Susan Lindquist

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. pmc Chemical and biological approaches for adapting proteostasis to ameliorate protein misfolding and aggregation diseases: progress and prognosis
    Susan L Lindquist
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA
    Cold Spring Harb Perspect Biol 3:. 2011
  2. pmc HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models
    Luke Whitesell
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Proc Natl Acad Sci U S A 111:18297-302. 2014
  3. pmc Mechanisms of protein-folding diseases at a glance
    Julie S Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dis Model Mech 7:9-14. 2014
  4. pmc BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis
    Allen W Bryan
    Harvard MIT Division of Health Science and Technology, Bioinformatics and Integrative Genomics, Cambridge, Massachusetts, USA
    PLoS Comput Biol 5:e1000333. 2009
  5. doi request reprint Protein folding sculpting evolutionary change
    S Lindquist
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cold Spring Harb Symp Quant Biol 74:103-8. 2009
  6. pmc Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson's disease models
    Linhui Julie Su
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dis Model Mech 3:194-208. 2010
  7. pmc Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity
    Martin L Duennwald
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Genes Dev 22:3308-19. 2008
  8. pmc Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:13626-31. 2008
  9. pmc Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation
    Jens Tyedmers
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:8633-8. 2010
  10. pmc Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons
    Daniel F Tardiff
    Whitehead Institute for Biomedical Research WIBR, Cambridge, MA 02142, USA
    Science 342:979-83. 2013

Detail Information

Publications83

  1. pmc Chemical and biological approaches for adapting proteostasis to ameliorate protein misfolding and aggregation diseases: progress and prognosis
    Susan L Lindquist
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA
    Cold Spring Harb Perspect Biol 3:. 2011
    ..We finish with evidence that synergy is achieved with the combination of mechanistically distinct approaches to reestablish organismal proteostasis...
  2. pmc HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models
    Luke Whitesell
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Proc Natl Acad Sci U S A 111:18297-302. 2014
    ..At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics. ..
  3. pmc Mechanisms of protein-folding diseases at a glance
    Julie S Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dis Model Mech 7:9-14. 2014
    ..In each case, we will highlight current therapeutic options for battling such diseases. ..
  4. pmc BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis
    Allen W Bryan
    Harvard MIT Division of Health Science and Technology, Bioinformatics and Integrative Genomics, Cambridge, Massachusetts, USA
    PLoS Comput Biol 5:e1000333. 2009
    ..BETASCAN is publicly accessible on the Web at http://betascan.csail.mit.edu...
  5. doi request reprint Protein folding sculpting evolutionary change
    S Lindquist
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cold Spring Harb Symp Quant Biol 74:103-8. 2009
    ..The multiple mechanisms by which protein folding can influence the evolution of new traits provide both a new paradigm for understanding rapid, stepwise evolution and a framework for targeted therapeutic interventions...
  6. pmc Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson's disease models
    Linhui Julie Su
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dis Model Mech 3:194-208. 2010
    ..Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD...
  7. pmc Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity
    Martin L Duennwald
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Genes Dev 22:3308-19. 2008
    ..Our results establish that impaired ER protein homeostasis is a broad and highly conserved contributor to polyQ toxicity in yeast, in PC12 cells, and, importantly, in striatal cells expressing full-length polyQ-expanded huntingtin...
  8. pmc Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:13626-31. 2008
    ..Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease...
  9. pmc Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation
    Jens Tyedmers
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:8633-8. 2010
    ..Thus, formation of the genetically transmissible prion state is a two-step process that involves an ancient system for the asymmetric inheritance of damaged proteins and heritable changes in the extent of prion fragmentation...
  10. pmc Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons
    Daniel F Tardiff
    Whitehead Institute for Biomedical Research WIBR, Cambridge, MA 02142, USA
    Science 342:979-83. 2013
    ..Thus, NAB identifies a druggable node in the biology of α-syn that can correct multiple aspects of its underlying pathology, including dysfunctional endosomal and endoplasmic reticulum-to-Golgi vesicle trafficking. ..
