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    刘波

    • 教授     博士生导师   硕士生导师
    • 性别:男
    • 毕业院校:上海交通大学
    • 学位:博士
    • 所在单位:基础医学院
    • 学科:生物医学工程. 生物物理学
    • 办公地点:厚坤楼C210
    • 联系方式:电话:0411-84706278 QQ:756200441
    • 电子邮箱:lbo@dlut.edu.cn

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    研究领域

    • 研究领域包括:

      1、机械应力在活细胞内定向物理传递调控细胞功能

              机械应力作用于细胞引起细胞功能改变的机制,绝大多数研究者认为是应力通过细胞膜上的离子通道、G蛋白偶联受体、整合素等途径直接转化为细胞内的化学信号进行调控。但这一观点却不能解释细胞在定向应力作用下的定向排列和迁移现象。本团队提出,机械应力在活细胞内的物理传递调控细胞定向迁移这一新的研究方向,即机械应力在细胞内部存在直接通过细胞骨架等成分进行物理传递,到达细胞远端应力集中的部位激活局部蛋白分子,从而调控细胞的极性变化。围绕这一研究方向,本团队将诺贝尔奖得主钱永健(Roger Y. Tsien)教授发明的荧光蛋白FRET技术融入该领域,通过活细胞荧光图像动态分析与处理,获得探针在细胞内的动态变化,如细胞内局部的蛋白活性变化与应力变化等等。其中自行设计制备活细胞动态检测RhoGDIαPIMPaxillin等蛋白活性的多个FRET探针,可在活细胞内动态观察检测这些蛋白的活性时空变化;研发了一系列检测活细胞内不同结构之间应力实时变化的FRET探针,并首次实现了活细胞的表面张力可视化检测,获光明日报、中国科学报、科学网、大连日报等多家主流媒体专门报道。此部分工作论文相继发表于Nature系列杂志Communications BiologyCell系列杂志iScience、国际毒理学会官方杂志Toxicological Sciences、生物物理领域Biophysical Journal、英国皇家学会Journal of Royal Society Interface、心血管领域Cardiovascular Research、生物材料领域Journal of Materials Chemistry B等杂志上。主持国家级项目5项,省部级项目4项。

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      2、疾病标志物早期检测微流控芯片

              目前临床的技术手段对于重大疾病标志物的诊断和检测有诸多缺点和不足,例如检测过程有创伤、成本高、特异性较低等,并且很难实现早期检测诊断。微流控芯片技术因其低消耗、集成化、高灵敏度等优势,逐渐成为未来临床检测载体的必然发展趋势。本团队以微流控芯片技术为依托,开发新型的用于恶性肿瘤检测的微流控芯片,针对癌细胞的生物力学、蛋白活性等特异性变化,采用病人尿液作为样品,结合生物力学细胞抓捕、环化荧光蛋白探针技术精确检测等手段,实现无创伤检测、大幅度降低检测成本,并能够实现早于临床病理诊断的早期检测,可用于家庭自检、医疗机构普查及医院精确诊断。已经完成五六种疾病标志物快速检测芯片的研发。主持大连市重点研发计划1项,企业横向项目4项,申报相关发明专利20余项,其中一项已经转让。

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      部分主持项目:

      1.        大连市重点科技研发计划项目 No. 2021YF18SN023 新型生物传感器技术及其在疾病快速检测中的应用研究 (高校部分) 200.0万元 进行中,主持

      2.        国家自然科学基金面上项目 No. 32071252 胞内应力传递调控血管内皮细胞极性变化的可视化研究 直接经费 58万,2021.01-2024.12 进行中,主持

      3.        国家自然科学基金面上项目No. 31670867  活细胞内机械应力传递的可视化研究 直接经费60, 2017.01-2020.12 已结题,主持

      4.        国家自然科学基金面上项目  No.10972139  基于共振能量转移技术的扰动流影响内皮细胞连接重建的力学生物学研究  2010.01-2012.12  43.00万元 已结题,主持

      5.        国家自然科学基金面上项目  No. 30570459  应力载荷脉动频率影响体外培养动脉重建的力学生物学研究   2006.01-2008.12  23.00万元  已结题,主持

