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生物与医学前沿论坛(二)

  报告时间:2019年6月10日(周一)9:30

  报告地点:北辰校区生物物理研究所108会议室

 

  报告题目(一):Finding New Anti-Arrhythmic Drugs

  报告嘉宾:Jianmin Cui 

 

  报告简介:KCNQ1 is a voltage activated potassium channel. It is important for the function of various tissues including cardiac muscle and epithelium. Tissue-specific beta subunits modulate KCNQ1 function with drastically different phenotypes to suit the physiological role of the channel in various tissue types, but the underlying mechanism was not clear. This talk will show structural and functional data that reveal two open states of the KCNQ1 channel that have different properties. Different beta subunits selectively and differentially modulate the two open states, giving rise to various phenotypes.  To further illustrate the functional importance of KCNQ1 in cardiac function, we screened a chemical library  in silico  by docking compounds to the voltage sensing domain of the channel, and investigated a hit compound that enhanced the currents in subsequent electrophysiological experiments. The compound terminated lethal ventricular tachyarrhythmias with high efficacy in various animal models and different species. On the other hand, the compound at the same dosage did not cause significant changes of the control ECG in the whole hearts. These results suggest that KCNQ1 is a target for antiarrhythmic therapy, and its activators have promise as novel antiarrhythmic drugs.

  嘉宾简介:Jianmin Cui is Professor on the Spencer T. Olin Endowment at Washington University in St. Louis, in the Department of Biomedical Engineering. He received Ph.D. in Physiology and Biophysics from State University of New York at Stony Brook and a post-doctoral training at Stanford University. He was an assistant professor of Biomedical Engineering at Case Western Reserve University before moving to St. Louis in 2004. His research interests are on membrane permeation to ions, drugs and genes, including 1) molecular mechanisms of ion channel function, molecular/cellular mechanism of disease-associated ion channel mutations, and small molecules that modulate ion channel function; and 2) ultrasound-mediated ion channel activation and drug/gene delivery.  Prof. Cui received Established Investigator Award from the American Heart Association and is a fellow of the American Institute for Medical and Biological Engineering (AIMBE).

 

  报告题目(二):Targeted genome modification in plants using CRISPR/Cas9

  报告嘉宾:李君

  嘉宾简介:李君,首都师范大学博士后,主要从事(1)植物基因组编辑技术及新方法的开发利用。首次将CRISPR/Cas9技术应用于植物中进行植物基因组编辑;在水稻中建立了一种高效的基因定点替换及插入的基因组编辑体系;利用CRISPR/Cas9技术在玉米中创制了TMS5突变体,表现温敏雄性不育的表型;利用CRISPR/Cas9技术对拟南芥基因组进行定点编辑;(2)基因表达调控在植物发育和适应环境中的作用和机制。以模式植物拟南芥为材料,主要采用遗传学、细胞生物学、分子生物学以及生物化学等技术手段研究基因表达调控植物发育和适应环境的分子机制。

  迄今为止以第一作者或共同第一作者在Nature Biotechnology (2013), Nature Plants (2016), Journal of Genetics and Genomics (2017), Small Methods (2019)等具有国际影响力的学术期刊上发表多篇论文。

 

  报告题目(三):Drug screening targeting at TMEM16A/CaCCs and dual-target antitumor strategy based on pH sensitive nanoparticles

  报告嘉宾:安海龙

  报告简介:Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Transmembrane protein 16A (TMEM16A) has been confirmed as the molecular counterpart of CaCCs which greatly pushes the molecular insights of CaCCs forward. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. Here, the authors identified two modulators from the traditional Chinese medicine, an activator, Ginsenoside Rb1 (GRb1) which can directly activate the channel, increase the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo and may serve as a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction, an inhibitor, matrine which can dramatically inhibit the growth of lung adenocarcinoma tumors in xenografted mice. Our data indicates that TMEM16A may serve as a novel antitumor drug target for lung adenocarcinoma.

  The nanoparticle delivery systems accomplish targeted drug delivery, controlled drug release, enhancing the efficacy and reducing the side effects. Here, the authors actualized a novel dual-targeting antitumor strategy via pH sensitive nanoparticle loading with TMEM16A inhibitors. Our data show that an inhibitor of TMEM16A can suppress the proliferation and migration of lung adenocarcinoma in vitro and the growth of the tumor in vivo. Then, we designed a pH-sensitive nanoparticle, PEO-b-P (DMAEMA -co-MAEBA), targeting to the acidic environment of lung adenocarcinoma tissues. The results showed that "dual-targeted" anti-cancer drug delivery system improved the therapeutic effect by 56.52% compared with A01 direct administration, and it has almost no obvious side effects. The authors accomplished a novel dual antitumor drug delivery system via the pH sensitive nanoparticles which deliver drugs to solid tumors loading with specific inhibitors of TMEM16A which is specifically overexpressed in lung adenocarcinoma.

  嘉宾简介:安海龙,教授、博士生导师、现任澳门vns威尼斯赌场科学技术研究院副院长、生物物理研究所所长、河北省特殊津贴专家、河北省学科评议组成员,天津市五一劳动奖章获得者。获得河北省杰出青年科学基金资助,入选河北省高校“百名优秀人才创新支持计划”和河北省“三三三人才工程”三层次人选。主要研究领域为离子通道结构与功能关系、离子通道与重大疾病关系以及离子通道靶标药物发现。在Journal of Biological Chemistry、British Journal of Pharmacology, Journal of Membrane Biology等国内外学术刊物发表学术论文48篇,被SCI收录30余篇(总影响因子:126.41,其中SCI一区论文12篇,二区论文6篇)。主持、承担国家、省部级项目20项(其中国家自然科学基金重点项目2项,河北省杰出青年科学基金1项)。获得河北省优秀博士论文奖、河北省自然科学二等奖(第二名)、三等奖(第四名)各1项。

 

  报告题目(四):Graphene Oxide-Conjugated Polymer Hybrid Materials for Protein Sensing

  报告嘉宾:邢成芬

  报告简介:The new functional materials and efficient approaches for protein sensing is promising for understanding the molecular mechanism of signal transduction pathways and developing antagonists for therapy. In our recent study, we have designed and developed a novel and unconventional hybrid material consisting of graphene oxide (GO) and cationic conjugated polymer for detection of the conformation transition of a cellular Ca2+-binding protein of 148 calmodulin (CaM) by using fluorescence resonance energy transfer (FRET) technique. This effort provides first example of how FRET technique can be used with emerging types of graphene oxide and optical functional materials in order to detect CaM and its conformation change not readily obtained otherwise. We also have developed a water-soluble poly(phenylene vinylene) derivative (PPV-NMe3+)-based system to detect and inhibit the HEWL aggregation triggered by UV illumination. PPV-NMe3+ will be of theoretical and practical significance for the better understanding of protein aggregation and provides an efficient strategy to prevent and treat diseases caused by proteins aggregation. This system will produce a profound influence on the future protein drug development, meaningful for the realization of the rapid commercialization of protein drug.

  嘉宾简介:邢成芬,教授、博士生导师、省政府特殊津贴专家、省百人计划入选者,学校“元光学者”特聘B岗,河北省特聘专家,河北省青年拔尖人才、河北省杰出青年科学基金获得者、天津市创新人才推进计划青年科技优秀人才、天津市五一劳动奖章获得者,在 J. Am. Chem. Soc.、Adv. Funct. Mater. 等国际顶级杂志上发表SCI论文近40篇,SCI他引次数600余次;获得国家授权专利6项。主持国家自然科学基金面上项目 2 项、省市级项目 6 项。2016年团队获批河北省“重点培育创新团队”。

 

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