Our lab has expertise in assessing and targeting Translational Control Processes in normal and pathological settings. Translation is a fundamental process integral to cellular protesostasis with most regulation imposed at the level of initiation. Flexibility in the control of mRNA translation enables cancer cells to rapidly adapt to stress, maintain their transformed phenotype, activate metastatic programs, and acquire resistance to therapeutic intervention. The major conduit for such dynamic regulation is eukaryotic initiation factor (eIF) 4F complex (composed of eIF4E, eIF4A, and eIF4G). Increased eIF4F activity stimulates ribosome recruitment to selective mRNAs leading to increased production of factors that establish and fuel the Hallmarks of Cancer - among which prominently features the MYC proto-oncogene. Hence, eIF4F is a central regulator of gene expression, an emerging target for cancer therapy, and its inhibition is one way of suppressing the “undruggable” MYC proto-oncogene. Targeting dysregulated translational control in tumor cells is a promising approach to block the transformed phenotype and my lab holds the most potent compounds for achieving this objective (see “Research").
To facilitate our research, we combine chemical biology, molecular genetic, and genomic editing tools to explore the contribution of deregulated translation to cancer biology in a comprehensive way. We have also recently developed mouse cancer models that mimic small molecule-mediated targeted inhibition at the organismal level and have used these to validate the concept of targeting translation initiation in vivo. Furthermore, we have developed powerful methods for applying CRISPR/Cas9 genome engineering approaches to the study of translational regulation. Current efforts strive to integrate powerful mouse cancer models, chemical biology, and genome engineering to explore the role of translation in tumor initiation, maintenance, and drug response.