CIRCADIAN REGULATION OF HIF2alpha IN RENAL CELL CARCINOMA

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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.