welcome to the mcmanus lab!

The McManus lab uses systematic and synthetic approaches to study fundamental processes relating to the regulation of gene function. We operate in a diversity of research areas- including RNA biology and developing cutting-edge research tools to answer fundamental biological questions. We take high-throughput approaches, analyzing hundreds of thousands to millions of experiments at once, using unique and 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.  We aim to uncover the dark matter of the genome, to help unravel the beautiful genomic complexity of pathways and how genes interact in development and disease. We develop new technologies to address unmet challenges and advance science in leaps and bounds through collaboration. 

Systematically deconvoluting molecular networks of genes. 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. Life depends on genetically encoded networks to help make sophisticated decisions influenced by the environment. Our studies add significantly to our understanding of how cells react to their environments and will shed new insight into genomic dark matter.

Quantitative models for studying gene regulation. Although the genome has been sequenced, there remains a lot of mystery about its content.  Our lab is interested in understanding how genes contribute to the specification of cell fate and function, and how deregulation by mutations of epigenetic alteration contributes to human disease. There is a big future for the study of genetics and molecular biology- particularly as genome deep sequencing technology matures and personalized medicine becomes a reality.  

Applying systems biology approaches to human disease models. Our group contains outstanding scientists from highly diverse fields including developmental biology, immunology, neurobiology, cancer, and biophysics. The diversity of our research areas reflects the freedom each trainee has to explore his/her passions and the open collaborative spirit of the lab. In the broadest sense possible, we apply high-throuput systems/synthetic biology approaches to fundamental problems in health and disease.  If you enjoy performing cutting-edge interdisciplinary research in an exciting and highly collaborative environment, please apply to our lab.  

Click on the below links to see some of our active projects.



Highlighted Recent Publications

High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.

Mues, Marsilius, Laila Karra, Damia Romero-Moya, Anica Wandler, Matthew J. Hangauer, Olga Ksionda, Yvonne Thus, Marthe Lindenbergh, Kevin Shannon, Michael T. McManus et al. In Cell Rep. Vol. 27. Cell Rep 27., 2019.

Dual gene activation and knockout screen reveals directional dependencies in genetic networks.

Boettcher, Michael, Ruilin Tian, James A. Blau, Evan Markegard, Ryan T. Wagner, David Wu, Xiulei Mo, Anne Biton, Noah Zaitlen, Haian Fu et al. In Nat Biotechnol. Nat. Biotechnol., 2018.

Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.

Hangauer, Matthew J., Vasanthi S. Viswanathan, Matthew J. Ryan, Dhruv Bole, John K. Eaton, Alexandre Matov, Jacqueline Galeas, Harshil D. Dhruv, Michael E. Berens, Stuart L. Schreiber et al. In Nature. Nature., 2017.