RESEARCH
The ability to change protein expression on a gene-specific level is fundamental for widespread dynamic processes in cell and organismal biology. We study how this occurs through transcript-specific mRNA translation – pathways that allow the cell to alter the translation of distinct gene subsets without globally changing protein synthesis.
To obtain broad insights into regulation of protein synthesis, we apply an integrative approach combining RNA-protein biochemistry, molecular/cell approaches, structural biology, and development of new sequencing-based technologies. Our research provides mechanistic understanding of how translation precisely controls the gene expression required for correct development and cellular function.
Some of our questions include:
What are the biochemical and molecular mechanisms that drive transcript-specific translation?
Our recent findings have revealed that core translation factors and ribosomal proteins moonlight in functions outside of global protein synthesis to control gene-specific translation. We are examining the alternative roles of these factors by using RNA-protein biochemistry combined with innovative sequencing methodologies. We also seek to understand how RNA elements (structural and sequence) are targeted by these factors to drive specific mRNAs into distinct specialized translation pathways.
How is transcript-specific translation altered by cell stimuli?
Gene expression changes are a major response to cell stimuli. While global translation responses to cellular environment have been widely studied, the contribution of transcript-specific translation is not well-defined. We seek to understand how translation factors act as a signal transduction platform to integrate environmental signals into defined cellular responses and animal behavior. We are defining the stimuli, signaling events, and resulting alterations in gene programs that are incorporated through translation initiation factors.
Why does inappropriate translation lead to human disease?
Accumulating evidence reveals dysregulation of translation initiation factors is associated with malignancy, inheritable diseases, and behavioral disorders. We seek to understand the molecular mechanisms that drive carcinogenesis and developmental diseases; and to determine if we can therapeutically target RNA-protein interactions for disease intervention. We additionally are studying how viruses co-opt translation machinery to allow for preferential viral mRNA translation.