treated with Indenoisoquinoline NSC724998, a novel Top1 inhibitor. Journal of Proteome Research; 9(8), 4016-4027, 2010
  30. Bingnan Han*, Harald Gross, Kerry L. McPhail, Doug Goeger, Claudia S. Maier,William H. Gerwick. Wewakamide A and guineamide G, cyclic depsipeptides from the marine cyanobacteria Lyngbya semiplena and Lyngbya majuscula. Journal of Microbiology and Biotechnology(IF: 1.4); 21(9)，930-936, 2012
  31. 30.  Bingnan Han, Uwe M. Reinscheid, William H. Gerwick, Harald Gross. The structure elucidation of isomalyngamide K from the marine cyanobacterium Lyngbya majuscula by experimental and DFT computational methods. Journal of Molecular structure(IF: 1.7); 989, 109-113, 2011
  32. Chad N. Hancock,Luke H. Stockwin, Bingnan Han, Raymond D. Divelbiss, Jung Ho Jun, Sajay V Malhotra, Melinda G. Hollingshead and Dianne L. Newton. A copper chelate of thiosemicarbazone NSC689534 induces Oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radical Biology and Medicine(IF: 5.8); 50(1)，110-21, 2011
  33. Saini V, Hose CD, Monks A, Nagashima K, Han B, Newton DL, Millione A, Shah J, Hollingshead MG, Hite KM, Burkett MW, Delosh RM, Silvers TE, Scudiero DA, Shoemaker RH. Identification of CBX3 and ABCA5 as Putative Biomarkers for Tumor Stem Cells in Osteosarcoma. PLoS One(IF: 4.1); 7(8)，e41401, 2012
  34. Luke H. Stockwin, Bingnan Han, Maja A. Bumke, Sherry X. Yu, Melinda G. Hollingshead, Mahmoud A. ElSohly, Waseem Gul, Desmond Slade, Ahmed Galal, and Dianne L. Newton. Artemisinin dimeranti-cancer activity is mediated by heme-catalyzed ROS generation and ER stress Induction.International Journal of Cancer(IF: 5.4); 125(6), 1266-1275, 2009
  35. Bingnan Han, Fred Stevens and Claudia S. Maier.  Design, Synthesis, and Application of a Hydrazide-Functionalized Isotope-Coded Affinity Tag (HICAT) for the Quantification of Oxylid Protein Conjugates. Anal. Chem.(IF: 5.8); 2007; 79(9); 3342-3354.
  36. 35.  Juan Chavez, Jianyong Wu, Bingnan Han, Woon-Gye Chung, and Claudia S. Maier.  New Role for an Old Probe: Affinity Labeling of Oxylipid Protein Conjugates by N’-Aminooxymethylcarbonylhydrdrazino-D-biotin.  Anal. Chem.78 (19), 6847 -6854, 2006.
  37. Ramaswamy AV, Flatt PM, Edwards DJ, Simmons TL, Han B and Gerwick WH. The secondary metabolites and biosynthetic geneclusters of marine cyanobacteria. Applications in biotechnology. Frontiers in Marine Biotechnology  (2006), 175-224.
  38. Bingnan Han, Harald Gross, Douglas E. Goeger, Susan L. Mooberry, and William H. Gerwick. Aurilides B and C, Cancer Cell Toxins from a Papua New Guinea Collection of the Marine Cyanobacterium Lyngbya majuscule. J. Nat. Prod.  2006, 69, 572-575.
  39. Bingnan Han, Kerry L. McPhail, Harald Gross, Doug Goeger, Susan    Mooberry, and William H. Gerwick. Isolation and Structure of Five Lyngbyabellin Derivatives from a Papua New Guinea Collection of the Marine Cyanobacterium Lyngbya majuscule. Tetrahedron, 2005, 61, 11723-11729.
  40. Bingnan Han, Doug Goeger, Claudia S. Maier, and William H. Gerwick. The Wewakpeptins, Cyclic Depsipeptides from a Papua New Guinea Collection of the Marine Cyanobacterium Lyngbyasemiplena. J. Org. Chem. , 2005, 70 (8), 3133
  41. Bingnan Han, Kerry L. McPhail, Alessia Ligresti, Vincenzo Di Marzo, and William H. Gerwick. Semiplenamides A-G, Fatty Acid Amides from a Papua New Guinea Collection of the Marine Cyanobacterium Lyngabya semiplena. J. Nat. Prod., 2003, 66, 1364-1368.
  42. Hao-Bing Yu, Yang Fan, Sun Fan, Guo-Yi Ma, Jian-Hong Gan, Wen-Zhen Hu, Bing-Nan Han, Wei-Hua Jiao, and Hou-Wen Lin. Cytotoxic aaptamine derivatives from the South China Sea sponge Aaptos aaptos.Journal of Natural Products, 77(9), pp 2124-2129, 2014/9/26.
  43. Yang Fan, Yike Zou, Ru-Ping Wang, Hamann Mark T, Hong-Jun Zhang, Wei-Hua Jiao, Bing-Nan Han, Shao-Jiang Song, and Hou-Wen Lin. Relative and absolute stereochemistry ofdiacarperoxides: antimalarial norditerpene endoperoxides from marine sponge Diacarnus megaspinorhabdosa.Marine Drugs, 12(8), pp 4399-4416, 2014/8.
  44. Wei-Hua Jiao, Ting-Ting Xu, Hao-Bing Yu, Guo-Dong Chen, Xiao-Jun Huang, Yang Fan, Yu-Shan Li, Bing-Nan Han, Xiao-Yan Liu, and Hou-Wen Lin. Dysideanones A-C, Unusual Sesquiterpene Quinones from the South China Sea Sponge Dysidea avara. Journal of Natural Products, 77(2), pp 346-350, 2014/2.
  45. Wei-Hua Jiao, Ting-Ting Xu, Hao-Bing Yu, Feng-Rong Mu, Jia Li, Yu-Shan Li, Fan Yang, Bing-Nan Han, and Hou-Wen Lin. Dysidaminones A–M, cytotoxic and NF-kB inhibitory sesquiterpene aminoquinones from the South China Sea sponge Dysidea fragilis.RSC Advances, 4(18), pp 9236-9246, 2014/1/20.
  46. Wei-Hua Jiao, Li Jing, Liu Qian, Ting-Ting Xu, Guo-Hua Shi, Hao-Bing Yu, Yang Fan, Bing-Nan Han, Li Min, and Hou-Wen Lin. Dysidinoid A, an Unusual Meroterpenoid with Anti-MRSA Activity from the South China Sea Sponge Dysidea sp.Molecules, 19(11), pp 18025-18032, 2014.
  47. Yan Min, Zhu Yan, Hong-Jun Zhang, Wei-Hua Jiao, Bing-Nan Han, Zhao-Xi Liu, Qiu Feng, Wan-Sheng Chen, and Hou-Wen Lin. Anti-inflammatory secondary metabolites from the leaves of Rosa laevigata. BIOORGANIC & MEDICINAL CHEMISTRY, 21(11), pp 3290-3297, 2013

