Michael Mcmanus, PhD

Diabetes Center
+1 415 476-4661
Research Overview: 

The McManus lab studies fundamental processes relating to the regulation of gene expression. We operate in a diversity of research areas- including RNA biology and developing cutting-edge research tools based on RNA biology— 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 coding and noncoding genes. 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. 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 noncoding RNA dark matter.

Quantitative models for studying gene regulation. Although the genome has been sequenced, there remains a lot of mystery about its content. To date only a handful of noncoding RNAs 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 fundamental 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. 

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. We are interested in applying high-throuput and systems/synthetic biology 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.  

Primary Thematic Area: 
Human Genetics
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Noncoding RNAs - the Dark Matter of the Genome



BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.


Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White PJ, McGarrah RW, Ilkayeva OR, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M, Ishikawa T, Kim K, Chen Y, Sponton CH, Pradhan RN, Majd H, Greiner VJ, Yoneshiro M, Brown Z, Chondronikola M, Takahashi H, Goto T, Kawada T, Sidossis L, Szoka FC, McManus MT, Saito M, Soga T, Kajimura S

Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons.

Cell reports

Lindtner S, Catta-Preta R, Tian H, Su-Feher L, Price JD, Dickel DE, Greiner V, Silberberg SN, McKinsey GL, McManus MT, Pennacchio LA, Visel A, Nord AS, Rubenstein JLR

miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival.

Cell reports

Gagnon JD, Kageyama R, Shehata HM, Fassett MS, Mar DJ, Wigton EJ, Johansson K, Litterman AJ, Odorizzi P, Simeonov D, Laidlaw BJ, Panduro M, Patel S, Jeker LT, Feeney ME, McManus MT, Marson A, Matloubian M, Sanjabi S, Ansel KM

Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area.


Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY

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

Cell reports

Mues M, Karra L, Romero-Moya D, Wandler A, Hangauer MJ, Ksionda O, Thus Y, Lindenbergh M, Shannon K, McManus MT, Roose JP