MICHAEL BARRY KASTAN

Summary

Affiliation: St. Jude Children's Research Hospital
Country: USA

Publications

  1. ncbi The many substrates and functions of ATM
    M B Kastan
    Department of Hematology Oncology, Saint Jude Children s Research Hospital, D1034, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 1:179-86. 2000
  2. ncbi ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
    Jochen G Schneider
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell Metab 4:377-89. 2006
  3. ncbi p53: a two-faced cancer gene
    Michael B Kastan
    Nat Cell Biol 9:489-91. 2007
  4. pmc Our cells get stressed too! Implications for human disease
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Blood Cells Mol Dis 39:148-50. 2007
  5. ncbi Cell-cycle checkpoints and cancer
    Michael B Kastan
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 432:316-23. 2004
  6. doi DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cancer Res 6:517-24. 2008
  7. ncbi Wild-type p53: tumors can't stand it
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell 128:837-40. 2007
  8. ncbi ATM--a key determinant of multiple cellular responses to irradiation
    M B Kastan
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Acta Oncol 40:686-8. 2001
  9. pmc Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis
    Kirsteen H Maclean
    Division of Molecular Therapeutics, Department of Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Clin Invest 118:79-88. 2008
  10. ncbi Atm deficiency affects both apoptosis and proliferation to augment Myc-induced lymphomagenesis
    Kirsteen H Maclean
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Mol Cancer Res 5:705-11. 2007

Research Grants

  1. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL KASTAN; Fiscal Year: 2007
  2. LABORATORY TRAINING FOR CLINICAL ONCOLOGISTS
    MICHAEL KASTAN; Fiscal Year: 2007
  3. Cellular Stress Response Signaling Pathways
    MICHAEL KASTAN; Fiscal Year: 2007
  4. St.Jude Children's Cancer Center Support Grant (CCSG)
    MICHAEL KASTAN; Fiscal Year: 2007
  5. FUNCTIONAL CHARACTERIZATION OF THE ATM GENE PRODUCT
    MICHAEL KASTAN; Fiscal Year: 2009
  6. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL KASTAN; Fiscal Year: 2005
  7. ATM GENE AND CELLULAR RESPONSES TO IRRADIATION
    MICHAEL KASTAN; Fiscal Year: 1999
  8. P53 AND THE CELLULAR RESPONSE TO DNA DAMAGE
    MICHAEL KASTAN; Fiscal Year: 2001
  9. MOLECULAR MECHANISMS OF MAMMALIAN CHECKPOINT PATHWAYS
    MICHAEL KASTAN; Fiscal Year: 2004
  10. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL BARRY KASTAN; Fiscal Year: 2010

