報(bào)告時(shí)間：2019年6月10日（周一）9:30
報(bào)告地點(diǎn)：北辰校區(qū)生物物理研究所108會(huì)議室
報(bào)告題目（一）：Finding New Anti-Arrhythmic Drugs
報(bào)告嘉賓：Jianmin Cui
報(bào)告簡(jiǎn)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(jiǎn)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(bào)告題目（二）：Targeted genome modification in plants using CRISPR/Cas9
報(bào)告嘉賓：李君
嘉賓簡(jiǎn)介：李君，首都師范大學(xué)博士后，主要從事（1）植物基因組編輯技術(shù)及新方法的開(kāi)發(fā)利用。首次將CRISPR/Cas9技術(shù)應(yīng)用于植物中進(jìn)行植物基因組編輯；在水稻中建立了一種高效的基因定點(diǎn)替換及插入的基因組編輯體系；利用CRISPR/Cas9技術(shù)在玉米中創(chuàng)制了TMS5突變體，表現(xiàn)溫敏雄性不育的表型；利用CRISPR/Cas9技術(shù)對(duì)擬南芥基因組進(jìn)行定點(diǎn)編輯；（2）基因表達(dá)調(diào)控在植物發(fā)育和適應(yīng)環(huán)境中的作用和機(jī)制。以模式植物擬南芥為材料，主要采用遺傳學(xué)、細(xì)胞生物學(xué)、分子生物學(xué)以及生物化學(xué)等技術(shù)手段研究基因表達(dá)調(diào)控植物發(fā)育和適應(yīng)環(huán)境的分子機(jī)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(guó)際影響力的學(xué)術(shù)期刊上發(fā)表多篇論文。
報(bào)告題目（三）：Drug screening targeting at TMEM16A/CaCCs and dual-target antitumor strategy based on pH sensitive nanoparticles
報(bào)告嘉賓：安海龍
報(bào)告簡(jiǎn)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(jiǎn)介：安海龍，教授、博士生導(dǎo)師、現(xiàn)任河北工業(yè)大學(xué)科學(xué)技術(shù)研究院副院長(zhǎng)、生物物理研究所所長(zhǎng)、河北省特殊津貼專家、河北省學(xué)科評(píng)議組成員，天津市五一勞動(dòng)獎(jiǎng)?wù)芦@得者。獲得河北省杰出青年科學(xué)基金資助，入選河北省高?！鞍倜麅?yōu)秀人才創(chuàng)新支持計(jì)劃”和河北省“三三三人才工程”三層次人選。主要研究領(lǐng)域?yàn)殡x子通道結(jié)構(gòu)與功能關(guān)系、離子通道與重大疾病關(guān)系以及離子通道靶標(biāo)藥物發(fā)現(xiàn)。在Journal of Biological Chemistry、British Journal of Pharmacology, Journal of Membrane Biology等國(guó)內(nèi)外學(xué)術(shù)刊物發(fā)表學(xué)術(shù)論文48篇，被SCI收錄30余篇（總影響因子：126.41，其中SCI一區(qū)論文12篇，二區(qū)論文6篇）。主持、承擔(dān)國(guó)家、省部級(jí)項(xiàng)目20項(xiàng)（其中國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目2項(xiàng)，河北省杰出青年科學(xué)基金1項(xiàng)）。獲得河北省優(yōu)秀博士論文獎(jiǎng)、河北省自然科學(xué)二等獎(jiǎng)（第二名）、三等獎(jiǎng)（第四名）各1項(xiàng)。
報(bào)告題目（四）：Graphene Oxide-Conjugated Polymer Hybrid Materials for Protein Sensing
報(bào)告嘉賓：邢成芬
報(bào)告簡(jiǎn)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(jiǎn)介：邢成芬，教授、博士生導(dǎo)師、省政府特殊津貼專家、省百人計(jì)劃入選者，學(xué)?！霸鈱W(xué)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(xué)基金獲得者、天津市創(chuàng)新人才推進(jìn)計(jì)劃青年科技優(yōu)秀人才、天津市五一勞動(dòng)獎(jiǎng)?wù)芦@得者，在 J. Am. Chem. Soc.、Adv. Funct. Mater. 等國(guó)際頂級(jí)雜志上發(fā)表SCI論文近40篇，SCI他引次數(shù)600余次；獲得國(guó)家授權(quán)專利6項(xiàng)。主持國(guó)家自然科學(xué)基金面上項(xiàng)目 2 項(xiàng)、省市級(jí)項(xiàng)目 6 項(xiàng)。2016年團(tuán)隊(duì)獲批河北省“重點(diǎn)培育創(chuàng)新團(tuán)隊(duì)”。