  11. pmc Conserved features of intermediates in amyloid assembly determine their benign or toxic states
    Rajaraman Krishnan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 109:11172-7. 2012
    ..Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike...
  12. pmc Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
    Sebastian Treusch
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 334:1241-5. 2011
    ..Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system...
  13. doi request reprint Epigenetics in the extreme: prions and the inheritance of environmentally acquired traits
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 330:629-32. 2010
    ..With intimate ties to protein homeostasis and a remarkable sensitivity to stress, prions are a robust mechanism that links environmental extremes with the acquisition and inheritance of new traits...
  14. pmc Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities
    James Shorter
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Mol Cell 23:425-38. 2006
    ..In vivid distinction, the endpoint of Ure2 fragmentation is short prion fibers with enhanced infectivity and self-replicating ability. These advances explain the distinct effects of Hsp104 on the inheritance of the two prions...
  15. doi request reprint Context-dependent perturbation of neural systems in transgenic mice expressing a cytosolic prion protein
    Henryk Faas
    Frances Bitter Magnet Laboratory, Massachusetts Institute of Technology, 150 Albany St, NW14 2213, Cambridge, MA 02139, USA
    Neuroimage 49:2607-17. 2010
    ....
  16. pmc Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast and animal models
    Joshua A Kritzer
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Chem Biol 5:655-63. 2009
    ..This work highlights the speed and efficiency of using libraries of expressed cyclic peptides for forward chemical genetics in cellular models of human disease...
  17. ncbi request reprint Inhibiting the transcription factor HSF1 as an anticancer strategy
    Luke Whitesell
    Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Expert Opin Ther Targets 13:469-78. 2009
    ..The malignant lifestyle confers dependence on this 'non-oncogene', suggesting a therapeutic role for HSF1 inhibitors...
  18. pmc Prion recognition elements govern nucleation, strain specificity and species barriers
    Peter M Tessier
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 447:556-61. 2007
    ..Thus, critical aspects of prion conversion are enciphered by subtle differences between small, highly specific recognition elements...
  19. pmc A systematic survey identifies prions and illuminates sequence features of prionogenic proteins
    Simon Alberti
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 137:146-58. 2009
    ..The self-perpetuating states of these proteins present a vast source of heritable phenotypic variation that increases the adaptability of yeast populations to diverse environments...
  20. pmc Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Mol Cell 43:72-84. 2011
    ..Molecular simulations focusing on intrinsic folding differences between Qs and Ns suggest that their different behaviors are due to the enhanced turn-forming propensity of Ns over Qs...
  21. pmc Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases
    Walker S Jackson
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 110:14759-64. 2013
    ..We conclude that single codon differences in a single gene in an otherwise normal genome can cause remarkably different neurodegenerative diseases and are sufficient to create distinct protein-based infectious elements. ..
  22. pmc Prions are a common mechanism for phenotypic inheritance in wild yeasts
    Randal Halfmann
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 482:363-8. 2012
    ..Fully one-third of wild strains harboured them. These, too, created diverse, often beneficial phenotypes. Thus, prions broadly govern heritable traits in nature, in a manner that could profoundly expand adaptive opportunities...
  23. pmc Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity
    Aaron D Gitler
    Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA
    Nat Genet 41:308-15. 2009
    ..Finally, we show that additional genes from our yeast screen, with diverse functions, are potent modifiers of alpha-syn-induced neuron loss in animals, establishing a diverse, highly conserved interaction network for alpha-syn...
  24. pmc Prions, protein homeostasis, and phenotypic diversity
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA, USA
    Trends Cell Biol 20:125-33. 2010
    ..In this article, we suggest that these qualities allow prions to act as 'bet-hedging' devices that facilitate the adaptation of yeasts to stressful environments, and might speed the evolution of new traits...
