蛋白质构象疾病的可视化分析

蛋白质的错误折叠与聚集会引发多种人类退行性疾病，如：阿尔兹海默症、帕金森症、渐冻人症和淀粉样变心肌病等，统称为蛋白质构象疾病。课题组围绕一个核心科学问题，即聚集态蛋白质的形成、发展和清理机制，探索聚集态蛋白质的化学探测和识别原理，发展荧光靶向探针实现活细胞内聚集态蛋白质的动态成像和理化性质测量，建立聚集态蛋白质组组分分析工具。

具体研究方向：

​1. 聚集态蛋白质的成像分析：发展荧光靶向探针，示踪致病蛋白质的错误折叠与聚集过程。

2. 聚集态蛋白质的组分分析：发展邻近标记探针，捕获致病蛋白质及其周边互作组分，解析致病机制。

3. 淀粉样变疾病的早期诊断、精准分型与临床试剂盒的开发。

招收有机化学、分析化学和化学生物学背景的硕士研究生和博士研究生。

070303-有机化学

生命分析，化学生物学

2010-08--2015-09   美国斯克里普斯研究所   化学博士
2006-08--2010-06   新加坡国立大学   应用化学一等荣誉学士

   

2019-01~现在, 中国科学院大连化学物理研究所, 研究员
2015-10~2018-12,美国宾州州立大学, 博士后

   

