Research programme 01
DREAM complex control of lung tumor suppression
We investigate how failure of DREAM-mediated transcriptional repression enables lung cells to escape quiescence and acquire tumor-promoting growth programmes.
Central question
How does disruption of DREAM assembly alter lung epithelial cell fate, tumor initiation and the response of lung cancers to therapy?
DREAM is a central transcriptional repressor of cell-cycle genes. In quiescent cells, p130 or p107, E2F4/5 and DP proteins assemble with the MuvB core to silence a broad programme of genes required for DNA replication and mitosis. The laboratory is testing how targeted disruption of this architecture changes the behaviour of lung epithelial cells and promotes oncogenic growth.
This programme uses genetically defined models to distinguish the consequences of losing DREAM itself from the broader effects of disabling RB-family proteins. The goal is to identify the molecular events that connect DREAM failure to lung tumor initiation, progression and therapeutic sensitivity.
Approaches
- Genetically engineered cell and mouse models
- CRISPR-based perturbation
- Cell-cycle and quiescence assays
- Transcriptomic profiling
- Protein-complex analysis
- Preclinical lung-cancer models
Selected work
- PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis (2021)
- The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb (2019)
- Structural mechanisms of DREAM complex assembly and regulation (2015)