Our group focuses on two main projects:

1 Uncovering mechanisms of long noncoding RNA (LncRNA)-mediated gene silencing. 

It has recently been appreciated that the majority of the human genome has the capacity to be transcribed into RNA.  Some of these non-protein coding RNA products, made from what was once considered "junk DNA," can have specific functions in the cell, such as contributing to gene regulation.  We have focused on investigating the molecular mechanism behind long noncoding RNAs that regulate heterochromatin.  Recently, we have generated a new model for how a LncRNA called HOTAIR may choose its target genes via RNA-RNA matchmaking.  HOTAIR has roles in developmental patterning and overexpression in cancer leads to aberrant gene silencing that promotes aggressive cancer characteristics.  By studying how LncRNAs work at the molecular level, we have a shot at figuring out how to control them in disease to reset normal epigenetic states.
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2 Using budding yeast heterochromatin as a model to comprehensively characterize a specific chromatin domain.  

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The genetics of budding yeast chromatin-mediated gene silencing have provided an extensive foundation for understanding chromatin biology in all eukaryotes.  This model system is distinguished by the minimal set of components necessary for gene silencing.  The next step for this model is to provide new insights through biochemistry.  We have demonstrated that a functional yeast heterochromatin domain can be assembled in the test tube, and uncovered how versatile heterochromatic gene silencing is, even in its most stripped-down form in budding yeast.
Projects include:
  • The interplay of heterochromatin and DNA replication
  • Detailed biochemical analysis of interactions between RNA Polymerase II and silencing factors.
  • Understanding the mechanism of directional spreading of the silencing structure along a chromatin fiber.
  • How heterochromatin is re-established in an epigenetic pattern.
  • Comprehensive characterization of the yeast heterochromatin interactome using quantitative proteomics.