How do cells sharing the same DNA produce drastically distinct phenotypes? In one organism, the same genome allows for the development of different tissues, controlled cell cycle progression, and specialized responses to environmental stimuli. This occurs through a process known as gene regulation, where modulation of RNA transcription and protein synthesis allow the level of expression of a gene or its gene product to be controlled. The importance of gene regulation is further underscored by its disruption being associated with a myriad of human diseases ranging from developmental diseases to carcinogenesis. The overarching goal of the Lee lab is to discover how cells sense and respond to environmental signals by modulating protein synthesis.
Specifically, the lab is focused on understanding how gene regulation occurs through novel mechanisms of mRNA translation. We seek to discover the molecular mechanisms controlling gene-specific translation and to understand how these pathways are regulated during organismal development, viral infection, and cellular stress. We are currently addressing questions including: (1) What are the gene-specific translation pathways that shape cell fate decisions? (2) How are the functions of RNA-binding proteins and translation factors regulated by environmental signals and intrinsic state? (3) Why does dysregulation of transcript-specific translation lead to carcinogenesis and developmental diseases; and can we therapeutically target RNA-protein interactions for disease intervention?
To obtain broad insights into regulation of protein synthesis, the Lee lab applies an integrative approach combining RNA-protein biochemistry, cell-based experiments, structural biology, and development of new sequencing-based technology. Our research provides mechanistic understanding of the translation regulation networks that coordinate the precise control required for correct development and cellular function.
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