CIRCADIAN REGULATION OF HIF2alpha IN RENAL CELL CARCINOMA

项目概要（描述） 透明细胞肾细胞癌（ccRCC）通常由缺氧诱导的细胞因子活性增加驱动。 转录因子HIF 2a。昼夜节律协调行为和生理， 环境循环。昼夜节律的慢性紊乱，如轮班工作或 跨时区旅行会增加人们患几种癌症的风险。我们已经确定， 生物钟成分BMAL1、BMAL1和BMAL2调节HIF 2a的活性，表明 生物钟的药理学靶向为抑制HIF 2a提供了新的治疗机会 在ccRCC。 提供额外的初步数据，以支持该项目下一阶段的可行性。 为了回应评论者的担忧，我们需要额外的时间来建立肾细胞癌异种移植模型， 拉米亚实验室中的雄性和雌性免疫受损宿主小鼠。

PROJECT SUMMARY (DESCRIPTION) Clear cell renal cell carcinoma (ccRCC) is frequently driven by increased activity of the hypoxia-inducible transcription factor HIF2a. Circadian rhythms coordinate behavior and physiology with predictable daily environmental cycles. Chronic disruption of circadian rhythms, such as that experienced during shift work or travel across time zones, increases the risk of several types of cancer in people. We have established that the circadian clock components BMAL1, CRY1, and CRY2 regulate the activity of HIF2a, indicating that pharmacological targeting of the circadian clock presents a new therapeutic opportunity for suppressing HIF2a in ccRCC. To provide additional preliminary data to support the feasibility of the proposed next phase of this project in response to reviewers’ concerns, we need additional time to establish renal cell carcinoma xenograft models in male and female immunocompromised host mice in the Lamia Lab.