Collaborators

Detail Information

Publications44

  1. ncbi The many substrates and functions of ATM
    M B Kastan
    Department of Hematology Oncology, Saint Jude Children s Research Hospital, D1034, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 1:179-86. 2000
    ..Although it is hard to understand how a single gene product is involved in so many physiological processes, a clear picture is starting to emerge...
  2. ncbi ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
    Jochen G Schneider
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell Metab 4:377-89. 2006
    ..These results suggest that ATM-dependent stress pathways mediate susceptibility to the metabolic syndrome and that chloroquine or related agents promoting ATM activity could modulate insulin resistance and decrease vascular disease...
  3. ncbi p53: a two-faced cancer gene
    Michael B Kastan
    Nat Cell Biol 9:489-91. 2007
  4. pmc Our cells get stressed too! Implications for human disease
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Blood Cells Mol Dis 39:148-50. 2007
    ..Conversely, activators of ATM could improve responses to cellular stresses such as oxidative damage. The potential benefits of ATM modulation in disease settings ranging from metabolic syndrome to cancer will be discussed...
  5. ncbi Cell-cycle checkpoints and cancer
    Michael B Kastan
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 432:316-23. 2004
    ..These cellular responses are also important for determining toxicities and responses to current cancer therapies, most of which target the DNA...
  6. doi DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cancer Res 6:517-24. 2008
    ..Relevant to the latter, we have shown benefits of an ATM activator in disease settings ranging from metabolic syndrome to cancer prevention...
  7. ncbi Wild-type p53: tumors can't stand it
    Michael B Kastan
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell 128:837-40. 2007
    ..Martins et al. (2006) also demonstrate that restoration of p53 activity results in tumor regression but add the sobering caveat that tumors may be able to quickly generate resistance by finding other ways to disrupt the p53 pathway...
  8. ncbi ATM--a key determinant of multiple cellular responses to irradiation
    M B Kastan
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Acta Oncol 40:686-8. 2001
    ..Such insights also result in the identification of potential new targets for enhancing the efficacy of radiation therapy...
  9. pmc Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis
    Kirsteen H Maclean
    Division of Molecular Therapeutics, Department of Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Clin Invest 118:79-88. 2008
    ....
  10. ncbi Atm deficiency affects both apoptosis and proliferation to augment Myc-induced lymphomagenesis
    Kirsteen H Maclean
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Mol Cancer Res 5:705-11. 2007
    ..Therefore, regulation of cell proliferation and p27(Kip1) seems to be a contributing mechanism by which Atm holds tumor formation in check...
  11. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
    ....
  12. pmc Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage
    Seong Tae Kim
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennesee 38105 2794, USA
    Genes Dev 16:560-70. 2002
    ..These results demonstrate that Smc1 participates in cellular responses to DNA damage and link Smc1 to the Atm signal transduction pathway...
  13. pmc Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation
    Michael D Rainey
    Department of Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 68:7466-74. 2008
    ..The ability of CP466722 to rapidly and reversibly regulate ATM activity provides a new tool to ask questions about ATM function that could not easily be addressed using genetic models or RNA interference technologies...
  14. ncbi Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair
    Elijahu Berkovich
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Nat Cell Biol 9:683-90. 2007
    ....
  15. pmc Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway
    Risa Kitagawa
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38018, USA
    Genes Dev 18:1423-38. 2004
    ..These observations suggest that many of the abnormal stress responses seen in cells lacking ATM, NBS1, or BRCA1 result from a failure of ATM migration to sites of DNA breaks and a resultant lack of SMC1 phosphorylation...
  16. ncbi Disappearance of the telomere dysfunction-induced stress response in fully senescent cells
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 64:3748-52. 2004
    ....
  17. ncbi A subtle t(3;8) results in plausible juxtaposition of MYC and BCL6 in a child with Burkitt lymphoma/leukemia and ataxia-telangiectasia
    John T Sandlund
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Cancer Genet Cytogenet 168:69-72. 2006
    ..1) that rearranged BCL6 and placed it adjacent to MYC. We speculate that this genetic lesion occurred as a result of chromosomal instability due to the underlying disease...
  18. pmc Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia
    Wing Leung
    Department of Oncology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 2794, USA
    Cancer Epidemiol 34:303-8. 2010
    ..Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage...
  19. ncbi Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation
    Bo Xu
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 62:4588-91. 2002
    ..This demonstrates that loss of this checkpoint function by itself does not affect cell survival and suggests that some other function of Brca1 alters cell survival after DNA damage...
  20. pmc Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation
    Bo Xu
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 22:1049-59. 2002
    ..Thus, two different G(2) arrest mechanisms are present in mammalian cells, and the type of cell cycle checkpoint assay to be used in experimental investigation must be thoughtfully selected...
  21. pmc Multiple roles of ATM in monitoring and maintaining DNA integrity
    Frederick A Derheimer
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    FEBS Lett 584:3675-81. 2010
    ....
  22. ncbi Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin
    Masatoshi Takagi
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cell 123:49-63. 2005
    ..These findings demonstrate the importance of increased translation of p53 in DNA-damage responses and suggest critical roles for RPL26 and nucleolin in affecting p53 induction...
  23. ncbi Initiating cellular stress responses
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 N Lauderdale Street, Memphis, TN 38105, USA
