WEHI Wednesday Seminar hosted by Associate Professor Kate Sutherland
 

Jackson McDonald
PhD Student – Sutherland Laboratory, ACRF Cancer Biology & Stem Cells division – Cancer Research & Treatments Theme, WEHI (this is a PhD Completion seminar)
 

Employing CRISPR/Cas9 screening to identify gene targets that synergise with immunotherapy in lung cancer

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

KRAS is the most frequently altered oncogene in lung adenocarcinoma (LUAD) the most common subtype of lung cancer. Recently, the development of targeted therapies has improved the treatment of a subset of patients, however the heterogeneity of KRAS-mutant LUAD remains a clinical challenge. Loss-of-function mutations found in STK11 (or Lkb1), are frequently found co-mutated with KRAS, and comprise an aggressive form of the disease, with resistance to chemotherapy. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, which aims to unleash CD8 effector T cells against tumours, are currently used as a first-line treatment strategy for KRAS-mutant LUAD patients. However, patients harbouring mutations in both KRAS and STK11 fail to respond to ICIs. Therefore, a greater understanding of the tumour-intrinsic processes that allow KRAS/STK11 mutant LUADs to evade immune detection is required for improving therapeutic outcomes.

Jackson’s PhD projects have utilised genetically engineered mouse models and CRISPR/Cas9 gene editing technologies to interrogate how KRAS/STK11 mutant cancer cells avoid immune destruction. Specifically, he has developed an in vitro co-culture CRISPR/Cas9 screening platform to identify gene targets that sensitise KRAS/STK11 mutant lung cancer cells to cytotoxic CD8 T cell killing. In this seminar, Jackson will present the establishment of the screening platform, and discuss the discovery of gene candidates that enhance the sensitivity of KRAS/STK11 mutant cancer cells to CD8 T cell killing.

All welcome!