Research Topics
| David SabatiniSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
Research Grants
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Detail Information
Publications
Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKBDos D Sarbassov
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Mol Cell 22:159-68. 2006..Our work describes an unforeseen mechanism of action for rapamycin that suggests it can be used to inhibit Akt/PKB in certain cell types...
CellProfiler: image analysis software for identifying and quantifying cell phenotypesAnne E Carpenter
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Genome Biol 7:R100. 2006....- CellProfiler Analyst: data exploration and analysis software for complex image-based screensThouis R Jones
Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
BMC Bioinformatics 9:482. 2008..Image-based screens can produce hundreds of measured features for each of hundreds of millions of individual cells in a single experiment... - mTOR and cancer: insights into a complex relationshipDavid M Sabatini
Whitehead Institute for Biomedical Research, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142 1479, USA
Nat Rev Cancer 6:729-34. 2006..The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas... - Microarrays of lentiviruses for gene function screens in immortalized and primary cellsSteve N Bailey
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Methods 3:117-22. 2006..Because lentiviruses have a wide cellular tropism, including primary cells, lentivirus-infected cell microarrays can be used as a platform for high-throughput screening in a variety of cell types... - Lentivirus-delivered stable gene silencing by RNAi in primary cellsSheila A Stewart
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
RNA 9:493-501. 2003.... - Genome-scale loss-of-function screening with a lentiviral RNAi libraryDavid 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... - A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screenJason 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... - Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learningThouis 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... - Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeletonD D Sarbassov
Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
Curr Biol 14:1296-302. 2004..We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals... - Defining the role of mTOR in cancerDavid A Guertin
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02141, USA
Cancer Cell 12:9-22. 2007..We further discuss the use of rapamycin in oncology and conclude with a discussion on the future of mTOR-targeted therapy... - Systematic genome-wide screens of gene functionAnne E Carpenter
Whitehead Institute for Biomedical Research, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Rev Genet 5:11-22. 2004 - Highly parallel identification of essential genes in cancer cellsBiao 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.... - mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in miceDavid A Guertin
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cancer Cell 15:148-59. 2009..The selective requirement for mTORC2 in tumor development suggests that mTORC2 inhibitors may be of substantial clinical utility... - Off-target effects associated with long dsRNAs in Drosophila RNAi screensJason Moffat
Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
Trends Pharmacol Sci 28:149-51. 2007..Discovering multiple potent siRNAs with minimal off-target profiles for each target transcript will be invaluable for genome-based studies of gene function and for personalized RNAi therapeutics... - CellProfiler: free, versatile software for automated biological image analysisMichael R Lamprecht
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Biotechniques 42:71-5. 2007.... - mTOR and cancer: many loops in one pathwayAlejo Efeyan
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, United States
Curr Opin Cell Biol 22:169-76. 2010..Extensive research on mTOR has also uncovered a complex network of regulatory loops that impact the therapeutic approaches aimed at targeting mTOR... 
The pharmacology of mTOR inhibitionDavid A Guertin
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
Sci Signal 2:pe24. 2009..Here, we summarize exciting findings regarding mTOR signaling and the outlook for mTOR inhibitors as tools to study the mTOR pathway and as drugs in the clinic...- RNAi living-cell microarrays for loss-of-function screens in Drosophila melanogaster cellsDouglas B Wheeler
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Methods 1:127-32. 2004.... - Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screensSteve N Bailey
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 101:16144-9. 2004..This method will be useful to those performing small-molecule screens to discover new chemical tools and potential therapeutic agents... - Cell microarrays and RNA interference chip away at gene functionDouglas B Wheeler
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Genet 37:S25-30. 2005..Though still a budding technology, RNAi cell microarrays promise to increase the efficiency, economy and ease of genome-wide RNAi screens in metazoan cells... - Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complexDos D Sarbassov
Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
J Biol Chem 280:39505-9. 2005..Our findings suggest that a redox-based signaling mechanism may participate in regulating the nutrient-sensitive raptor-mTOR complex and pathway... - Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif siteSiraj M Ali
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, 02142, USA
J Biol Chem 280:19445-8. 2005..Because many members of the AGC family of kinases lack an analogous domain, rictor-mTOR may phosphorylate the hydrophobic motifs of other kinases... - Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complexD D Sarbassov
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
Science 307:1098-101. 2005..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation... - Growing roles for the mTOR pathwayDos D Sarbassov
Whitehead Institute, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachussetts 02142, USA
Curr Opin Cell Biol 17:596-603. 2005.... - An expanding role for mTOR in cancerDavid A Guertin