    Cell 118:9-17. 2004
    ..Control mechanisms include the localization of PIKKs into multiprotein complexes at the sites of damage and mediation of protein-protein contacts such that substrates are allowed access to the PIKK catalytic domains...
  24. pmc The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis
    Md Hasan Zaki
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Immunity 32:379-91. 2010
    ..Thus, the Nlrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis...
  25. ncbi Phosphatases join kinases in DNA-damage response pathways
    Christopher J Bakkenist
    Department of Hematology and Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Trends Cell Biol 14:339-41. 2004
    ..Three recent articles describe roles for two phosphatases in signaling pathways that are activated after DNA damage...
  26. pmc 5'-3'-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage
    Jing Chen
    Department of Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 24:2146-56. 2010
    ..The ability to reduce stress induction of p53 with oligonucleotides or other small molecules has numerous potential therapeutic uses...
  27. pmc NAD+ modulates p53 DNA binding specificity and function
    Kevin G McLure
    Department of Hematology Oncology, St Jude Children s Research Hospital, Room D 5048, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Mol Cell Biol 24:9958-67. 2004
    ..Thus, niacinamide and thiamine form a novel basis for the development of small molecules that affect p53 function in vivo, and these results suggest that changes in cellular energy metabolism may regulate p53...
  28. pmc Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response
    Chandtip Chandhasin
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    J Virol 82:6952-61. 2008
    ..Attempts to replicate in the presence of these lesions would result in gradual accumulation of mutations, leading to genome instability and cellular transformation...
  29. ncbi Ataxia telangiectasia-mutated and p53 are potential mediators of chloroquine-induced resistance to mammary carcinogenesis
    Christian R Loehberg
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cancer Res 67:12026-33. 2007
    ..Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis...
  30. pmc A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage
    Xi Tang
    Department of Biochemistry and Molecular Biology, Southern Research Institute, 2000 9th Ave South, Birmingham, AL 35205, USA
    Mol Cell Biol 28:2559-66. 2008
    ..Collectively, the results of these studies demonstrate a novel pathway that links ATM, PP1, and I-2 in the cellular response to DNA damage...
  31. ncbi Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation
    Renu Garg
    Department of Genetics and Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, Room 406, CSRB Building, 533 Bolivar Street, New Orleans, LA 70112, USA
    Mol Cancer Res 2:362-9. 2004
    ..These results suggest that low-dose UV radiation activates an S-phase checkpoint requiring ATR-mediated signal transduction pathway...
  32. ncbi Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage
    Joo Hyeon Lee
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
    Mol Cancer Res 1:674-81. 2003
    ..Together, these data demonstrate that multiple functional domains of NBS1 are required for ATM-dependent activation of CHK2, nuclear focus formation, S phase checkpoint control, and cell survival after exposure to IR...
  33. ncbi Interaction of FANCD2 and NBS1 in the DNA damage response
    Koji Nakanishi
    Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Nat Cell Biol 4:913-20. 2002
    ..NBS1 and FANCD2 therefore cooperate in two distinct cellular functions, one involved in the DNA crosslink response and one involved in the S-phase checkpoint response...
  34. ncbi Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways
    Toshiyasu Taniguchi
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Department of Pediatrics, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 109:459-72. 2002
    ..Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity...
  35. pmc The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response
    Jan Karlseder
    Laboratory for Cell Biology and Genetics, Rockefeller University, New York, USA
    PLoS Biol 2:E240. 2004
    ....
  36. ncbi ATM activation in normal human tissues and testicular cancer
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark
    Cell Cycle 4:838-45. 2005
    ..The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies...
  37. ncbi Cell biology: A BID for the pathway
    Michael B Kastan
    Nature 437:1103. 2005
  38. pmc The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor
    Monica Morales
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    Genes Dev 19:3043-54. 2005
    ....
  39. pmc Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
    Simon Bekker-Jensen
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    J Cell Biol 173:195-206. 2006
    ..We propose that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance...
  40. ncbi Distinct functional domains of Nbs1 modulate the timing and magnitude of ATM activation after low doses of ionizing radiation
    Zuzana Horejsi
    Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, Copenhagen DK 2100 Denmark
    Oncogene 23:3122-7. 2004
    ..Although not absolutely required for ATM activation, the MRN nuclease complex may help reach the threshold activity of ATM necessary for optimal genome maintenance and prevention of cancer...
  41. pmc Molecular cross-talk among chromosome fragility syndromes
    Jordi Surralles
    Group of Mutagenesis, Department of Genetics and Microbiology, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
    Genes Dev 18:1359-70. 2004
  42. ncbi Analyzing cell cycle checkpoints after ionizing radiation
    Bo Xu
    Department of Genetics and Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, USA
    Methods Mol Biol 281:283-92. 2004
    ....
  43. pmc BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function
    Martin F Arlt
    Department of Human Genetics, 4909 Buhl, Box 0618, 1241 E Catherine Street, University of Michigan, Ann Arbor, MI 48109 0618, USA
    Mol Cell Biol 24:6701-9. 2004
    ..Furthermore, they suggest that mutations in BRCA1 or interacting proteins could lead to rearrangements at fragile sites in cancer cells...
  44. doi Assessment of protein dynamics and DNA repair following generation of DNA double-strand breaks at defined genomic sites
    Elijahu Berkovich
    Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Protoc 3:915-22. 2008
    ..Starting with fragmented chromatin, results can be achieved in 2-3 d...

