On Wednesday 3 June 2020, J. Sun will defend her PhD dissertation, entitled: ‘Amino Acid Shortages as Cancer Vulnerabilities’.
Early in 1961, L-asparaginase (ASNase), originated from guinea pig serum, was found to have anti-lymphoma effect and later on it was approved by the Food and Drug Administration (FDA), and incorporated for acute lymphoblastic leukemia treatment. So far, the progress of ASNase in childhood ALL is quite impressive, with an overall survival rate of ~90%. This had greatly encouraged further application of ASNase in other tumor types. However, several clinical trials indicated severe toxicity of ASNase due to increasing dosage. Asparagine synthetase (ASNS) was canonically proposed to be responsible for ASNase resistance. However, we thought the general nutrient sensing machinery (GCN2-ATF4-ASNS axis) as a common and essential response to nutrient starvation but not sufficient to induce this resistance. Hence, it was of great interests to investigate if other genes or pathways were involved in ASNase response besides the GCN2-ATF4-ASNS axis. In this thesis, we initiated a genome-wide CRISPR functional screen in PC3 cells and identified SLC1A3 as a contributor to ASNase resistance.
The PhD defences will not take place publicly in the Senate Hall or Professor Andries Queridoroom due to the coronavirus. The candidates will defend their thesis online.