Specialized translation mechanisms in development and disease

Overview

A fundamental question in cell biology is how 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.

We are focused on understanding how gene regulation occurs through novel mechanisms of mRNA translation. Specifically, we study how non-canonical translation pathways shape cell growth and differentiation. Accumulating evidence supports the essentiality of mRNA translation control in these cell fate decisions, including abundant genetic links between dysregulation of translation initiation factors with malignancy, inheritable diseases, and behavioral disorders.

Lab Projects

Our research is at the nexus of combining discovery and mechanism-based studies, and thus we use genome-wide and computational approaches together with molecular genetics, cell biology, biochemistry, and structural biology techniques. We aim to contribute to understanding the significance of translational control during cell growth decisions by addressing the following questions:

+ How do we discover non-canonical translation pathways that shape the decisions of the cell to undergo cell growth, proliferation, or differentiation into different cell types?

+ How are the functions of RNA-binding proteins and translation factors regulated by intra- and extracellular environmental signals?

+ Why does dysregulation of transcript-specific translation lead to carcinogenesis and developmental diseases; and can we therapeutically target RNA-protein interactions for disease intervention?



All content ©️Amy Lee 2017