申请人主要从事抑癌蛋白p53的失活机理研究，致力于获得具广泛用药范围的靶向药物：p53功能恢复药物。申请人首次揭示了黑素瘤中p53凋亡功能的缺失机理；命名了p53抑制蛋白的“RaDAR”核定位信号；并获得了具全球知识产权的p53功能恢复药物JNJ-7706621，这对全球一半的癌症患者具潜在治疗价值。近年来申请人提出并命名了“SMaRT”转录调控模式，这将修改欧美教材《Molecular Cell Biology》，并为研究癌症的转录失调提供新方向。一系列研究成果连续发表在Cancer Cell、Cell、Nature Reviews Molecular Cell Biology，被认为“提高了领域的研究层次（puts the bottom line up top in the field）”。本项目拟筛选能恢复突变型p53结构和功能的化合物，这将填补 “抑癌蛋白”靶向药物的空白。

The applicant devotes himself to understanding how tumor suppressor p53 is dysfunctional in cancers, aiming to develop the p53-reactivating drug, a targeted drug with the widest application range in cancer patients. In the past decade, the applicant uncovered the mechanism how pro-apoptotic function of p53 was inactivated in melanomas; named the “RaDAR” nuclear import pathway employed by p53 inhibitor; developed a patent protected p53-reactivating compound JNJ-7706621 which could be potentially applied on half of cancer patients. In recent years, the applicant proposed a pathway called “SMaRT signalling”, this provides a new research direction for transcriptional dysregulation. The series of studies were published on journals including Cancer cell, Cell, and Nature Reviews Molecular Cell Biology, and were commented as ‘puts the bottom line up top in the field’. The current study aims to screen compounds restoring conformation and function to mutant p53, which may be potentially developed into the first drug targeting tumor suppressor.