低氧微环境是实体瘤的标志特征,也是促进肿瘤生长与转移的重要因素。HIF(hypoxia-inducible factor)信号通路在肿瘤细胞的低氧应答过程中发挥主导作用,但是HIF信号通路受调控的分子机制及其促进肿瘤发生发展的机理还远未研究清楚。更重要的,现有HIF小分子抑制剂存在抗肿瘤效果差、副作用大等弊端。我们将综合利用质谱、蛋白质组学、转录组学、小鼠模型等技术手段研究HIF信号通路,主要研究方向包括:(1)HIF信号通路, 特别是其核心蛋白质HIF-α、VHL和PHD,感知低氧的分子机制。(2)肿瘤低氧/HIF信号通路对细胞骨架等细胞结构的影响。(3)筛选HIF信号通路重要调控因子的小分子抑制剂,或者用PROTAC技术靶向降解这些调控因子。研究课题得到了国家自然科学基金、广东省自然科学基金、广州市科技局项目、中央高校基本科研业务费项目等的资助。
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