BETRNet Roles: Project 3 Co-Investigator
- Epigenetic Regulation by Large Intervening Non-coding (linc)RNA
Our group studies the role of long non-coding RNAs (lncRNAs) in human health and disease. We specifically focus on the role of lncRNAs in regulating the epigenome, and consequently, gene expression. Many lncRNAs become dysregulated in human disease, providing novel biomarkers and therapeutic targets.
One of the most fundamental and unsolved problems in biology is: how does the same genome present in every cell of an organism encode a multitude of different cellular states? While epigenetic regulation by chromatin-modifying complexes plays a key role in this process, it is not currently known how these complexes are targeted to specific regions of the genome. We hypothesized that lincRNAs may guide chromatin-modifying complexes to specific genomic loci. Using state of the art genomic technologies we demonstrated that numerous lincRNAs associate with chromatin-modifying complexes in several human cell types (Khalil et al., 2009). Through loss-of-function experiments, we found that this subset of lincRNAs is required for proper expression of specific regions of the genome, which are known to be regulated by their associated chromatin-modifying complexes (Khalil et al., 2009).
These studies suggested that lincRNAs play a critical role in regulating gene expression, and may play critical roles in human biology. Indeed, lincRNAs have been, thus far, implicated in dosage compensation, genomic imprinting, alternative splicing of pre-mRNAs, nuclear organization and nuclear-cytoplasmic trafficking (Moran et al., 2012). Also, the dysregulation of lincRNAs have been observed in many human diseases and disorders including cancer and neurological disorders, suggesting that lincRNAs could be utilized as biomarkers or drug targets (Niland et al., 2012). My lab is currently focusing on elucidating the mechanisms by which lincRNAs exert their effects.