Luke Whitesell

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. ncbi request reprint The anticancer activity of the fungal metabolite terrecyclic acid A is associated with modulation of multiple cellular stress response pathways
    Thomas J Turbyville
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, Tucson, AZ 85706 6800, USA
    Mol Cancer Ther 4:1569-76. 2005
  2. ncbi request reprint Actin microfilament aggregation induced by withaferin A is mediated by annexin II
    Ryan R Falsey
    Nat Chem Biol 2:33-8. 2006
  3. ncbi request reprint Inhibiting HSP90 to treat cancer: a strategy in evolution
    L Whitesell
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Mol Med 12:1108-24. 2012
  4. doi request reprint HSP90 as a platform for the assembly of more effective cancer chemotherapy
    Luke Whitesell
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Biochim Biophys Acta 1823:756-66. 2012
  5. 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
  6. 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
  7. pmc Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desert
    Thomas J Turbyville
    SW Center for Natural Products Research and Commercialization, University of Arizona, Tucson, Arizona 85706 6800, USA
    J Nat Prod 69:178-84. 2006
  8. ncbi request reprint Structure-activity relationships for withanolides as inducers of the cellular heat-shock response
    E M Kithsiri Wijeratne
    SW Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 East Valencia Road, Tucson, Arizona 85706, United States
    J Med Chem 57:2851-63. 2014
  9. 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
  10. 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

