Summary
This research project aims to investigate the causal link between MYC-mediated BMAL1 suppression and circadian disruption in non-small cell lung cancers (NSCLCs), exploring its role in malignant transformation and resistance to glucocorticoids.
What they want
The project proposes two aims: first, to interrogate how MYC suppression of BMAL1 and circadian clock disruption drive the loss of lung alveolar cell identity and malignant cell transformation, including restoring BMAL1 in MYC-amplified lung organoids and mouse models, testing if MYC prevents BMAL1 from binding its typical DNA targets, and associating MYC, BMAL1, and malignancy in human tumor samples; second, to test how MYC and circadian disruption suppress NSCLC response to glucocorticoids, determining if MYC overrides glucocorticoid-mediated growth suppression via BMAL1 suppression and the mechanism by which MYC controls the glucocorticoid receptor and molecular clock response to glucocorticoids.
Deliverables
- Interrogation of the degree to which MYC suppression of BMAL1 and disruption of the clock drive loss of lung alveolar cell identity and malignant cell transformation.
- Testing of the degree to which MYC and circadian disruption suppress NSCLC response to glucocorticoids.
