Lab Members 

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Areas of Expertise:  RNA helicases, RNA-binding proteins, post-transcriptional gene regulation        

Gene expression in eukaryotes involves one of the most sophisticated biochemical networks in biology. This network involves four primary steps:  1.  synthesis of precursor messenger RNA (pre-mRNA) from a DNA template through transcription, 2. processing of the pre-mRNA to mature mRNA via splicing, capping and polyadenylation, 3.  nuclear export of the mRNA and 4. translation of the RNA into protein in the cytoplasm. A major driving force for gene expression steps is the dynamic and highly regulated alteration of ribonucleoprotein complexes (RNAs bound with RNA-binding proteins). One class of enzymes that function in regulation of RNA:protein interactions are the DEAD-box proteins, a large class of evolutionarily conserved enzymes that function in all aspects of RNA biogenesis.  Although numerous efforts have demonstrated that DEAD-box proteins perform a variety of ATP-dependent biochemical functions in vitro, the precise cellular functions for the vast majority of the ~25 members of this class have not been elucidated. 

Our laboratory uses the budding yeast Saccharomyces cerevisiae model system to define the mechanistic basis for gene regulation.  We are especially interested in post-transcriptional regulation and the roles of RNA-binding proteins and helicases in these processes. To this end, we recently provided the first documentation that the DEAD-box protein Dbp2 functions in nuclear gene expression steps (Cloutier et al., 2012).  Our studies suggest that Dbp2 modulates RNA structures or ribonucleoprotein complexes during transcription.  We are now focused on utilizing Dbp2 as a tool to define protein-coding genes that are influenced by structured elements within nascent RNA.  This involves a powerful, multidisciplinary approach that combines genome wide RNA sequencing with genetics and in vitro biochemical assays. Importantly, human Dbp2 (hDDX5) has been linked to multiple cancer types including prostate, colon and breast cancer as well as promoting chemotherapeutic drug resistance when overexpressed.  Thus, these studies are likely to reveal key insights into the molecular basis for hDDX5 in cancer development.

In addition to DEAD-box proteins, our laboratory is also interested in RNA-mediated gene regulation. In addition to proteinaceous transcription factors, recent studies have provided evidence that long non-protein-coding RNA (lncRNA) molecules also facilitate transcriptional control of protein-coding genes.  Although numerous studies have documented roles for individual lncRNAs, there is no unified model for transcriptional control.  Instead, the role of lncRNAs may be manifested through specific RNA structures encoded within these molecules. Our laboratory is currently investigating the mechanism of lncRNA-mediated transcriptional control.  We are currently defining the requirements for regulation and developing techniques to study the expression and cellular localization of lncRNAs.  LncRNA-mediated gene regulation is a newly emerging field with numerous potential for exciting discoveries.

Awards & Honors

Selected Publications