It's beginning to look like a strange new RNA world exists! Observations by our lab and others have shown that noncoding RNAs (ncRNAs) play an underappreciated role in controlling gene expression in human cells. Studies from our lab have determined that in human cells both long and short ncRNAs can epigenetically regulate gene expression and transcription. These findings suggest that the once held dogma that RNA functions as an information transfer medium between DNA and protein may be incomplete. Evidence suggests that some RNAs may also be governing particular protein and DNA interactions, such as epigenetic states, that may not only guide natural selective states in the cell but also prove to be exceptionally valuable and therapeutically relevant molecules to target.
Our lab is interested in determining how ncRNAs regulate gene expression and dictate epigenetic states and to what extent this mechanism is operative in shaping the content and architecture of the human genome. Specifically we wish to apply this knowledge to transcriptionally control HIV-1, cancer and diseases such as cystic fibrosis.
Ongoing projects in the Morris lab include: mechanistic determination of small and long ncRNA mediated transcriptional gene silencing (TGS) and epigenetic gene regulation in human cells; TGS of HIV-1 and several oncogenes involved in human cell cancers; transcriptional gene activation/de-repression, whereby we utilize ncRNAs, antisense oligonucleotides or zinc-finger activator conjugates targeted to endogenous regulatory long ncRNAs; and nucleic acid based genetic therapy targeted approaches to delivering regulatory ncRNAs or gene specific zinc-finger activator/repressors to cells to treat different diseases. Current methods involve developing receptor targeted aptamers and mobilization competent lentiviral vectors to parasitize HIV-1.