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02141, USA
Trends Mol Med 11:353-61. 2005..In this article, we re-evaluate mTOR signaling, suggesting a more central role for mTOR in cancers with defective PtdIns3K-PTEN signaling and conceptually discuss these implications in the context of drug discovery... - Cancer cell metabolism: Warburg and beyondPeggy P Hsu
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology Department of Biology, Cambridge, MA 02142, USA
Cell 134:703-7. 2008..In this Essay, we re-examine the Warburg effect and establish a framework for understanding its contribution to the altered metabolism of cancer cells... - Increased mTORC1 signaling UPRegulates stressJan H Reiling
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Mol Cell 29:533-5. 2008..2008) show that the loss of the tuberous sclerosis tumor suppressor complex induces endoplasmic reticulum stress, leading to attenuation of insulin receptor signaling activity via the unfolded protein response... - mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machineryDo Hyung Kim
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Cell 110:163-75. 2002..We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels... - Tumours with PI3K activation are resistant to dietary restrictionNada Y Kalaany
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 458:725-31. 2009..Thus, the PI3K pathway is an important determinant of the sensitivity of tumours to dietary restriction, and activating mutations in the pathway may influence the response of cancers to dietary restriction-mimetic therapies... - DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survivalTimothy R Peterson
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Cell 137:873-86. 2009..Thus, we identify a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival... - Growth signaling at the nexus of stem cell life and deathKris C Wood
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Cell Stem Cell 5:232-4. 2009..In this issue of Cell Stem Cell and in Nature, Castilho et al. (2009) and Harrison et al. (2009) highlight the importance of mTOR signaling in stem cell exhaustion and mammalian aging, respectively... - eIF3: a connecTOR of S6K1 to the translation preinitiation complexTim R Peterson
The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Mol Cell 20:655-7. 2005.... - PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinaseYasemin Sancak
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
Mol Cell 25:903-15. 2007..We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both... - Building mammalian signalling pathways with RNAi screensJason Moffat
Whitehead Institute, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Rev Mol Cell Biol 7:177-87. 2006..We are now at the brink of being able to harness the power of RNAi for large-scale functional discovery in mammalian cells... - Functional genomics identifies TOR-regulated genes that control growth and divisionDavid A Guertin
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Curr Biol 16:958-70. 2006..Moreover, this strategy, if applied in model systems with simpler genomes, can identify genes with conserved functions in mammals... - mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2sMaria A Frias
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Curr Biol 16:1865-70. 2006..Even though all mTORC2s can phosphorylate Akt/PKB in vitro, insulin regulates the activity of only two of them. Thus, we propose that cells contain several mTORC2 flavors that may phosphorylate Akt/PKB in response to different signals... - AMPK and p53 help cells through lean timesCarson C Thoreen
The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Cell Metab 1:287-8. 2005..Recent work by Jones and colleagues (Jones et al.,2005) reveals how the AMP-activated kinase mediates this process by phosphorylating and activating the tumor suppressor p53... - The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1Yasemin Sancak
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
Science 320:1496-501. 2008..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb... - GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTORDo Hyung Kim
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, 02142, USA
Mol Cell 11:895-904. 2003..Thus, we propose that the opposing effects on mTOR activity of the GbetaL- and raptor-mediated interactions regulate the mTOR pathway... - TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and functionStefanie S Schalm
The Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Curr Biol 13:797-806. 2003..However, it is unclear how the TOS motif in S6K1 and 4E-BP1 mediates mTOR signaling... - Minimizing the risk of reporting false positives in large-scale RNAi screensChristophe J Echeverri
Cenix BioScience GmbH, Tatzberg 47, Dresden, 10307, Germany
Nat Methods 3:777-9. 2006.... - Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AMLZhihong Zeng
Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
Blood 109:3509-12. 2007..Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo, and supports the therapeutic potential of mTOR inhibition strategies in leukemias... - Huntingtin aggregates ask to be eatenCarson C Thoreen
Nat Genet 36:553-4. 2004
Research Grants
- Rapamycin-Insensitive Signaling by Rictor-mTORDavid Sabatini; Fiscal Year: 2009..abstract_text> ..
- Regulation of the mTOR Pathway By NutrientsDavid Sabatini; Fiscal Year: 2009..We anticipate that our work will elucidate molecular mechanisms that may be deranged in human cancers and thus may serve as targets for future drug development. ..
- Cell Growth Signaling in Cancer DevelopmentDavid M Sabatini; Fiscal Year: 2010....
- Metabolism and Phosphatase Regulation of the TOR PathwayDavid Sabatini; Fiscal Year: 2007....
- Regulation of the mTOR growth pathway by nutrientsDavid Sabatini; Fiscal Year: 2007....
- TRANSLATIONAL CONTROL BY RAPAMYCIN-SENSITIVE SIGNALINGDavid Sabatini; Fiscal Year: 2004..Thus, our study of the RAFT1 signaling pathway will not only elucidate the workings of a critical regulator of cell division, but also explain how a clinically useful drug exerts its effects. ..
- Regulation of the mTOR Pathway By NutrientsDavid M Sabatini; Fiscal Year: 2010..Furthermore, some of the signaling mechanisms we uncover may serve in the future as targets for drug development. ..