My lab studies oncogenic factors and pathways that drive disease progression and therapeutic resistance in colorectal cancer (CRC). We particularly focus on understanding the mechanistic basis of redundancy and crosstalk among oncoprotein-activated signaling pathways and how the functional crosstalk among these pathways promotes cancer progression and alters the therapeutic response to 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 in CRC progression.

We employ a combination of molecular, cellular, biochemical, genetic, pharmacologic, imaging, bioinformatic, animal and clinical association approaches to decipher the transcriptional and post-transcriptional mechanisms controlling gene expression and pathways important for the malignant transformation and metastatic progression of CRC, with the ultimate goal of developing novel biomarkers and therapies for improving the diagnosis and treatment of this disease. In addition, we are interested in developing natural product-based small molecular inhibitors for targeting translational control of CRC and potentially other major cancers.