WEHI Wednesday Seminar hosted by Professor Andreas Strasser

Annabella Thomas
PhD Student – Strasser Laboratory, Blood Cells & Blood Cancer division – Cancer Research & Treatments Theme, WEHI (this is a PhD Completion seminar)
 

Investigating p53 activated cellular responses to understand tumour suppression

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

The p53 protein regulates hundreds of genes involved in several cellular responses that suppress tumorigenesis. Accordingly, the p53 gene is mutated in ~50% of human cancers and is linked to poor patient outcomes. Despite extensive research, it is still not fully understood what determines which cellular process – cell death or cell cycle arrest – is preferentially induced in a cell following p53 activation, or whether the same processes are induced if p53 is activated with drugs (DNA damaging or non-genotoxic drugs) or by oncogenes.

To address these questions, a ‘double reporter’ mouse was made to simultaneously report on the p53 target gene p21, which is required for p53-mediated induction of cell cycle arrest/cell senescence, and Puma, which is critical for p53-mediated apoptosis. Flow cytometric analysis of primary cells ex vivo, and intravital imaging of the bone marrow of live mice was employed to track p21 and Puma reporter expression in normal cells in response to p53-activating agents and in pre-malignant and malignant cells expressing an Eµ-Myc transgene. Additionally, RNA-seq was carried out to compare the gene expression profile of primary normal cells in which p53 was activated by different stimuli. Collectively, these studies revealed new insights into p53’s tumour suppressor activity in normal and cancerous cells.

All welcome!