welcome to the mcmanus lab!

Imagewhere RNA biology meets human disease

The McManus lab studies  fundamental processes relating to mammalian gene expression. We take high-throughput approaches, analyzing hundreds of thousands to millions of experiments at once, using complex libraries coupled to deep sequencing.  Our systems span from cell culture to in vivo models, focusing on a broad array of disease relevant tissues.  From cancer to diabetes, we develop novel technologies to help us better understand how genes are regulated and how they function in cells. This includes analysis of pathways and how genes interact in development and disease.  We aim to uncover the dark matter of the genome, shedding insight into the mysteries of noncoding RNA.

A major focus of the lab is on 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 function-based screening and other high-throughput methodologies to uncover gene function in the mammalian system.

Short and long noncoding RNAs. The McManus Lab uses high throughput systems to explore the biology of small (microRNAs) 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.