Cancer metastasis is the leading killer for cancer patients. However, the molecular mechanisms supporting metastatic cancer cells grow, migrate and colonize distant organs are poorly understood, limiting our capability in developing effective anti-cancer therapies.
Yilong Zou uncovered that the polyunsaturated ether-phospholipids synthesized by the peroxisomes as key substrates mediating lipid peroxidation and ferroptosis, and revealed the plasticity of the membrane lipidome as a critical feature enabling the evasion of ferroptotic cell death by cancer cells. This work sheds light on the durability of the efficacy of ferroptosis-inducing agents in cancer and provides a mechanism by which cancer cells resist ferroptosis induction. Moreover, Zou employed genome-wide CRISPR screens to identify cytochrome P450 Oxidoreductase (POR) as a key regulator of ferroptosis, enabling specific targeting of the ferroptosis pathway.
Zou also developed the Photochemical Activation of Lipid Peroxidation (PALP) technology that enables rapid stratification of cancer patients for their sensitivity to ferroptosis induction, accelerating the translation of ferroptosis-targeted anti-cancer therapies into the clinics.
Zou was the first to use Translating Ribosome Affinity Purification and Sequencing (TRAP-Seq) to characterize the transcriptional profile of metastatic cancer cells in situ. Later, he jointly developed an advanced version of the GSEA software, namely Gene List-Network Enrichment Analysis (GELiNEA), and a liposome-mediated phospholipid delivery method, both widely used in the field.
Zou’s next exciting goal is to use current and novel spatial multi-omics technologies including mass spectrometry imaging to dissect the molecular mechanisms underlying important human diseases, including metastatic cancers, and facilitate the development of novel anti-cancer therapeutics.