      6.        国家自然科学基金青年基金项目 No. 30100060 脉动压力调控体外培养动脉重建的平滑肌细胞分化机制 2002.01~ 2004.12  19.00万元  已结题,主持

      7.        国家自然科学基金重点项目子课题 No. 10132020血管重建的生物力学研究20.00/150.002002.01~2005.12 已结题

      8.        国家自然科学基金重点项目子课题  No. 10732070 血管细胞分化与迁移的力学生物学机制 2008.01-2011.12  35.00/200.00 万元  已结题

       

      部分发表论文:

      1.  Cunli Wang, Shuai Shao, Na Li, Zhengyao Zhang, Hangyu Zhang and Bo Liu *. Advances in Alzheimer’s Disease-Associated Aβ Therapy Based on Peptide. International Journal of Mollecular Sciences. 2023, 24:13110. (JCR Q1 IF5.6)

      2.  Xianmeng Wang, Na Li, Zhengyao Zhang, Kairong Qin, Hangyu Zhang, Shuai Shao* and Bo Liu*. Visualization of Cell Membrane Tension Regulated by the Microfilaments as a “Shock Absorber” in Micropatterned Cells. Biology 2023, 12, 889. https://doi.org/10.3390/biology12060889 (JCR Q1 IF5.168)

      3. Cunli Wang, Yiming Yang, Xiaoyu Zhang, Zhenqiang Shi, Huiling Gao, Manli Zhong, Yonggang Fan, Hongyan Zhang, Bo Liu*, Guangyan Qing*, Secreted endogenous macrosomes reduce Aβ burden and ameliorate Alzheimer’s disease. Science Advances. 2023, DOI: 10.1126/sciadv.ade0293.

      4. Cunli Wang, Yiming Yang, Shuai Shao, Hangyu Zhang, Na Li, Zhengyao Zhang, Bo Liu*, Accurate detection of reactive oxygen species by tuning an elastic motif (GPGGA)4 in nanopores. Chemical Communication. 2023, 5929, 4368-4371.

      5.  Yuhang Jin, Aziz ur Rehman Aziz, Bin Wu, Ying Lv, Hangyu Zhang, Na Li, Bo Liu* and Zhengyao Zhang*. The road to unconventional detections: paper-based microfluidic chips. Micromachines 2022, 13, 1835. (JCR Q2 IF 3.523) WOS:000881330400001

      6.Manrong Qu, Kehui Yu, Aziz Ur Rehman Aziz, Hangyu Zhang, Zhengyao Zhang, Na Li*, Bo Liu*. The role of Actopaxin in tumor metastasis. Progress in Biophysics and Molecular Biology. 2022, 175:90-102 (JCR Q1 IF 4.799)

      7.Aziz ur Rehman Aziz, Sha Deng, Yuhang Jin, Na Li, Zhengyao Zhang, Xiaohui Yu *, Bo Liu*. The explorations of dynamic interactions of paxillin at the focal adhesions. BBA-Proteins and Proteomics. 2022, 1870(10):140825 doi.org: 10.1016/j.bbapap.2022.140825  (JCR Q2 IF 4.125)

      8.Jinxin Han, Hangyu Zhang, Na Li, Aziz Ur Rehman Aziz, Zhengyao Zhang*, Bo Liu*.  The raft cytoskeleton binding protein complexes personate functional regulators in cell behaviors. Acta Histochemica. 2022,124:151859.  doi.org:10.1016/j.acthis.2022.151859 (IF 2.147)

      9.Youyi Zhao, Aziz ur Rehman Aziz, Hangyu Zhang, Zhengyao Zhang, Na Li*,Bo Liu*. Review: A systematic review on active sites and functions of PIM-1 protein. Human Cell. 2022. 352):427-440 HUCE-D-21-00638R1IF4.374

      10. Shuai Shao, Sha Deng, Qingyun Jiang, Hangyu Zhang, Zhengyao Zhang, Na Li, Fengyu Cong, Timo Tiihonen, Bo Liu*.  A DNA-Encoded FRET Biosensor for Visualizing the Tension across Paxillin in Living Cells upon Shear Stress. Analysis & Sensing. 2022,2:e202100033 10.1002/anse.202100033 (欧洲化学姊妹刊)

