表皮生长因子受体（EGFR）是受体酪氨酸激酶家族成员之一，在细胞生长、增殖、分化和迁移等过程中具有重要的调控作用。EGFR过表达或突变与多种癌症密切相关, 已成为一个主要的癌症治疗靶点和预后指标。越来越多的研究揭示EGFR可通过多种内吞途径进入细胞，并介导不同的生理和病理功能，然而其不同内吞途径命运选择的分子机制仍不清楚，是内吞介导细胞信号转导领域的一个关键科学问题和研究难点。针对这一重要科学问题和研究前沿，本项目中我们将整合活细胞多色单分子荧光成像、多色单分子追踪定量分析、超高分辨率三维成像和基因编辑等多种先进技术，研究EGFR在不同外界或内在因素影响下如何动态选择不同的内吞途径，具有很强的创新性和重要科学意义。研究结果将揭示EGFR内吞途径选择及调控的分子机制，建立的新技术方法和体系也将为研究其他重要信号通路的内吞调控机制提供新的技术方法和研究思路。

Epidermal growth factor receptor (EGFR) is a member of receptor tyrosine kinase family, which plays important roles in regulating a variety of biological processes such as cell growth, proliferation, differentiation and migration. EGFR overexpression and mutation is involved in the development of different types of cancers. Thus, EGFR has become a critical therapeutic target and prognosis marker of cancer. Many recent studies have revealed that EGFR could enter cells via different endocytosis pathways, which mediate distinct physiological and pathological consequences. However, the molecular mechanism on how EGFR chooses different endocytosis pathways is largely unknown. This has become one of the most important unanswered questions as well as challenge in the membrane trafficking and cell signal transduction fields. In this project, we will employ a series of cutting-edge techniques such as live-cell multi-color single-molecule imaging, quantitative single-molecule imaging analysis, high-resolution 3D imaging and genome editing to systematically investigate the mechanism of endocytic pathway selection of EGFR under different external or internal stimulation and perturbation. The methodology innovation will change the way we study endocytosis and cell signaling. Thus, by using these cutting-edge multidisciplinary approaches, this project will uncover the molecular mechanism of EGFR endocytic pathway selection and will provide new tools and strategies for the membrane trafficking and cell signaling research fields.