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Michael T. McManus

Bio: Michael T. McManus is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Gene silencing & Dicer. The author has an hindex of 65, co-authored 196 publications receiving 27123 citations. Previous affiliations of Michael T. McManus include University of California, Berkeley & Rancho Los Amigos National Rehabilitation Center.


Papers
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Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman2, Wouter Meuleman1, Jason Ernst3, Misha Bilenky4, Angela Yen2, Angela Yen1, Alireza Heravi-Moussavi4, Pouya Kheradpour2, Pouya Kheradpour1, Zhizhuo Zhang1, Zhizhuo Zhang2, Jianrong Wang1, Jianrong Wang2, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward1, Lucas D. Ward2, Abhishek Sarkar2, Abhishek Sarkar1, Gerald Quon2, Gerald Quon1, Richard Sandstrom7, Matthew L. Eaton2, Matthew L. Eaton1, Yi-Chieh Wu2, Yi-Chieh Wu1, Andreas R. Pfenning1, Andreas R. Pfenning2, Xinchen Wang2, Xinchen Wang1, Melina Claussnitzer1, Melina Claussnitzer2, Yaping Liu1, Yaping Liu2, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska2, Elizabeta Gjoneska1, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal1, Mukul S. Bansal2, Mukul S. Bansal10, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi1, Soheil Feizi2, Rosa Karlic11, Ah Ram Kim2, Ah Ram Kim1, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak2, Paz Polak15, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari1, Richard C Sallari2, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong1, Nicholas A Sinnott-Armstrong2, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager2, Philip L. De Jager15, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev2, Shamil R. Sunyaev15, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai1, Li-Huei Tsai2, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein2, Bradley E. Bernstein6, Bradley E. Bernstein15, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis2, Manolis Kellis1 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

Journal ArticleDOI
TL;DR: It is shown that lentivirus-delivered shRNAs are capable of specific, highly stable and functional silencing of gene expression in a variety of cell types and also in transgenic mice.
Abstract: RNA interference (RNAi) has recently emerged as a specific and efficient method to silence gene expression in mammalian cells either by transfection of short interfering RNAs (siRNAs; ref. 1) or, more recently, by transcription of short hairpin RNAs (shRNAs) from expression vectors and retroviruses. But the resistance of important cell types to transduction by these approaches, both in vitro and in vivo, has limited the use of RNAi. Here we describe a lentiviral system for delivery of shRNAs into cycling and non-cycling mammalian cells, stem cells, zygotes and their differentiated progeny. We show that lentivirus-delivered shRNAs are capable of specific, highly stable and functional silencing of gene expression in a variety of cell types and also in transgenic mice. Our lentiviral vectors should permit rapid and efficient analysis of gene function in primary human and animal cells and tissues and generation of animals that show reduced expression of specific genes. They may also provide new approaches for gene therapy.

1,690 citations

Journal ArticleDOI
TL;DR: This work has shown that the use of siRNAs to silence genes in vertebrate cells was only reported a year ago, and the emerging literature indicates that most vertebrate genes can be studied with this technology.
Abstract: Among the 3 billion base pairs of the human genome, there are approximately 30,000-40,000 protein-coding genes, but the function of at least half of them remains unknown. A new tool - short interfering RNAs (siRNAs) - has now been developed for systematically deciphering the functions and interactions of these thousands of genes. siRNAs are an intermediate of RNA interference, the process by which double-stranded RNA silences homologous genes. Although the use of siRNAs to silence genes in vertebrate cells was only reported a year ago, the emerging literature indicates that most vertebrate genes can be studied with this technology.

1,620 citations

Journal ArticleDOI
20 Apr 2007-Cell
TL;DR: It is shown that miRNA biogenesis in the mouse heart is essential for cardiogenesis, and targeted deletion of the muscle-specific miRNA, miR-1-2, revealed numerous functions in the heart, including regulation of cardiac morphogenesis, electrical conduction, and cell-cycle control.

1,420 citations

Journal ArticleDOI
12 Aug 2005-Science
TL;DR: It is reported that a 14-3-3–binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2- dependent gene transcription while repressing PPARγ-dependent gene transcription, indicating that TAZ functions as a molecular rheostat that modulates MSC differentiation.
Abstract: Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPARgamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPARgamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.

956 citations


Cited by
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TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Abstract: MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

6,345 citations

Journal Article
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Abstract: MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

6,306 citations

Journal ArticleDOI
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Abstract: MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.

6,282 citations

Journal Article
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Abstract: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.

6,064 citations

Journal ArticleDOI
21 Mar 2013-Nature
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Abstract: Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

5,922 citations