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學術信息

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生物與醫學前沿論壇(二)

  報告時間:2019年6月10日(周一)9:30

  報告地點:北辰校區生物物理研究所108會議室

 

  報告題目(一):Finding New Anti-Arrhythmic Drugs

  報告嘉賓:Jianmin Cui 

 

  報告簡介: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.

  嘉賓簡介: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).

 

  報告題目(二):Targeted genome modification in plants using CRISPR/Cas9

  報告嘉賓:李君

  嘉賓簡介:李君,首都師范大學博士后,主要從事(1)植物基因組編輯技術及新方法的開發利用。首次將CRISPR/Cas9技術應用于植物中進行植物基因組編輯;在水稻中建立了一種高效的基因定點替換及插入的基因組編輯體系;利用CRISPR/Cas9技術在玉米中創制了TMS5突變體,表現溫敏雄性不育的表型;利用CRISPR/Cas9技術對擬南芥基因組進行定點編輯;(2)基因表達調控在植物發育和適應環境中的作用和機制。以模式植物擬南芥為材料,主要采用遺傳學、細胞生物學、分子生物學以及生物化學等技術手段研究基因表達調控植物發育和適應環境的分子機制。

  迄今為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)等具有國際影響力的學術期刊上發表多篇論文。

 

  報告題目(三):Drug screening targeting at TMEM16A/CaCCs and dual-target antitumor strategy based on pH sensitive nanoparticles

  報告嘉賓:安海龍

  報告簡介: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.

  嘉賓簡介:安海龍,教授、博士生導師、現任河北工業大學科學技術研究院副院長、生物物理研究所所長、河北省特殊津貼專家、河北省學科評議組成員,天津市五一勞動獎章獲得者。獲得河北省杰出青年科學基金資助,入選河北省高?!鞍倜麅炐闳瞬艅撔轮С钟媱潯焙秃颖笔 叭瞬殴こ獭比龑哟稳诉x。主要研究領域為離子通道結構與功能關系、離子通道與重大疾病關系以及離子通道靶標藥物發現。在Journal of Biological Chemistry、British Journal of Pharmacology, Journal of Membrane Biology等國內外學術刊物發表學術論文48篇,被SCI收錄30余篇(總影響因子:126.41,其中SCI一區論文12篇,二區論文6篇)。主持、承擔國家、省部級項目20項(其中國家自然科學基金重點項目2項,河北省杰出青年科學基金1項)。獲得河北省優秀博士論文獎、河北省自然科學二等獎(第二名)、三等獎(第四名)各1項。

 

  報告題目(四):Graphene Oxide-Conjugated Polymer Hybrid Materials for Protein Sensing

  報告嘉賓:邢成芬

  報告簡介: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.

  嘉賓簡介:邢成芬,教授、博士生導師、省政府特殊津貼專家、省百人計劃入選者,學?!霸鈱W者”特聘B崗,河北省特聘專家,河北省青年拔尖人才、河北省杰出青年科學基金獲得者、天津市創新人才推進計劃青年科技優秀人才、天津市五一勞動獎章獲得者,在 J. Am. Chem. Soc.、Adv. Funct. Mater. 等國際頂級雜志上發表SCI論文近40篇,SCI他引次數600余次;獲得國家授權專利6項。主持國家自然科學基金面上項目 2 項、省市級項目 6 項。2016年團隊獲批河北省“重點培育創新團隊”。

 

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