  25. ncbi request reprint Inhibiting GPI anchor biosynthesis in fungi stresses the endoplasmic reticulum and enhances immunogenicity
    Catherine A McLellan
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    ACS Chem Biol 7:1520-8. 2012
    ..Gwt1 is a promising antifungal drug target, and gepanacin is a useful probe for studying how disrupting GPI-anchor synthesis impairs viability and alters host-pathogen interactions in genetically intractable fungi...
  26. pmc Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis
    Chengkai Dai
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Clin Invest 122:3742-54. 2012
    ..The loss of NF1 function engages an evolutionarily conserved cellular survival mechanism that ultimately impairs survival of the whole organism by facilitating carcinogenesis...
  27. pmc Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells
    Mikko Taipale
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 31:630-7. 2013
    ....
  28. pmc Clioquinol promotes the degradation of metal-dependent amyloid-β (Aβ) oligomers to restore endocytosis and ameliorate Aβ toxicity
    Kent E S Matlack
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Proc Natl Acad Sci U S A 111:4013-8. 2014
    ..Establishing the ability of the Aβ yeast model to identify disease-relevant compounds supports its further exploitation as a validated early discovery platform. ..
  29. pmc Overcoming fluconazole resistance in Candida albicans clinical isolates with tetracyclic indoles
    Willmen Youngsaye
    Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 22:3362-5. 2012
    ..albicans, as determined in Saccharomyces cerevisiae models, and may be a useful probe to uncover alternative resistance pathways...
  30. pmc Flanking sequences profoundly alter polyglutamine toxicity in yeast
    Martin L Duennwald
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 103:11045-50. 2006
    ..Very tight aggregates always are benign, whereas amorphous aggregates can be toxic. We thereby establish a previously undescribed systematic characterization of the influence of flanking amino acid sequences on polyQ toxicity...
  31. pmc Physical properties of polymorphic yeast prion amyloid fibers
    Carlos E Castro
    Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Biophys J 101:439-48. 2011
    ..Thermal fluctuation analysis confirmed the twofold difference in persistence length between S[PSI(+)] and W[PSI(+)] fibers and revealed a torsional stiffness of kinks and cross-links of ~100-200 pN·nm/rad...
  32. pmc The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration
    Danica Chen
    Department of Biology, MIT, Cambridge, MA 02139, USA
    Exp Gerontol 43:1086-93. 2008
    ..Taken together, our results suggest a more complex interplay between CR, SIRT1, and neurodegenerative diseases than previously appreciated...
  33. pmc Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity
    Esti Yeger-Lotem
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Genet 41:316-23. 2009
    ..Bridging these data and data from mRNA profiling provided functional explanations for many of these genes and identified previously unknown relations between alpha-synuclein toxicity and basic cellular pathways...
  34. pmc The prion protein knockout mouse: a phenotype under challenge
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Prion 1:83-93. 2007
    ..The critical question remains open: which of these phenotypes are primary effects of PrP deletion and what do they tell us about the function of PrP?..
  35. pmc Context dependent neuroprotective properties of prion protein (PrP)
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, MIT, Cambridge, MA, USA
    Prion 3:240-9. 2009
    ..These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein...
  36. pmc Prion pathogenesis is independent of caspase-12
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Massachusets Institute of Technology, Cambridge Massachusetts 02142, USA
    Prion 1:243-7. 2007
    ....
  37. pmc TorsinA and the torsinA-interacting protein printor have no impact on endoplasmic reticulum stress or protein trafficking in yeast
    Julie S Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America
    PLoS ONE 6:e22744. 2011
    ..Alternatively, torsinA may not function in endoplasmic reticulum protein homeostasis. The strains and assays we describe may provide useful tools for identifying and investigating these possibilities and are freely available...
