生物芯片与药物开发

§1. 中药功能研究与方剂开发 Functional Study of Traditional Chinese Medicine and Formulae Development

中医药是中华民族的珍贵宝藏。我们利用高通量测序技术,检测了数千个中药及天然产物作用于不同细胞系后的特征基因表达情况,形成分子版“本草纲目”,针对重大疾病(代谢性疾病、心血管疾病、传染性疾病和癌症等),筛选出一系列候选的中药及天然产物,如老鹰茶、烟管头草等,并对其进行系统的功能研究,努力实践“中医西释”。在此基础上,通过大数据挖掘、人工智能等方法,开发出可改善疾病相关信号通路的候选中药方剂,并开展体、内外功效验证及临床试验,旨在开发出药效明确、作用机制清晰、安全可靠的中药方剂,助力中医药的科学化和工程化。

药物开发1-1药物开发1-2 

  • *Qiao, L., Huang, W., Zhang, X., Guo, H., Wang, D., Feng, Q., Jin, R., Xie, L., Li, W., and Cheng, J. (2021). “Evaluation of the immunomodulatory effects of anti-COVID-19 TCM formulae by multiple virus-related pathways” Signal Transduction and Targeted Therapy, Feb 4;6(1):50.
  • *Feng, J., Yang, J., Chang, Y., Qiao, L., Dang, H., Luo, K., Guo, H., An, Y., Ma, C., Shao, H., Tian, J., Yuan, Y., Xie, L., Xing, W., Cheng, J. (2019). “Caffeine-free hawk tea lowers cholesterol by reducing free cholesterol uptake and the production of very-low-density lipoprotein” Communications Biology, May 8;2:173.
  • *Dang, H., Li, H., Ma, C., Wang, Y., Tian, J., Deng, L., Wang, D., Jing, X., Luo, K., Xing, W., Cheng, J., Guo, H., Xie, L. (2019). “Identification of Carpesium cernuum extract as a tumor migration inhibitor based on its biological response profiling in breast cancer cells” Phytomedicine, Nov;64:1530c72.
  • *谢兰, 郭弘妍, 邢婉丽, 程京, 党红蕾. 荻的新用途及一种抗肿瘤药物. 专利授权号:ZL201710526965.8
  • *谢兰,王栋,张卫东,孙义民,安燕南,邵伟,李慧梁,郭弘妍,李莎莎,邢婉丽,程京。童子益母草的新用途。专利授权号:ZL201610806231.0

 

§2.细胞操作芯片 Chips for Cell Manipulation

药物开发需要高通量的细胞培养与操作平台,我们成功开发了一款阵列式微坑细胞培养芯片。该芯片表面具有一层超疏水聚合物,可以将每一个微坑彻底隔绝开来,实现对细胞培养微环境的独立控制。该芯片具有操作简便、通量高等多种优势,并且可以在芯片上实现对细胞的培养、转染和染色分析等操作。
细胞电穿孔是一种通过脉冲电场作用使细胞膜表面形成可恢复的微孔从而将外源物质(质粒、RNA、蛋白、药物等)导入细胞的一项技术,具有转染效率高、无细胞毒性、成本低等优点。我们成功开发了一系列用于贴壁和悬浮细胞转染的电穿孔芯片和装置,为基因功能研究、药物开发提供高效、高通量的转染工具。

药物开发2

  • *Zhou, Y., Lu, Y., Cheng, J. and Xu, Y.  (2020)  "Highly uniform in-situ cell electrotransfection of adherent cultures using grouped interdigitated electrodes" Bioelectrochemistry, 132:107435.
    Bian, S., Zhou,Y., Hu, Y., Cheng, J., Chen, X., Xu, Y. and Liu, P.  (2017) “High-throughput in situ cellelectroporation microsystem for parallel delivery of single guide RNAs into mammalian cells.” Scientific Reports, 7: 42512.
  • *Zhang, P., Zhang, J., Bian, S., Chen, Z., Hu, Y., Hu, R., Li, J., Cheng, Y., Zhang, X., Zhou, Y., Chen, X. and Liu, P.  (2016) “High-throughput superhydrophobic microwell arrays for investigating multifactorial stem cell niches.” Lab on a Chip, 16: 2996-3006. Xu, Y., Su, S., Zhou, C., Lu, Y. and Xing, W. (2015) “Cell electroporation with a three-dimensional microelectrode array on a printed circuit board” Bioelectrochemistry, 102: 35-41.