The transcriptional co-activators YAP and TAZ are key drivers of adult stem cell proliferation and are potent oncoproteins in many human cancers. I will describe our ongoing target validation efforts with YAP/TAZ in both squamous cell carcinoma and colorectal cancer, two of the most common human cancer types. Through the combination of mouse genetics and human cancer cell and organoid culture, we can demonstrate that targeting YAP/TAZ will be of therapeutic benefit in these cancer types. Of key interest is the notion that YAP/TAZ not only drives cell survival and proliferation, but also drives inflammation and immune evasion. Thus, targeting YAP/TAZ may not only impair tumour growth, but also make it possible to overcome resistance to immunotherapy. I will also describe our drug development efforts, including novel compounds that can potently inhibit YAP/TAZ activity with excellent tolerability and pharmacokinetics.
All are welcome. No registration required.
Prof Barry Thompson was a PhD student at the MRC-LMB in Cambridge, where he discovered new components of the Wnt signalling pathway. He was then an EMBO Long-term post-doctoral fellow at the EMBL in Heidelberg, where he began genetic analysis of Hippo-YAP/TAZ signalling and tumour formation. He then performed a genome-wide RNAi screen as a visiting scientist at the IMP in Vienna, before starting his own laboratory at Cancer Research UK, now part of the Francis Crick Institute in London, where he was awarded Tenure as a Senior Scientist and also received both the EMBO Young Investigator Award and Wellcome Investigator Award. He is currently Professor and EMBL Australia Group Leader at ANU, where he was awarded an ARC Future Fellowship. His research interests are in finding new treatments for therapy-resistant cancer, focusing on signalling mechanisms, stem cell biology, target validation with mouse genetics and human organoids, as well as targeting YAP/TAZ with novel compounds to enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy.
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