  38. pmc Diminishing apoptosis by deletion of Bax or overexpression of Bcl-2 does not protect against infectious prion toxicity in vivo
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    J Neurosci 27:13022-7. 2007
    ..These results suggest that Bax and Bcl-2 mediated apoptotic pathways are not the major contributing factor to the clinical or pathological features of infectious prion disease...
  39. pmc Prion switching in response to environmental stress
    Jens Tyedmers
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    PLoS Biol 6:e294. 2008
    ..These findings support the hypothesis that [PSI(+)] is a mechanism to increase survival in fluctuating environments and might function as a capacitor to promote evolvability...
  40. pmc Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice
    Walker S Jackson
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Neuron 63:438-50. 2009
    ..Thus, a single amino acid change in PrP is sufficient to induce a distinct neurodegenerative disease and the spontaneous generation of prion infectivity...
  41. pmc A method for probing the mutational landscape of amyloid structure
    Charles W O'Donnell
    Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139, USA
    Bioinformatics 27:i34-42. 2011
    ..Experimental structure determination has proven extremely difficult with only a handful of NMR-based models proposed, suggesting a need for computational methods...
  42. pmc Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons
    Chee Yeun Chung
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 342:983-7. 2013
    ..A small molecule identified in a yeast screen (NAB2), and the ubiquitin ligase Nedd4 it affects, reversed pathologic phenotypes in these neurons. ..
  43. pmc Genetic architecture of Hsp90-dependent drug resistance
    Leah E Cowen
    Whitehead Institute, Nine Cambridge Center, Cambridge, MA 02142, USA
    Eukaryot Cell 5:2184-8. 2006
    ..Here, we explored effectors downstream of calcineurin regulating this Hsp90-dependent trait. Using S. cerevisiae erg3 mutants as a model, we determined that both Crz1 and Hph1 modulate azole resistance...
  44. pmc Probing the role of PrP repeats in conformational conversion and amyloid assembly of chimeric yeast prions
    Jijun Dong
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    J Biol Chem 282:34204-12. 2007
    ..It also reveals new features of the yeast prion protein, and provides a level of control over yeast prion assembly that will be useful for future structural studies and for creating amyloid-based biomaterials...
  45. pmc A heritable switch in carbon source utilization driven by an unusual yeast prion
    Jessica C S Brown
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Genes Dev 23:2320-32. 2009
    ....
  46. pmc Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, 02142, USA
    Proc Natl Acad Sci U S A 103:3416-21. 2006
    ..Because the final number of neurons produced in the DG is unchanged by PrP(c) expression, other factors must control the ultimate fate of new neurons...
  47. pmc Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis
    Chengkai Dai
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 130:1005-18. 2007
    ..While it enhances organismal survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer...
  48. pmc Optical trapping with high forces reveals unexpected behaviors of prion fibrils
    Jijun Dong
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Struct Mol Biol 17:1422-30. 2010
    ..Thus, our results reveal unusually strong noncovalent intermolecular contacts that maintain fibril integrity even when individual monomers partially unfold and extend fibril length...
  49. pmc Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms
    Daniel F Tardiff
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 287:4107-20. 2012
    ..Our unbiased identification of 8-OHQs in a yeast TDP-43 toxicity model suggests that tailoring 8-OHQ activity to a particular neurodegenerative disease may be a viable therapeutic strategy...
  50. pmc HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers
    Marc L Mendillo
    The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 150:549-62. 2012
    ..Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications...
  51. pmc Amyloid deposits: protection against toxic protein species?
    Sebastian Treusch
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell Cycle 8:1668-74. 2009
    ..Furthermore, we discuss how exceeding the cellular capacity for protective deposition of misfolded proteins may contribute to the formation of toxic protein species...
  52. pmc Fitness trade-offs restrict the evolution of resistance to amphotericin B
    Benjamin Matteson Vincent
    Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America
    PLoS Biol 11:e1001692. 2013
    ..Developing antibiotics that deliberately create such evolutionary constraints might offer a strategy for limiting the rapid emergence of drug resistance. ..