（1） Tailoring the positive and negative solvatochromism for chalcone analogues to detect heterozygous protein co-aggregation, CHEMICAL COMMUNICATIONS, 2023, 通讯作者
（2） Chemical probes for investigating protein liquid-liquid phase separation and aggregation, CURRENT OPINION IN CHEMICAL BIOLOGY, 2023, 第 3 作者
（3） Identification of a novel transthyretin mutation D39Y in a cardiac amyloidosis patient and its biochemical characterizations, FRONTIERS IN CARDIOVASCULAR MEDICINE, 2023, 通讯作者
（4） Solvatochromic Cellular Stress Sensors Reveal the Compactness Heterogeneity and Dynamics of Aggregated Proteome, ACS SENSORS, 2022, 通讯作者
（5） Detecting the insoluble protein aggregates in live cells using an AIE derivative of fluorescent protein chromophore, SENSORS AND ACTUATORS B-CHEMICAL, 2022, 第 6 作者
（6） Chemical Biology Toolbox to Visualize Protein Aggregation in Live Cells, CHEMBIOCHEM, 2022, 通讯作者
（7） Derivatizing Nile Red fluorophores to quantify the heterogeneous polarity upon protein aggregation in the cell, CHEMICAL COMMUNICATIONS, 2022, 通讯作者
（8） Deep Learning-Based Morphological Classification of Endoplasmic Reticulum Under Stress, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2022, 第 8 作者
（9） A Novel Virus Detection Strategy Enabled by TR512-Peptide-Based Bioorthogonal Capture and Enrichment of Preamplified Nucleic Acid, ANALYTICAL CHEMISTRY, 2022, 通讯作者
（10） Biochemical and biophysical properties of an unreported T96R mutation causing transthyretin cardiac amyloidosis, AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, 2022, 通讯作者
（11） Covalent Proteome Solvatochromic Proteome Stress Sensor Based on Schiff Base Reaction., Anal. Chem, 2022, 通讯作者
（12） Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility, AGGREGATE, 2022, 第 13 作者
（13） A Solvatochromic Fluorescent Probe Reveals Polarity Heterogeneity upon Protein Aggregation in Cells, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 通讯作者
（14） Covalent Probes for Aggregated Protein Imaging via Michael Addition, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 通讯作者
（15） Quantitative interrogation of protein co-aggregation using multi-color fluorogenic protein aggregation sensors, CHEMICAL SCIENCE, 2021, 通讯作者
（16） Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores, ANALYTICAL CHEMISTRY, 2021, 通讯作者
（17） AggFluor: Fluorogenic Toolbox Enables Direct Visualization of the Multi-Step Protein Aggregation Process in Live Cells, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2021, 第 8 作者
（18） A quinoline-benzothiazole hybrid as the first near-infrared fluorescent probe for transthyretin, NEW JOURNAL OF CHEMISTRY, 2021, 第 5 作者
（19） Derivatizing merocyanine dyes to balance their polarity and viscosity sensitivities for protein aggregation detection, CHEMICAL COMMUNICATIONS, 2021, 通讯作者
（20） A quinoline derived D-A-D type fluorescent probe for sensing tetrameric transthyretin, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2021, 第 5 作者
（21） Regulation of Fluorescence Solvatochromism To Resolve Cellular Polarity upon Protein Aggregation, ANALYTICAL CHEMISTRY, 2021, 通讯作者
（22） Illuminating Protein Phase Separation: Reviewing Aggregation-Induced Emission, Fluorescent Molecular Rotor and Solvatochromic Fluorophore Based Probes, CHEMISTRY-A EUROPEAN JOURNAL, 2021, 通讯作者
（23） Rational Design of Crystallization-Induced-Emission Probes To Detect Amorphous Protein Aggregation in Live Cells, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 通讯作者
（24） A General Strategy to Enhance Donor-Acceptor Molecules Using Solvent-Excluding Substituents, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, 第 8 作者
（25） Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress, EMBO JOURNAL, 2020, 第 3 作者
（26） A SNAP-tag fluorogenic probe mimicking the chromophore of the red fluorescent protein Kaede, ORGANIC & BIOMOLECULAR CHEMISTRY, 2019, 第 6 作者
（27） A Fluorogenic AggTag Method Based on Halo- and SNAP-Tags to Simutaneously Detect Aggregation of Two Proteins in Live Cells, ChemBioChem, 2019, 第 1 作者
（28） Monitoring Proteome Stress in Live Cells Using HaloTag-Based Fluorogenic Sensor. Book Chapter, Protein Misfolding Diseases, 2019, 第 1 作者
（29） Super-Resolution Optical Lithography with DNA, NANO LETTERS, 2019, 第 2 作者
（30） A Molecular Rotor-Based Halo-Tag Ligand Enables a Fluorogenic Proteome Stress Sensor to Detect Protein Misfolding in Mildly Stressed Proteome, BIOCONJUGATECHEMISTRY, 2018, 第 3 作者
（31） Modulation of Fluorescent Protein Chromophores To Detect Protein Aggregation with Turn-On Fluorescence, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2018, 第 1 作者
（32） A HaloTag-Based Multicolor Fluorogenic Sensor Visualizes and Quantifies Proteome Stress in Live Cells Using Solvatochromic and Molecular Rotor-Based Fluorophores, BIOCHEMISTRY, 2018, 第 1 作者
（33） Heat Shock Protein Reports on Proteome Stress, BIOTECHNOLOGY JOURNAL, 2018, 第 1 作者
（34） HaloTag-Based Multicolor Fluorogenic Sensor Visualizes and Quantifies Proteome Stress in Live Cells Using Solvatochromic and Molecular Rotor-Based Fluorophores., Biochemistry, 2018, 第 1 作者
（35） AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2017, 第 1 作者
（36） The Cation-pi Interaction Enables a Halo-Tag Fluorogenic Probe for Fast No-Wash Live Cell Imaging and Gel-Free Protein Quantification, BIOCHEMISTRY, 2017, 第 1 作者
（37） Synthesis of Sulfotyrosine-Containing Peptides by Incorporating Fluorosulfated Tyrosine Using an Fmoc-Based Solid-Phase Strategy, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2016, 第 4 作者
（38） Stabilizing the C H 2 domain of an Antibody by Engineering in an Enhanced Aromatic Sequon, ACS CHEMICAL BIOLOGY, 2016, 第 5 作者
（39） Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding-site Tyr Residue, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 第 7 作者
（40） A Fluorogenic Aryl Fluorosulfate for Intraorganellar Transthyretin Imaging in Living Cells and in Caenorhabditis elegans, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2015, 第 2 作者
（41） Individual and Collective Contributions of Chaperoning and Degradation to Protein Homeostasis in E. coli, CELL REPORTS, 2015, 第 4 作者
（42） FluorescenceTurn-On Folding Sensor To Monitor ProteomeStress in Live Cells, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2015, 第 1 作者
（43） Heat-Shock Response Transcriptional Program EnablesHigh-Yield and High-Quality Recombinant Protein Production in Escherichia coli, ACS CHEMICAL BIOLOGY, 2014, 第 2 作者
（44） Fluorogenic Small Molecules Requiring Reaction with a Specific Protein to Create a Fluorescent Conjugate for Biological Imaging–What we Know and What we Need to Learn, BIOPOLYMERS, 2014, 第 3 作者
（45） Small molecule probes to quantify the functional fraction of a specific protein in a cell with minimal folding equilibrium shifts, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 第 1 作者
（46） De Novo -Designed Enzymes as Small-Molecule-RegulatedFluorescence Imaging Tags and Fluorescent Reporters, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2014, 第 1 作者
（47） Stilbene Vinyl Sulfonamides as Fluorogenic Sensors of and Traceless Covalent Kinetic Stabilizers of Transthyretin that Prevent Amyloidogenesis, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 第 2 作者

（1） Protein Misfolding Diseases, Springer, 2019-01, 第 1 作者

   

（ 1 ） 发展新型荧光方法在血浆中原位探测转甲状腺素蛋白的早期错误折叠态, 负责人, 国家任务, 2020-01--2022-12
（ 2 ） 发展新型荧光探针解析致病蛋白质的错误折叠过程及筛选药物分子, 负责人, 地方任务, 2020-01--2022-12
（ 3 ） 聚集态蛋白质的成像分析, 负责人, 国家任务, 2023-01--2025-12
（ 4 ） 建立转甲状腺素蛋白血浆动力学稳定性的中国地区测量平台, 负责人, 其他任务, 2022-03--2023-03
（ 5 ） 前白蛋白血浆稳定性高通量荧光检测方法的研究, 负责人, 企业委托, 2021-01--2022-01

现指导学生

白玉龙  博士研究生  070303-有机化学  

张怀月  硕士研究生  070303-有机化学  

冯焕  博士研究生  070303-有机化学  

王梦蝶  博士研究生  070303-有机化学  

肖永全  硕士研究生  070303-有机化学  

高蕊  硕士研究生  070303-有机化学  

孙瑞  博士研究生  070303-有机化学  

夏秋璇  博士研究生  070303-有机化学