      11. Gao TY, Zhang ZZ, Yang YN, Zhang HY, Li N*, Liu B*. Impact of RIM-BPs in neuronal vesicles release. Brain Research Bulletin, 2021; 170:129-136. doi: 10.1016/j.brainresbull.2021.02.012. Q2 IF3.37

      12. Qingyun Jiang#, Tingting Han#, Haijun Ren, Aziz Ur Rehman Aziz, Na Li, Hangyu Zhang, Zhengyao Zhang*, Bo Liu*. Bladder Cancer Hunting: A Microfluidic Paper-based Analytical Device. ELECTROPHORESIS. 2020. 4116-17):1509-151610.1002/elps.202000080. Q2 IF 2.754

      13. Tingting Han, Yuhang Jin, Chunyang Gen, Aziz ur Rehman Aziz, Yang Zhang, Sha Deng, Haijun Ren, Bo Liu*. Microfluidic Paper-based Analytical Devices in Clinical Applications. Chromatographia. 2020, 83693-701 DOI :10.1007/s10337-020-03892-1  (IF:1.552)

      14. Fei Xie, Shuai Shao, Baohong Zhang, Sha Deng, Aziz Ur Rehman Aziz, Xiaoling Liao, Bo Liu*. Differential phosphorylation regulates shear stress-induced polar activity of Rho-specific guanine nucleotide dissociation inhibitor α. Journal of Cellular Physiology. 2020, 2356978-6989 DOI: 10.1002/jcp.29594 (JCR Q1 IF:6.513)

      15. Peng Wang+, Chunyang Geng+, Lujun Pan*, Bo Liu*. Carbon Nanocoil Based Flexible Tip for Live Cell Study of Mechanotransduction and Electro-physiological Characteristics. Journal of Materials Chemistry B, 2020, 8, 1405 - 1410  DOI: 10.1039/C9TB02564B  (JCR Q1 7.571)

      16. Aziz ur Rehman Aziz, Xiaohui Yu, Qingyun Jiang, Youyi Zhao, Sha Deng, Kairong Qin, Hanqin Wang*, Bo Liu*. Doxorubicin-induced toxicity to 3D-cultured rat ovarian follicles on a microfluidic chip. Toxicology in Vitro. 2020, 62: 104677 (JCR Q2 IF:3.685)

      17. Aziz ur Rehman Aziz, Sumbal Farid, Kairong Qin, Hanqin Wang*, Bo Liu*. Regulation of insulin resistance and glucose metabolism by interaction of PIM kinases and insulin receptor substrates. Archives of Physiology and Biochemistry.  2020;1262):129-138 DOI: 10.1080/13813455. 2018. 1498903 (JCR Q2 IF 3.188)

      18. Wei Juan, Liu Chong, Jiang Yang, Duan Chunzheng, Chen Li, Li Wang, Liu Bo*, Li Jingmin*, Microfluidic device for generating regionalized concentration gradients under a stable and uniform fluid microenvironment. Journal of Micromechanics & Microengineering. 2019;29(1): 015008 (IF 2.282)

      19. Baohong Zhang, Fei Xie, Aziz ur Rehman Aziz , Shuai Shao, Wang Li, Sha Deng, Xiaoling Liao, Bo Liu*.Heat Shock Protein 27 Phosphorylation Regulates Tumor Cell Migration under Shear Stress. Biomolecules. 2019, 9, 50; doi:10.3390/biom9020050 (Q2 IF 6.064)

      20. Aziz ur Rehman Aziz, Chunyang Geng, Wang Li, Xiaohui Yu, Kai-Rong Qin, Hanqin Wang*, Bo Liu*. Doxorubicin induces ER calcium release via Src in rat ovarian follicles. Toxicological Sciences. 2019, 1681):171-178. doi: 10.1093/toxsci/kfy284  (JCR Q2 IF4.109国际毒理学会官方杂志)