  53. pmc Splice isoform and pharmacological studies reveal that sterol depletion relocalizes α-synuclein and enhances its toxicity
    Julie S Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Proc Natl Acad Sci U S A 111:3014-9. 2014
    ....
  54. doi request reprint Blessings in disguise: biological benefits of prion-like mechanisms
    Gregory A Newby
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Trends Cell Biol 23:251-9. 2013
    ..Here, we discuss several PriLiMs and their functions, intending to spur discussion and collaboration on the subject of beneficial prion-like behaviors...
  55. pmc Widespread regulation of translation by elongation pausing in heat shock
    Reut Shalgi
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell 49:439-52. 2013
    ..Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses...
  56. pmc Prion formation by a yeast GLFG nucleoporin
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA, USA
    Prion 6:391-9. 2012
    ..Furthermore, we demonstrate that Nup100 can form bona fide prions, thus establishing a previously undiscovered ability of yeast GLFG nucleoporins to adopt this conformational state in vivo...
  57. pmc A network of protein interactions determines polyglutamine toxicity
    Martin L Duennwald
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 103:11051-6. 2006
    ....
  58. ncbi request reprint Prions as adaptive conduits of memory and inheritance
    James Shorter
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Nat Rev Genet 6:435-50. 2005
    ..We then describe situations in which prion-enciphered events might have essential roles in long-term memory formation, transcriptional memory and genome-wide expression patterns...
  59. ncbi request reprint Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers
    James Shorter
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 304:1793-7. 2004
    ..These Hsp104 activities differed in their reaction mechanism and can explain [PSI+] inheritance patterns...
  60. pmc The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy
    Ruth Scherz-Shouval
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 158:564-78. 2014
    ..Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications. ..
  61. pmc The Parkinson's disease protein alpha-synuclein disrupts cellular Rab homeostasis
    Aaron D Gitler
    Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:145-50. 2008
    ..Thus, alpha-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive...
  62. pmc An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component
    Sebastian Treusch
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    J Cell Biol 197:369-79. 2012
    ..Our work illustrates how the promiscuous interactions of an intrinsically disordered protein can produce highly specific cellular toxicities through illicit, yet highly specific, interactions with the proteome...
  63. doi request reprint Biochemical, cell biological, and genetic assays to analyze amyloid and prion aggregation in yeast
    Simon Alberti
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Methods Enzymol 470:709-34. 2010
    ..Here, we provide a range of biochemical, cell biological and yeast genetic methods that are currently used in our laboratory to study protein aggregation and the formation of amyloids and prions...
  64. pmc Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition
    Mikko Taipale
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 150:987-1001. 2012
    ..Our results establish HSP90 client recognition as a combinatorial process: CDC37 provides recognition of the kinase family, whereas thermodynamic parameters determine client binding within the family...
  65. pmc SIRT1 protects against α-synuclein aggregation by activating molecular chaperones
    Gizem Donmez
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Neurosci 32:124-32. 2012
    ..Thus, SIRT1 responds to α-synuclein aggregation-induced stress by activating molecular chaperones to protect against disease...
  66. doi request reprint HSP90 at the hub of protein homeostasis: emerging mechanistic insights
    Mikko Taipale
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 11:515-28. 2010
    ..Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions...
  67. pmc Hsp90 and environmental stress transform the adaptive value of natural genetic variation
    Daniel F Jarosz
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 330:1820-4. 2010
    ..This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes...
  68. pmc Protein-only mechanism induces self-perpetuating changes in the activity of neuronal Aplysia cytoplasmic polyadenylation element binding protein (CPEB)
    Sven U Heinrich
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:2999-3004. 2011
    ..These biochemical memories might be used in the local homeostatic maintenance of long-term learning-related changes in synaptic morphology and function...
