David E Root

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. ncbi request reprint Genome-scale loss-of-function screening with a lentiviral RNAi library
    David E Root
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nat Methods 3:715-9. 2006
  2. pmc Genome-scale CRISPR-Cas9 knockout screening in human cells
    Ophir Shalem
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Science 343:84-7. 2014
  3. pmc ATARiS: computational quantification of gene suppression phenotypes from multisample RNAi screens
    Diane D Shao
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Genome Res 23:665-78. 2013
  4. pmc A melanocyte lineage program confers resistance to MAP kinase pathway inhibition
    Cory M Johannessen
    1 The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA 2 Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA 3 Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
    Nature 504:138-42. 2013
  5. pmc MicroSCALE screening reveals genetic modifiers of therapeutic response in melanoma
    Kris C Wood
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Sci Signal 5:rs4. 2012
  6. pmc A public genome-scale lentiviral expression library of human ORFs
    Xiaoping Yang
    RNA interference RNAi Platform, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Methods 8:659-61. 2011
  7. doi request reprint Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers
    Joseph Rosenbluh
    Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
    Cell Syst 3:302-316.e4. 2016
  8. pmc Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4
    Yin Ren
    Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Sci Transl Med 4:147ra112. 2012
  9. pmc lincRNAs act in the circuitry controlling pluripotency and differentiation
    Mitchell Guttman
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 477:295-300. 2011
  10. pmc Systematic discovery of TLR signaling components delineates viral-sensing circuits
    Nicolas Chevrier
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Cell 147:853-67. 2011

