Qing-Bai She

Research in our lab focuses on identifying and characterizing oncogenic factors and pathways that drive colorectal cancer (CRC) progression and influence therapeutic outcomes. We employ a combination of molecular cell biology, biochemistry, chemical biology, pharmacology, multiomics, and mouse modeling approaches to elucidate mechanistic basis of redundancy and crosstalk among oncoprotein-activated signaling and metabolic pathways and to understand how their functional interplay promotes CRC progression, metastasis and therapeutic resistance. By leveraging these insights, we seek to develop effective therapeutic strategies to enhance CRC treatment outcomes. Through molecular analysss of mRNA translation states, our work has contributed to the growing body of evidence demonstrating that dysregulated mTORC1/4E-BP1-mediated translational control plays a critical role in cell proliferation, survival, CRC progression, and metastasis, as well as in modulating cancer cell sensitivity to upstream kinase-targeted therapies. Specifically, we identify 4E-BP1 as a critical node integrating the oncogenic effects of the PI3K/AKT and RAS/RAF/MEK/ERK pathways during CRC progression. Furthermore, we have identified and developed a new class of natural product-based small-molecular inhibitors with unique mechanisms of action, targeting translational control in CRC and other types of cancer. Recently, our group identified two novel splice variants of neuropilin-1 (NRP1) that aggressively promote CRC metastasis by activating endosomal signaling. Additionally, we uncovered a novel role of spermine synthase (SMS), a polyamine biosynthetic enzyme, as a key metabolic regulator that facilitates CRC tumorigenesis through cooperation with MYC oncogenic signaling. We are currently further characterizing the role of NRP1 variants in driving CRC progression, metastasis, and therapeutic resistance, as well as investigating the biological and therapeutic consequences of SMS inhibition in CRC tumorigenesis.