近几年申请人主要围绕肿瘤代谢展开研究，发现打破代谢平衡能特异杀死肿瘤细胞，为进一步揭示其分子机制，申请人开发了可实时监测细胞死亡方式的研究平台，用于筛选调控细胞死亡的代谢途径，发现葡萄糖代谢在维持细胞内微环境过程中起了重要作用并能调控细胞的死亡及死亡方式。这些成果主要发表在Cancer cell（第一作者）和Nature Commun.（通讯作者）上。我们构建了各种筛选库，拟以乳腺肿瘤细胞为模型筛选并分析这些代谢反应及相关途径揭示代谢驱动的微环境和细胞死亡之间的关系及相互调控机制，并进一步从葡萄糖、脂肪酸及氨基酸的异常代谢入手，寻找肿瘤细胞得以生长转化的化学本质。近几年申请人发表第一作/通讯作者论文6篇，累积影响因子超60，工作获国内国际同行认可，先后被Science及Cancer Research报道，获亚洲癌症基金优秀学者奖，主持国家自然科学基金两项，入选天津市第一层次培养人才。

The applicant has been engaged on metabolism-associated research for many years. In recent years, it has become clear that many of the signaling pathways that are affected by genetic mutations and the tumor microenvironment converge to affect core metabolism, indicating the metabolism is the direct regulator of cellular activities. However, how metabolism determines cell fate, such as growth, transformation and death, largely remains elusive. In recent five years, the applicant focuses on cancer metabolism, and reveals that the irreversible perturbation of metabolic homeostasis could specifically kill cancer cells. In order to figure out the underlying mechanism, the applicant developed a genetically-encoded switch-on fluorescence-based biosensor that fluoresces depending on protein cleavage by activated caspases. Using this biosensor, we can real-time measure cell apoptosis and further set up a screening system to identify metabolic pathways that affect cell death, apoptosis and necroptosis. These findings were mainly published in Cancer Cell (Fist author) and Nature Communications (Corresponding author). We build several libraries against metabolic pathways and use breast cancer MCF-7 cells as the model to confirm that cell metabolism determines how cancer cells die, apoptosis or necroptosis. In essence, metabolism is a pool of chemical reactions, which are largely influenced by the around context, cellular microenvironment. We aim to figure out the relationship and interaction between metabolic reactions, metabolic microenvironment and cell death, and furthermore dissect the chemical mechanisms underlying how cancer cells are transformed and survive by focusing on the cancer-associated abnormal metabolism of glucose, fatty acids and amino acids. Recently, the applicant has six publications as the first author or corresponding author, the total impact factors of which are more than sixty. The published findings are domestic and international accepted and highlighted in Science and Cancer Research. The applicant was awarded the scholarship of Asia Association for Cancer Research and also selected as one of the top talent candidates for Tianjin municipal training project.