Research Grants35

  1. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL KASTAN; Fiscal Year: 2007
    ..These studies will help us understand how cells respond to DNA damage and other stresses at the molecular level. ..
  2. LABORATORY TRAINING FOR CLINICAL ONCOLOGISTS
    MICHAEL KASTAN; Fiscal Year: 2007
    ..This manpower concern is particularly acute in Pediatric subspecialties. Graduates of the training program supported by this application will fill this critical need. ..
  3. Cellular Stress Response Signaling Pathways
    MICHAEL KASTAN; Fiscal Year: 2007
    ..In tow, these studies should provide significant new information that has implications for both tumor development and therapy. ..
  4. St.Jude Children's Cancer Center Support Grant (CCSG)
    MICHAEL KASTAN; Fiscal Year: 2007
    ..St. Jude Children's Research Hospital recently went through a vigorous Strategic Planning process and made a strong and long-term commitment to remain focused on cancer research. ..
  5. FUNCTIONAL CHARACTERIZATION OF THE ATM GENE PRODUCT
    MICHAEL KASTAN; Fiscal Year: 2009
    ..Experiments are proposed to further explore the molecular mechanisms involved in both the radioprotective effects and the cancer preventative effects of ATM activation. ..
  6. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL KASTAN; Fiscal Year: 2005
    ..Significant insights into the role of SMC1 phosphorylation can be gained by studies of the organ development and responses to irradiation as well as from generation of cell lines from these mice. ..
  7. ATM GENE AND CELLULAR RESPONSES TO IRRADIATION
    MICHAEL KASTAN; Fiscal Year: 1999
    ..These studies also have therapeutic implications since inhibition of ATM function should cause increased tumor cell death in response to a number of anti-neoplastic therapies. ..
  8. P53 AND THE CELLULAR RESPONSE TO DNA DAMAGE
    MICHAEL KASTAN; Fiscal Year: 2001
    ..4) A neuroblastoma model system in which irradiation-induced differentiation is dependent on p53 will be used to clarify the roles of Gadd45, N-myc, Mad-3 and cdc25 in this process. ..
  9. MOLECULAR MECHANISMS OF MAMMALIAN CHECKPOINT PATHWAYS
    MICHAEL KASTAN; Fiscal Year: 2004
    ....
  10. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL BARRY KASTAN; Fiscal Year: 2010
    ..These studies will help us understand how cells respond to DNA damage and other stresses at the molecular level. ..