Aiying Yu is a Senior Scientist in the BioAnalytical Sciences Department at Genentech since 2022. She received her Ph.D. in Analytical Chemistry from Texas Tech University. She is experienced in comprehensive structural identification and quantification of proteins, glycans, and glycopeptides in various biological matrices. Her current work is focused on developing assays to enable characterization and quantification of protein therapeutics and biomarkers in fixed tissue samples such as formalin-fixed paraffin-embedded (FFPE) tissues using innovative LC-MS based approaches.
Formalin-fixed and paraffin-embedded (FFPE) tissues are a valuable resource for biomarker discovery and cancer clinical investigations. They are an attractive sample type as they are widely available and capable of preserving the integrity of pathology data for years. However, fixation of tissues results in chemical modifications and protein crosslink, which have hindered reliable quantitative analysis of proteins from FFPE tissues using MS-based proteomics methods. Here, an approach combining immunoaffinity with 2D-LC MRM was employed to achieve a reproducible approach to assess target engagement of KRAS G12C by a covalent inhibitor in FFPE tissues. Target engagement data obtained from the FFPE tissues of a KRAS G12C mouse xenograft study appeared to be comparable to those from corresponding fresh frozen tissues. The assay required a minimum of 5µg total protein extract to accomplish target engagement assessment, suggesting its feasibility to clinical samples analysis.