      21. Shuai Shao, Xiaoling Liao, Fei Xie, Sha Deng, Xue Liu, Tapani Ristaniemi, Bo Liu*. FRET biosensor allows spatio-temporal observation of shear stress-induced polar RhoGDIα activation. Communications Biology, 2018, 1:224. DOI10.1038/s42003-018-0232-2  (JCR Q1 IF6.548 Nature系列期刊)

      22.  Wang Li, Xinlei Yu, Fei Xie, Baohong Zhang, Shuai Shao, Chunyang Geng, Aziz ur Rehman Aziz, Xiaoling Liao, Bo Liu*. A membrane-bound biosensor visualizes shear stress-induced inhomogeneous alteration of cell membrane tension. iScience, 2018, 7:180-190. DOI:10.1016/j.isci.2018.09.002 JCR Q1 IF6.107 Cell系列期刊)

      23.  Geng C+, Li C+, Li W, Yan W, Li J, Aziz A U R, Zhai X, Sun W*, Liu B*. A Simple Fabricated Microfluidic Chip for Urine Sample-based Bladder Cancer Detection. Journal of Micromechanics & Microengineering, 2018, 28: 115011. doi: 10.1088/1361-6439/aae016(IF 2.282)

      24.  Wang Li, Chunyang Gen, Bo Liu*. Visualization of synaptic vesicle dynamics with fluorescence proteins. Folia Neuropathologica, 2018; 56 (1): 21-29. DOI: 10.5114/fn.2018.74656 (IF2.494)

      25.  Wei Juan, Liu Chong, Jiang Yang, Liu Tao, Chen Li, Liu Bo*, Li Jingmin*. Uniform and stable supply of medium for in-vitro cell culture using a robust chamber. Journal of Micromechanics and Microengineering. 2018.  28(6) 065006· DOI: 10.1088/1361-6439/aab374  (IF 2.282)

      26. Aziz Ur Rehman Aziz, Sumbal farid, Kai-Rong Qin, Hanqin Wang*, Bo Liu*. PIM kinases and its relevance to the PI3K/AKT/mTOR pathway in regulation of ovarian cancer. Biomolecules. 2018, 8(1): 7; doi:10.3390/biom8010007  (Q2 IF 6.064)

      27. Chiyu Li, Wang Li, Chunyang Geng, Haijun Ren, Xiaohui Yu, Bo Liu*. Microfludic chip for cancer cell detection and diagnosis. Journal of Mechanics in Medicine and Biology. 2018, 18(1): 1830001. DOI: 10.1142/S0219519418300016

       

      2017年以前部分代表性论文

      1. Aziz Ur Rehman Aziz†, Mengjie Fu†, Jiu Deng, Chunyang Geng, Yong Luo, Bingcheng Lin, Xiaohui Yu*, and Bo Liu*, A Microfluidic Device for Culturing an Encapsulated Ovarian Follicle. Micromachines. 2017, 8(11), 335; doi:10.3390/mi8110335(JCR Q2 IF:3.523)

      2. Wenfeng Xu#Bo Liu#, Xue Liu, Jie Xu, Bo Li, Xiaoling Liao*. Regulation of BMP2-induced intracellular calcium increases in osteoblasts. Journal of Orthopaedic Research. 2016. 34(10):1725-1733. JOR-15-0392.R2 (23196)  (JCR Q2 IF 3.102)

      3. Liu, B. Shaoying Lu, Ying-li Hu, Xiaoling Liao, Mingxing Ouyang, Yingxiao Wang. RhoA and Membrane Fluidity Mediates the Spatially Polarized Src/FAK Activation in Response to Shear Stress. Scientific Reports. 201447008; DOI:10.1038/srep07008 (JCR Q2 IF 4.996)  

      4. Bo Liu, Shaoying Lu, Zonglai Jiang, Yingxiao Wang*. Two distinct phases of calcium signaling under flow. Cardiovascular Research, 2011, 91(1):124-133. (JCR Q1 IF 13.081)

      5. Bo Liu, Tae-Jin Kim, Yingxiao Wang. Live cell imaging of mechanotransduction. Journal of The Royal Society Interface, 2010, 7(S3): S365-375 (JCR Q2 IF 4.093)