 

五、发明专利：

1. 韩兵男，司冉冉，陈佳宁. 一种抗菌丝素蛋白及其制备方法（申请号 202110359748.0）

2. 韩兵男，叶凯雄，张凡忠，余志成，宋凯利，严昕悦. 一种放线菌素的应用（授权号 CN 110983816 B) 

3. 阎金勇, 韩兵男, 徐莉, 闫云君. 一种转化解脂耶氏酵母及其构建方法与应用（授权号 CN 106754446B）

4. 张大伟, 王政，韩兵男. 一种高稳定性脂肪酶的发酵工艺及其提高稳定性的方法（申请号201611115245.4）

5. 韩兵男，杨珍，曾嵘，李德海，朱美林，梁婷婷, 一种生物碱类化合物及抗氧化的应用（授权号 CN 107501249B）

6. 韩兵男，梁婷婷，郑玲辉,一种聚酮类化合物及其制备方法和应用（授权号 CN 107602580 B）

  7. 韩兵男，樊婷婷，梁婷婷，唐杨华，张慧慧，龚晓霞，一种蓝藻Lyngbya majuscula 中的提取物及提取方法和应用（授权号：CN 109265432 B）

8. 韩兵男，樊婷婷，张慧慧，龚晓霞,唐杨华，梁婷婷,一种新骨架结构的Aplysiatoxin衍生物及其应用（授权号 CN 110627803B）