Yanbo Pan

RAS proteins in different locations would recruit different interaction partners and active different downstream signaling. My team will perform BioID with wide type and mutant RAS isoforms in different cancer cell lines, and then apply subcellular fractionation, farnesylation enrichment and MS-based proteomics to decipher additional functionally relevant RAS protein interactions. In addition, this research program will consider the impact of PTM and anti-RAS drug on RAS protein interaction to discover novel RAS protein interactors involved in downstream signaling or feedback and compensatory pathways which may elucidate why inhibition of downstream pathways have had limited clinical impact in cancer treatment. These data will bring novel information on poorly characterized RAS functions, e.g., its putative involvement in metabolic pathways, and on shared as well as paralog-specific protein networks that could partially explain the complexity of RAS functions. These networks of protein interactions will open numerous avenues to better understand the hidden mechanism of RAS oncogenic signaling and unveil potential therapeutic targets as well as suggest drug combinations to overcome the anti-RAS drug resistance. Moreover, the method here can be used for exploring other key proteins’ effectors to facilitate disease diagnosis and treatment.