      6.  Liu B, Qu MJ, Qin KR, Li H, Li ZK, Shen BR, Jiang ZL. Role of cyclic strain frequency in regulating the alignment of vascular smooth muscle cells in vitro. Biophysical Journal, 2008; 94(4):1497–1507. (JCR Q2 IF 3.699)

      7. Qu MJ*, Liu B*, Qi YX, Jiang ZL. Role of Rac and Rho-GDI Alpha in the frequency-dependent expression of h1-calponin in vascular smooth muscle cells under cyclic mechanical strain. Annals of Biomedical Engineering, 2008; 36(9): 1481–1488. (JCR Q2 IF 4.219)

       

      软件著作权:

      1、刘波,郝希龙.细胞图像中细胞骨架的识别分析软件。20220718受理,202210 14授权,登记号2022SR1403067

      发明专利:

      1、刘波,万雪,李娜,闫平平,张航与,张郑瑶,邵帅,一种胃泌素释放肽前体特异性结合短肽及用途;2023-05-31受理,专利申请号202310631437.4

      2、刘波,郭超,张航与,邵帅,张郑瑶,李娜;为细胞同时提供拉伸应力和基质硬度的耦合装置及其制备方法;2022-12-12受理,专利申请号 202211596705.5

      3、刘波,孙泽龙,张郑瑶,李娜,张航与. 一种基于FRET的活细胞内Paxillin蛋白活性检测生物探针及其重组质粒。20220928已受理,专利申请号202211187520.9

      4、刘波,赵璇竹,张航与,李娜,张郑瑶。一种细胞角蛋白19片段特异性结合短肽及用途 20220727受理,专利申请号 202210891378.x

      5刘波,赵璇竹,李娜,张航与,张郑瑶 一种神经元特异性烯醇化酶特异性结合短肽及用途 20220727受理,专利申请号 202210891392.x

      6刘波曲曼榕,李娜,张郑瑶,张航与。一种活细胞内连接微丝与局部黏着斑的生物应力传感器 20220321受理,专利申请号202210279705 .6

      7刘波,韩金鑫,张航与,李娜,张郑瑶一种检测活细胞细胞膜与骨架间应力传递的生物探针。20210527受理,专利申请号202110583124.7

      8刘波,姜清云,李娜,张郑瑶,张航与.一种检测间充质干细胞定向分化状态的生物探针。20210525受理,专利申请号202110568427.1

      9刘波,姜清云,李娜,张郑瑶,张航与.一种识别CD105的生物探针。20210525受理,专利申请号202110568429.0

      10刘波,王贤萌一种利用PDMS图章精准控制单个细胞形状的方法。20190926受理,专利申请号201910921374X

      11刘波韩亭亭,耿春阳一种多指标联合检测标志性蛋白纸芯片。20190118受理,专利申请号201910048051.4

      12刘波金禹航.一种纸芯片通用通道结构及其制备方法。20210420授权,专利号201910509971.1

      13刘波,耿春阳一种用于细胞高效抓捕的新型微流控阵列。 20210820授权,专利号20180823719.3

      14刘波,邓莎一种检测活细胞内Paxillin蛋白力传递的荧光生物探针。20200814授权,专利号ZL 201711274845.X

      15刘波,李旺,于新磊,张树利,孙坚原一种基于FRET技术检测细胞膜表面张力的生物探针。2019.04.01授权,专利号 201610752206.9

      16刘波,邵帅,谢飞一种检测细胞内RhoGDIa活性动态变化的FRET探针。2019.01.01授权,专利号201610150171.1

      17刘波,翟晓峰. 快速检测膀胱癌三种亚型的微流控芯片及其制造和使用方法。2019.06.04授权 专利号201610980328.

      18刘波,翟晓峰.一种微流控芯片。 2018.09.25 授权 专利号201610980781.4

      19刘波,刘晓光,于新磊两种不同单细胞之间相互作用的微流控芯片装置,2016.06授权,专利号ZL201410466404.X

      20刘波,李驰宇,李旺,耿春阳,辛嘉龙一种可以同时检测尿液中膀胱癌细胞、结石、血细胞和细菌的微流控芯片,2016.08授权,专利号ZL201510263042.9