Michael McManus, PhD


The McManus lab studies basic biological processes relating to noncoding RNAs. Shotgun sequencing and microarray hybridization have shown that the vast majority of the mammalian genome can produce RNA transcripts, although most occur at extremely low levels and show little evolutionary conservation. A major challenge in the field is thus separating the wheat from the chaff– a challenge that requires the use of innovative, high throughput approaches to address function. Our lab embraces genome-scale RNA interference (RNAi) screening and other high-throughput methodologies to uncover the functions of noncoding RNAs in the mammalian system.

Small and long noncoding RNAs. The McManus Lab uses high throughput systems to explore the biology of small and long noncoding RNAs (lncRNAs). These approaches allow us to quickly capture of broad image of which noncoding RNAs participate in a particular biological process- and place us in a position where we can focus on the few most relevant ones. It is already clear that microRNAs have broad roles across biology. Based on the few lncRNAs described to date, we hypothesize these RNAs will also have broad roles in basic biology. Our studies add significantly to our understanding of how cells react to their environments and will shed new insight into genomic noncoding RNA dark matter.

Models for studying noncoding RNAs. To date only a handful of noncoding have been functionally characterized. In an effort to understand the broad biological significance of noncoding RNAs, we have knocked out large numbers of them in mouse models. Hundreds of conditional knockout mice have been individually being made and are being characterized. Our lab is interested in understanding how noncoding RNAs contribute to the specification of cell fate and function, and how deregulation of these RNAs may contribute to human disease. There is a big future for the study of noncoding RNAs- particularly as genome deep sequencing technology matures and personalized medicine becomes a reality.

Dissecting genetic pathways for RNA biology. We are working hard to translate our basic research findings to our clinical and disease-centric colleagues. We believe that the regulatory noncoding RNAs that have been discovered are just the 'tip of the iceberg' in a set of important biology that we are far from understanding. Based on our studies of this biology, we have developed cutting-edge research tools and agents that usurp this pathway for the interrogation of gene function and the potential use in the intervention of human disease. RNAi is significantly impacting the speed at which we can validate and deliver drugs to the clinic, and it very likely constitutes the next frontier in human therapeutics.