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研究方向 (Research Area)

蛋白质构型疾病的化学生物学研究


蛋白质分子在翻译成多肽链之后,需要准确地折叠成特定的三维结构才能行使其生理功能。蛋白质的错误折叠与聚集会引起多种蛋白质构型疾病,如:阿尔兹海默症、帕金森症、渐冻人症和淀粉样化心肌病等。然而,制约蛋白质构型疾病研究的一个重要障碍是:领域内缺乏描绘活细胞内致病蛋白质错误折叠与聚集全貌的实验方法。

课题组以淀粉样化心肌病和渐冻人症为模型疾病,开展以此类疾病为导向的化学生物学研究。核心研究方向包括:

1. 新型荧光分子全谱观测蛋白质相分离过程中的构型变化。

2. 新型早期临床诊断方法和高通量药物筛选平台。

3. 发展化学探针解析活细胞内药物靶点结合效力。


Chemical Biology of Protein Conformational Diseases

Proteins need to fold into 3-dimentional structures to achieve their physiological functions. However, aberrant protein misfolding and aggregation lead to various protein conformational diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and cardiac amyloidosis etc. Limited tools that work in live cells are available for the field to visualize the entire process of protein aggregation and dissect the pathogenic misfolded states.

Our lab is specialized in fine tuning fluorescence properties (intensity, wavelength, lifetime etc.) of chromophores towards differentiating protein misfolded states. We are particularly interested in understanding how protein misfolds and aggregates into pathogenic states during liquid-liquid and liquid-solid phase separations. We are developing fluorescent and chemical probes that can be easily used by other groups to detect protein aggregation in live cells. Currently our lab works on three major projects:

1. Development of imaging toolbox to resolve protein misfolding and aggregation states during protein phase separation.

2. Development of high throughput methods for early diagnosis and drug screening.

3. Development of chemical probes to dissect drug target engagement.


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