“The Pelletier Lab focuses on mechanisms of translational control in normal and pathological settings. Translation is a fundamental process integral to cellular protesostasis with most regulation imposed at the level of initiation. Deciphering regulatory networks that govern this process is vital to understanding both normal and abnormal cell survival, differentiation, and proliferation. To this end, our laboratory uses the tools of chemical biology, RNAi screening technology, and tractable mouse models to probe and target various aspects of translation in specific settings. Our laboratory is also developing tools of genome engineering to dissect regulatory events in vivo.”
Our laboratory studies translational control - defining features that regulate this process under normal conditions and that become perturbed in disease. We are also interested in mRNA structure-function relationships, especially as determinants of translational efficiency. We have adapted genome engineering tools for genetic screens and aim to apply these to the study of translation in vivo.
Previous work in our laboratory has probed the ribosome recruitment phase of translation initiation in determining quantitative and qualitative mRNA translational output. We have investigated the role that initiation factors play in recruiting ribosomes to mRNA templates, focusing on the role of RNA helicases eIF4AI and eIF4AII. We have shown that manipulation of translation initiation can be a potent barrier to tumor initiation/maintenance and contributes to the anti-tumor action of chemotherapeutic drugs by selectively affecting the production of pro-survival and cell cycle proteins.
To facilitate our research, we combine chemical biology, molecular genetic, and genomic tools that enable us to explore the contribution of deregulated translation to cancer biology in a comprehensive way. We have 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 genome engineering technology to suppress gene function in a stable manner. Current efforts strive to integrate powerful mouse cancer models, chemical biology, and genome engineering to explore the role of translation in tumor maintenance and cell death mechanisms and characterize their impact on treatment response.