Collaborators

Detail Information

Publications35

  1. ncbi request reprint The anticancer activity of the fungal metabolite terrecyclic acid A is associated with modulation of multiple cellular stress response pathways
    Thomas J Turbyville
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, Tucson, AZ 85706 6800, USA
    Mol Cancer Ther 4:1569-76. 2005
    ..Small-molecule natural products such as TCA may serve as useful probes for understanding the relationships between these pathways, potentially providing leads for the design of novel and effective anticancer drugs...
  2. ncbi request reprint Actin microfilament aggregation induced by withaferin A is mediated by annexin II
    Ryan R Falsey
    Nat Chem Biol 2:33-8. 2006
    ....
  3. ncbi request reprint Inhibiting HSP90 to treat cancer: a strategy in evolution
    L Whitesell
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Mol Med 12:1108-24. 2012
    ..This review will focus on these fundamental issues with the goal of suggesting ways to make the clinical development of HSP90 inhibitors become less empiric and ultimately more successful...
  4. doi request reprint HSP90 as a platform for the assembly of more effective cancer chemotherapy
    Luke Whitesell
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Biochim Biophys Acta 1823:756-66. 2012
    ..This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90)...
  5. 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...
  6. 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...
  7. pmc Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desert
    Thomas J Turbyville
    SW Center for Natural Products Research and Commercialization, University of Arizona, Tucson, Arizona 85706 6800, USA
    J Nat Prod 69:178-84. 2006
    ..Isolation of radicicol and monocillin I in this study provides evidence that we have developed an effective strategy for discovering natural product-based Hsp90 inhibitors with potential anticancer activity...
  8. ncbi request reprint Structure-activity relationships for withanolides as inducers of the cellular heat-shock response
    E M Kithsiri Wijeratne
    SW Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 East Valencia Road, Tucson, Arizona 85706, United States
    J Med Chem 57:2851-63. 2014
    ....
  9. 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...
  10. 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...
  11. ncbi request reprint Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin
    Rochelle Bagatell
    Steele Memorial Children s Research Center and The Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
    Int J Cancer 113:179-88. 2005
    ..Our findings suggest that Hsp90 inhibitors may prove useful either alone or as a component of multi-drug regimens in the treatment of neuroblastoma and osteosarcoma...
  12. ncbi request reprint A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium globosum demonstrates anticancer activity
    E M Kithsiri Wijeratne
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, 250 E Valencia Road, Tucson, AZ 85706 6800, USA
    Bioorg Med Chem 14:7917-23. 2006
    ....
  13. 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...
  14. ncbi request reprint Altered Hsp90 function in cancer: a unique therapeutic opportunity
    Rochelle Bagatell
    Department of Pediatrics and Hematology Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
    Mol Cancer Ther 3:1021-30. 2004
    ....
  15. doi request reprint Synthesis and biological evaluation of novobiocin analogues as potential heat shock protein 90 inhibitors
    G M Kamal B Gunaherath
    Southwest Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, AZ 85706, United States
    Bioorg Med Chem 21:5118-29. 2013
    ..Our most potent new analogue 19 demonstrated biological activities consistent with known HSP90-binding agents, but with greater potency than NB. ..
  16. ncbi request reprint Isolation, optimization of production and structure-activity relationship studies of monocillin I, the cytotoxic constituent of Paraphaeosphaeria quadriseptata
    E M Kithsiri Wijeratne
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, Arizona 85706 6800, USA
    J Antibiot (Tokyo) 57:541-6. 2004
  17. pmc Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: structure-activity relationships of geopyxins and their analogues
    E M Kithsiri Wijeratne
    SW Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, Arizona 85706, United States
    J Nat Prod 75:361-9. 2012
    ....
  18. pmc A rhizosphere fungus enhances Arabidopsis thermotolerance through production of an HSP90 inhibitor
    Catherine A McLellan
    FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
    Plant Physiol 145:174-82. 2007
    ..Finally, cocultivation of P. quadriseptata with Arabidopsis enhanced plant heat stress tolerance. These data demonstrate that HSP90-inhibitory compounds produced by fungi can influence plant growth and responses to the environment...
  19. 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. ..
  20. 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...
  21. 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
    ....
  22. 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...
  23. ncbi request reprint Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study
    Rochelle Bagatell
    Department of Pediatrics and Steele Children s Research Center, University of Arizona, Tucson, AZ 85724, USA
    Clin Cancer Res 13:1783-8. 2007
    ....
  24. ncbi request reprint Ponicidin and oridonin are responsible for the antiangiogenic activity of Rabdosia rubescens, a constituent of the herbal supplement PC SPES
    Linda C Meade-Tollin
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, AZ 85706 6800, USA
    J Nat Prod 67:2-4. 2004
    ....
  25. doi request reprint 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera
    Ya ming Xu
    Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, 250 E Valencia Road, Tucson, AZ 85706, USA
    Bioorg Med Chem 17:2210-4. 2009
    ....
  26. ncbi request reprint Heat shock protein 90: a unique chemotherapeutic target
    Sara B Cullinan
    The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Semin Oncol 33:457-65. 2006
    ..In this review, we highlight the current understanding of Hsp90 biology as it relates to cancer and discuss the discovery, development, and clinical status of Hsp90 inhibitors as anticancer drugs...
  27. ncbi request reprint HSP90: a rising star on the horizon of anticancer targets
    Chengkai Dai
    Whitehead Institute for Biomedical Research, Room 649, 9 Cambridge Center, Cambridge, MA 02142, and University of Arizona, Steele Memorial Children s Research Center, Tucson, AZ 85724, USA
    Future Oncol 1:529-40. 2005
    ..Finally, it closes with a discussion of the unique challenges confronting the further development of these agents and their prospects for the future...
  28. ncbi request reprint Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert
    E M Kithsiri Wijeratne
    SW Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, Arizona 85706 6800, USA
    J Nat Prod 66:1567-73. 2003
    ..A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed...
  29. ncbi request reprint The stress response: implications for the clinical development of hsp90 inhibitors
    Luke Whitesell
    Steele Memorial Children s Research Center, University of Arizona, Tucson, AZ 85724, USA
    Curr Cancer Drug Targets 3:349-58. 2003
    ..Lastly, stress response induction by Hsp90 inhibitors may have therapeutic benefits in non-neoplastic disorders such as heart disease, stroke and neurodegenerative diseases. These benefits are just beginning to be explored...
  30. 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...
  31. ncbi request reprint Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors
    Jason Beliakoff
    Steele Memorial Children s Research Center, University of Arizona, Tucson, Arizona 85724, USA
    Clin Cancer Res 9:4961-71. 2003
    ..Therefore, we investigated a ligand-independent approach to hormonal therapy that depletes cellular levels of the receptor by inhibiting the function of Hsp90...
  32. ncbi request reprint Two cases of pediatric neuroblastoma with tumor thrombus in the inferior vena cava
    Rochelle Bagatell
    Department of Pediatrics and Steele Memorial Children s Research Center, Tucson, Arizona, USA
    J Pediatr Hematol Oncol 24:397-400. 2002
    ..In one patient a pulmonary embolus developed after initiation of cytotoxic therapy; the second patient was prophylactically anticoagulated and had no embolic event...
  33. ncbi request reprint A phase I study of 17-allylaminogeldanamycin in relapsed/refractory pediatric patients with solid tumors: a Children's Oncology Group study
    Brenda J Weigel
    University of Minnesota Cancer Center and Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Clin Cancer Res 13:1789-93. 2007
    ..To determine the recommended phase 2 dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the heat shock protein (Hsp) 90 inhibitor, 17-allylaminogeldanamycin (17-AAG)...
  34. ncbi request reprint Design of quinolinedione-based geldanamycin analogues
    Robert Hargreaves
    Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 1604, USA
    Bioorg Med Chem Lett 13:3075-8. 2003
    ..COMPARE analysis revealed that the LC(50) profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient)...
  35. ncbi request reprint Hsp90: an emerging target for breast cancer therapy
    Jason Beliakoff
    Department of Urology, Stanford University School of Medicine, CA, USA
    Anticancer Drugs 15:651-62. 2004
    ..Given the redundancy and complexity of the molecular abnormalities present in most breast cancers, the ability of Hsp90 inhibitors to alter the activity of multiple oncogenic targets may prove of unique therapeutic benefit...