Zhan Yao

From the outset my career focus and program of work have been directed toward understanding the molecular basis of tumor development with the goal of improving cancer therapies. At the University of Science and Technology of China, my PhD thesis research investigated protein post-translational modifications and their functions in the regulation of cell death. Subsequently, as a postdoc at Cold Spring Harbor Laboratory, I studied the oncogenic signaling pathways EGFR, PDGFR and TGFβ, which regulate the development and progression of lung adenocarcinomas. In 2012, I joined Neal Rosen Lab, and since then, my work has mainly focused on the oncogenic activation of ERK signaling in human tumors, and I have shown that different mutant alleles of BRAF have unique mechanisms of action and are sensitive to different targeted therapies. We are now extending a similar analysis to tumor-associated MEK1, ARAF and RAF1 mutant alleles. In addition, my research has also contributed significantly to the biochemical analysis of oncogenic mTOR mutants. My work suggests that mTOR mutations in different domains are associated with reduced sensitivities to current mTOR inhibitors by different mechanisms. In collaboration with the Shokat lab at UCSF, we developed a new type of mTOR inhibitor with a much higher potency than other currently available inhibitors, and which reduces the drug resistance mediated by mutations of mTOR. Overall, my research work has contributed significantly toward the deconvolution of complicated molecular mechanisms underlying complex and diverse tumor genotypes and the development of individualized treatment regimens for many patients. From July 2020, I joined LOXO oncology at Lilly and act as a Director to lead the mechanistic Biology team to study the mechanisms of actions of multiple drug candidates in tumor models.