Qing-Bai She

Research in our lab focuses on the identification and characterization of oncogenic factors and pathways that drive disease progression and therapeutic resistance in colorectal cancer (CRC). We particularly investigate the mechanistic basis of redundancy and crosstalk among oncoprotein-activated signaling pathways and understand how this functional interplay promotes tumor progression and alters the response to CRC therapies. We employ a combination of molecular cell biology, biochemistry, chemical biology, pharmacology, multiomics, and mouse modeling approaches to elucidate the underlying mechanisms that control CRC progression and metastasis as well as therapeutic resistance, with the ultimate goal of developing novel biomarkers and therapies that can enhance the diagnosis and treatment of CRC. Through molecular analysis of mRNA translation states, our work establishes dysregulation of cap-dependent translation downstream of mTOR at the level of 4E-BP1/eIF4E, as a key to tumor formation, metastasis and resistance to upstream kinase-targeted therapies. Specifically, we identify 4E-BP1 as a critical node that integrates the oncogenic effects of the PI3K/AKT and RAS/RAF/MEK/ERK pathways during CRC progression. Furthermore, we have discovered and developed two new classes of natural product-based small molecular inhibitors with distinct mechanisms of action in targeting translational control of CRC and another major cancer. Recently, our group has uncovered two novel splice variants of neuropilin-1 (NRP1) that promote CRC metastasis by activating endosomal signals. Additionally, we have identified a previously unknown function of spermine synthase (SMS), a polyamine biosynthetic enzyme, that cooperates with MYC oncogene to facilitate CRC tumorigenesis. The key insights into the role of NRP1 variants in CRC metastasis and the function of SMS in CRC metabolic reprograming as well as their modulation of therapeutic outcomes are further characterizing in our lab.