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Tianwei Chen – Blood Cells & Blood Cancer division

04/12/2024 12:00 pm - 04/12/2024 1:00 pm
Location
Davis Auditorium

WEHI Wednesday Seminar hosted by Associate Professor Gemma Kelly

Tianwei Chen 
PhD Student – Kelly Laboratory, Blood Cells & Blood Cancer division – Cancer Research & Treatments Theme, WEHI (this is a PhD Completion seminar)

Understanding the role of mutant p53 in lung cancer using novel genetically engineered mouse models

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

 

The tumour suppressor gene p53 is mutated in ~50% of human cancers and this is associated with poor therapeutic responses. It is still not fully understood how mutant p53 protein promotes tumour development and growth, with three ways postulated: (1) loss of function (LOF) effects which abrogate normal p53-activated cellular processes; (2) dominant negative effects (DNE), whereby mixed tetramers formed by mutant and wild-type p53 proteins have reduced ability to control p53-regulated pathways; and (3) gain of function effects (GOF), whereby mutant p53 proteins bind to and modulate the functions of proteins that are not impacted by wild-type p53.

Our study aims to understand the role of mutant p53 in the initiation and sustained expansion of lung adenocarcinoma (LUAD). We are doing this by using novel LUAD mouse models with inducible mutant Kras-G12D and switchable p53 status within the endogenous loci. Tumorigenesis is triggered through the expression of mutant Kras-G12D and mutant p53-R246Q. Mutant p53 can be converted either back to wild-type p53 or into a p53 knock-out state when desired in the established tumour cells. In vitro and in vivo studies were performed to investigate the immediate and long-term effects of different p53 states on tumour growth. Furthermore, the therapeutic potential for LUAD of the KRAS-G12D inhibitor MRTX1133, alongside different p53 states was assessed. The findings of this research have important implications for the design of novel therapeutic approaches for p53 mutant lung cancers.

 

All welcome!

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