  69. pmc Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody
    David W Colby
    Department of Chemical Engineering and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:17616-21. 2004
    ..The demonstrated importance of disulfide bond-independent binding for intrabody potency suggests a generally applicable approach to the development of effective intrabodies against other intracellular targets...
  70. ncbi request reprint Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi
    Leah E Cowen
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 309:2185-9. 2005
    ..During selection in a human host, drug resistance that was initially Hsp90-dependent evolved toward independence. Thus, Hsp90 can act in diverse ways to couple environmental contingency to the emergence and fixation of new traits...
  71. ncbi request reprint HSP90 and the chaperoning of cancer
    Luke Whitesell
    Steele Memorial Children s Research Center, University of Arizona, Tucson, Arizona 85724, USA
    Nat Rev Cancer 5:761-72. 2005
    ..Pharmacologically 'bribing' the essential guard duty of the chaperone HSP90 (heat-shock protein of 90 kDa) seems to offer a unique anticancer strategy of considerable promise...
  72. pmc Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolates
    Willmen Youngsaye
    Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Bioorg Med Chem Lett 21:5502-5. 2011
    ..A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria...
  73. doi request reprint Protein homeostasis and the phenotypic manifestation of genetic diversity: principles and mechanisms
    Daniel F Jarosz
    Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA
    Annu Rev Genet 44:189-216. 2010
    ....
  74. doi request reprint α-Synuclein: membrane interactions and toxicity in Parkinson's disease
    Pavan K Auluck
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Annu Rev Cell Dev Biol 26:211-33. 2010
    ..Finally, we present a model linking vesicle dynamics to toxicity with the sincere hope that understanding these disease mechanisms will lead to the development of novel, potent therapeutics...
  75. pmc Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations
    Frank Soldner
    The Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 146:318-31. 2011
    ..The robust capability to genetically correct disease-causing point mutations in patient-derived hiPSCs represents significant progress for basic biomedical research and an advance toward hiPSC-based cell replacement therapies...
  76. pmc The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington's and prion diseases
    Andrew D Steele
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 104:1983-8. 2007
    ..We devised a systems approach for multiple-parameter phenotypic characterization and applied it to defining disease onset robustly and at early time points...
  77. pmc Yeast cells provide insight into alpha-synuclein biology and pathobiology
    Tiago Fleming Outeiro
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 302:1772-5. 2003
    ..This readily manipulable system provides an opportunity to dissect the molecular pathways underlying normal alpha-synuclein biology and the pathogenic consequences of its misfolding...
  78. ncbi request reprint Under cover: causes, effects and implications of Hsp90-mediated genetic capacitance
    Todd A Sangster
    Whitehead Institute for Biomedical Research, Cambridge, MA, USA
    Bioessays 26:348-62. 2004
    ..A true understanding of evolutionary processes will require an integration of current evolutionary paradigms with the many new insights accruing in protein science...
  79. pmc Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal
    Cheng Cheng Zhang
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 103:2184-9. 2006
    ..Ectopic expression of PrP in PrP-null bone marrow cells by retroviral infection rescued the defective hematopoietic engraftment during serial transplantation. Therefore, PrP is a marker for HSCs and supports their self-renewal...
  80. pmc A suite of Gateway cloning vectors for high-throughput genetic analysis in Saccharomyces cerevisiae
    Simon Alberti
    Whitehead Institute for Biomedical Research, Cambridge, MA, USA
    Yeast 24:913-9. 2007
    ..We have made this yeast Gateway vector kit available to the research community via the non-profit Addgene Plasmid Repository (http://www.addgene.org/yeast_gateway)...
  81. ncbi request reprint Increase in activity during calorie restriction requires Sirt1
    Danica Chen
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Science 310:1641. 2005
    ..In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice...
  82. pmc A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104
    Anil G Cashikar
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02143, USA
    J Biol Chem 280:23869-75. 2005
    ..Hence, Hsp26 plays an important role in pathways that defend cells against environmental stress and the types of protein misfolding seen in neurodegenerative disease...