Novel Targets in Endocrine Responsiveness

内分泌反应的新靶点。虽然项目1重点分析了 围绕细胞应激和细胞命运决定的特定信号。项目2将采用功能基因组学 探讨和研究内分泌敏感和耐药细胞的细胞周期进程。韦纳博士和戈莱米斯博士 我将在项目2中领导团队，并应用我们之前已经使用的强大的合成致命屏幕方法 用于研究EGFR介导的信号转导。使用靶向已知内质网驱动基因的聚焦siRNA文库 与内分泌反应有关，我们将确定哪些基因，当它们的表达被抑制时， 影响E_2、、ICI调节细胞周期进程的能力。太重要了。SiRNA文库将是 应用于项目1中使用的相同细胞模型。该团队将验证主要影响 细胞增殖(即细胞周期)，而与特定细胞应激途径相关的候选基因 细胞存活(例如，细胞凋亡、自噬、坏死)将在项目1中进行研究。

Novel Targets in Endocrine Responsiveness. While Project 1 takes a focused analysis of specific signaling around cellular stress and cell fate decisions. Project 2 will take a functional genomics approach and study cell cycle progression in endocrine sensifive and resistant cells. Drs. Weiner and Golemis will lead the team in Project 2 and apply a powerful synthetic lethal screen approach that we have previously used to study EGFR-mediated signaling. Using a focused siRNA library targeting known ER-driven genes implicated in endocrine responsiveness, we will determine which genes, when their expression is inhibited, affect the ability of E2, TAM, and ICI to regulate cell cycle progression. Importanfiy. the siRNA library will be applied to the same cell models used in Proiect 1. The team will validate candidate genes that primarily affect cell proliferation {i.e., cell cycle), whereas candidate genes associated with specific cellular stress pathways and cell survival {e.g., apoptosis, autophagy, necrosis) will be studied in Project 1.