Cellular Responses to DNA Damage

我们正在研究核膜蛋白的一个子集在细胞周期和DNA损伤反应中协调核结构动态变化中的作用。我们已经确定了细胞周期依赖的翻译后修饰位点，并正在使用各种功能测定来确定这些修饰在响应细胞分裂和DNA损伤信号时所起的作用。此外，我们还开发了一种crispr -cas9工程细胞报告系统，用于小分子化学文库的高通量检测中筛选细胞周期阻滞和凋亡。我们希望这个报告系统能够在早期的凋亡药物文库筛选中产生重要的新信息，从而促进后续的验证步骤。使用全基因组敲低筛选，我们正在确定在使用选定的化合物诱导有丝分裂中的细胞周期阻滞并随后导致细胞死亡的细胞治疗后改变或中断的分子途径。

We are examining the role of a subset of nuclear membrane proteins in coordinating dynamic changes in nuclear architecture during the cell cycle and in response to DNA damage. We have identified sites of cell cycle-dependent post-translational modification and are using a variety of functional assays to define the roles these modifications play in response to signals for cell division and DNA damage. In addition, we have developed a CRISPR-cas9-engineered cell reporter system to screen for cell cycle arrest and apoptosis in high-throughput assays of small molecule chemical libraries. We hope this reporter system will yield important new information in early rounds of library screening for apoptotic agents that will facilitate subsequent validation steps. Using genome-wide knockdown screens, we are identifying molecular pathways that are altered or disrupted in response to treatment of cells with selected compounds that induce cell cycle arrest in mitosis and subsequently, cell death.