Detail Information

Publications36

  1. ncbi request reprint Genome-scale loss-of-function screening with a lentiviral RNAi library
    David E Root
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nat Methods 3:715-9. 2006
    ..Initial screening efforts have demonstrated that these libraries and methods are practical and powerful tools for high-throughput lentivirus RNAi screens...
  2. pmc Genome-scale CRISPR-Cas9 knockout screening in human cells
    Ophir Shalem
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Science 343:84-7. 2014
    ..We observe a high level of consistency between independent guide RNAs targeting the same gene and a high rate of hit confirmation, demonstrating the promise of genome-scale screening with Cas9. ..
  3. pmc ATARiS: computational quantification of gene suppression phenotypes from multisample RNAi screens
    Diane D Shao
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Genome Res 23:665-78. 2013
    ..ATARiS is publicly available at http://broadinstitute.org/ataris...
  4. pmc A melanocyte lineage program confers resistance to MAP kinase pathway inhibition
    Cory M Johannessen
    1 The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA 2 Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA 3 Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
    Nature 504:138-42. 2013
    ..Collectively, these data suggest that oncogenic dysregulation of a melanocyte lineage dependency can cause resistance to RAF-MEK-ERK inhibition, which may be overcome by combining signalling- and chromatin-directed therapeutics. ..
  5. pmc MicroSCALE screening reveals genetic modifiers of therapeutic response in melanoma
    Kris C Wood
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Sci Signal 5:rs4. 2012
    ....
  6. pmc A public genome-scale lentiviral expression library of human ORFs
    Xiaoping Yang
    RNA interference RNAi Platform, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Methods 8:659-61. 2011
    ..Using this ORFeome resource, we created a genome-scale expression collection in a lentiviral vector, thereby enabling both targeted experiments and high-throughput screens in diverse cell types...
  7. doi request reprint Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers
    Joseph Rosenbluh
    Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
    Cell Syst 3:302-316.e4. 2016
    ....
  8. pmc Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4
    Yin Ren
    Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Sci Transl Med 4:147ra112. 2012
    ..These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets...
  9. pmc lincRNAs act in the circuitry controlling pluripotency and differentiation
    Mitchell Guttman
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 477:295-300. 2011
    ..Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state...
  10. pmc Systematic discovery of TLR signaling components delineates viral-sensing circuits
    Nicolas Chevrier
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Cell 147:853-67. 2011
    ..Our study illustrates the power of combining systematic measurements and perturbations to elucidate complex signaling circuits and discover potential therapeutic targets...
  11. pmc The bromodomain protein Brd4 insulates chromatin from DNA damage signalling
    Scott R Floyd
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 498:246-50. 2013
    ..These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage...
  12. pmc High-throughput Phenotyping of Lung Cancer Somatic Mutations
    Alice H Berger
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 30:214-28. 2016
    ....
  13. pmc MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
    Gregory V Kryukov
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Science 351:1214-8. 2016
    ..Together, our findings reveal PRMT5 as a potential vulnerability across multiple cancer lineages augmented by a common "passenger" genomic alteration. ..
  14. ncbi request reprint A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen
    Jason Moffat
    Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA
    Cell 124:1283-98. 2006
    ..This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery...
  15. pmc A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection
    Sagi D Shapira
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Cell 139:1255-67. 2009
    ..This multilayered approach provides a comprehensive and unbiased physical and regulatory model of influenza-host interactions and demonstrates a general strategy for uncovering complex host-pathogen relationships...
  16. pmc Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways
    Michelle Dang
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 110:9776-81. 2013
    ..Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease...
  17. pmc Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
    Richard Possemato
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 476:346-50. 2011
    ....
  18. pmc COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
    Cory M Johannessen
    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 468:968-72. 2010
    ....
  19. pmc Creation of Novel Protein Variants with CRISPR/Cas9-Mediated Mutagenesis: Turning a Screening By-Product into a Discovery Tool
    Katherine F Donovan
    Broad Institute of MIT and Harvard, Cambridge, MA, United States of America
    PLoS ONE 12:e0170445. 2017
    ....
  20. pmc Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies
    Glenn S Cowley
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Sci Data 1:140035. 2014
    ..g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features. ..
  21. pmc A functional landscape of resistance to ALK inhibition in lung cancer
    Frederick H Wilson
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Cancer Cell 27:397-408. 2015
    ....
  22. pmc Highly parallel identification of essential genes in cancer cells
    Biao Luo
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:20380-5. 2008
    ....
  23. pmc Receptor tyrosine kinases fall into distinct classes based on their inferred signaling networks
    Joel P Wagner
    Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Sci Signal 6:ra58. 2013
    ..Thus, classifying RTKs by their inferred networks and then therapeutically targeting multiple receptors within a class may delay or prevent the onset of resistance. ..
  24. pmc Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants
    Lisa Brenan
    The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Cell Rep 17:1171-1183. 2016
    ..This approach articulates an allele-characterization framework that can be scaled to meet the goals of genome-guided oncology...
  25. doi request reprint A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation
    Jason D Arroyo
    Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Cell Metab . 2016
    ..Our work yields a rich catalog of genes required for OXPHOS and, more generally, demonstrates the power of death screening for functional genomic analysis...
  26. doi request reprint High-Throughput Platform for Identifying Molecular Factors Involved in Phenotypic Stabilization of Primary Human Hepatocytes In Vitro
    Jing Shan
    Harvard MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA
    J Biomol Screen 21:897-911. 2016
    ....
  27. pmc Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles
    Eejung Kim
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
    Cancer Discov 6:714-26. 2016
    ..Because alleles found to be mutated only once in 5,338 tumors rendered cells tumorigenic, these observations underscore the value of integrating genomic information with functional studies...
  28. pmc Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst
    Daniel B Graham
    1 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA 2 Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Commun 6:7838. 2015
    ..Consequently, ablation of Rnf145 in murine macrophages enhances bacterial clearance, and rescues the oxidative burst defects associated with Ncf4 haploinsufficiency. ..
  29. pmc Resources for the design of CRISPR gene editing experiments
    Daniel B Graham
    Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
    Genome Biol 16:260. 2015
    ..Here, we review the key considerations in the design of genome editing experiments, and survey the tools and resources currently available to assist users of this technology...
  30. pmc Identification of an oncogenic RAB protein
    Douglas B Wheeler
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center MSKCC, New York, NY 10065, USA Weill Cornell Rockefeller University Sloan Kettering Tri Institutional MD PhD Program, New York, NY 10021, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Science 350:211-7. 2015
    ....
  31. pmc Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington's disease
    Reut Shema
    The Broad Institute of MIT and Harvard University, Cambridge, MA 02142 The Picower Institute for Learning and Memory, Cambridge, MA 02139 and
    Proc Natl Acad Sci U S A 112:268-72. 2015
    ....
  32. pmc KRAS and YAP1 converge to regulate EMT and tumor survival
    Diane D Shao
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Cell 158:171-84. 2014
    ..Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling. ..
  33. pmc ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state
    Yakov Chudnovsky
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Cell Rep 6:313-24. 2014
    ..These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state. ..
  34. pmc Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses
    Ido Amit
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Science 326:257-63. 2009
    ..This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells...
  35. pmc Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learning
    Thouis R Jones
    The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 106:1826-31. 2009
    ..By using this approach, we successfully scored images in RNA interference screens in 2 organisms for the prevalence of 15 diverse cellular morphologies, some of which were previously intractable...
  36. ncbi request reprint Integrative genomic approaches identify IKBKE as a breast cancer oncogene
    Jesse S Boehm
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell 129:1065-79. 2007
    ..These observations suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF-kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery...