K W Kohn

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc A formal MIM specification and tools for the common exchange of MIM diagrams: an XML-Based format, an API, and a validation method
    Augustin Luna
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    BMC Bioinformatics 12:167. 2011
  2. ncbi request reprint Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Ann N Y Acad Sci 922:11-26. 2000
  3. pmc Chromatin challenges during DNA replication: a systems representation
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 19:1-7. 2008
  4. pmc Depicting combinatorial complexity with the molecular interaction map notation
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
    Mol Syst Biol 2:51. 2006
  5. pmc Molecular interaction map of the mammalian cell cycle control and DNA repair systems
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Biol Cell 10:2703-34. 1999
  6. pmc Molecular interaction maps of bioregulatory networks: a general rubric for systems biology
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 17:1-13. 2006
  7. ncbi request reprint Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Biochem Biophys Res Commun 331:816-27. 2005
  8. ncbi request reprint Beyond DNA cross-linking: history and prospects of DNA-targeted cancer treatment--fifteenth Bruce F. Cain Memorial Award Lecture
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Res 56:5533-46. 1996
  9. ncbi request reprint An information-intensive approach to the molecular pharmacology of cancer
    J N Weinstein
    Laboratory of Molecular Pharmacology LMP, Division of Basic Science, National Cancer Institute NCI, National Institutes of Health, Bethesda, MD 20892, USA
    Science 275:343-9. 1997
  10. ncbi request reprint p21CDKN1A allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine
    T Furuta
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Oncogene 25:2839-49. 2006

Detail Information

Publications44

  1. pmc A formal MIM specification and tools for the common exchange of MIM diagrams: an XML-Based format, an API, and a validation method
    Augustin Luna
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    BMC Bioinformatics 12:167. 2011
    ..A lack of software tools for the notation restricts wider usage of the notation. Development of software is facilitated by a more detailed specification regarding software requirements than has previously existed for the MIM notation...
  2. ncbi request reprint Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Ann N Y Acad Sci 922:11-26. 2000
    ..This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy...
  3. pmc Chromatin challenges during DNA replication: a systems representation
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 19:1-7. 2008
    ..on the complexities of chromatin replication, thereby providing a tool for system-level comprehension of the effects of genetic mutations, altered gene expression, and pharmacologic intervention...
  4. pmc Depicting combinatorial complexity with the molecular interaction map notation
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
    Mol Syst Biol 2:51. 2006
    ..These comparisons may help cell and systems biologists adopt a graphical language that is unambiguous and generally understood...
  5. pmc Molecular interaction map of the mammalian cell cycle control and DNA repair systems
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Biol Cell 10:2703-34. 1999
    ..The map shows how multiprotein complexes could assemble and function at gene promoter sites and at sites of DNA damage. It also portrays the richness of connections between the p53-Mdm2 subsystem and other parts of the network...
  6. pmc Molecular interaction maps of bioregulatory networks: a general rubric for systems biology
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 17:1-13. 2006
    ..Drawing a MIM diagram, adhering to the rules of notation, imposes a logical discipline that sharpens one's understanding of the structure and function of a network...
  7. ncbi request reprint Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Biochem Biophys Res Commun 331:816-27. 2005
    ..We also used molecular interaction maps to propose a p53 Off-On switch in response to DNA damage...
  8. ncbi request reprint Beyond DNA cross-linking: history and prospects of DNA-targeted cancer treatment--fifteenth Bruce F. Cain Memorial Award Lecture
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Res 56:5533-46. 1996
    ..Panels of human tumor cell lines may serve to link the molecular defects with specific drug sensitivities. Such correlations could guide the selection of drugs for therapy based on molecular diagnosis of individual tumors...
  9. ncbi request reprint An information-intensive approach to the molecular pharmacology of cancer
    J N Weinstein
    Laboratory of Molecular Pharmacology LMP, Division of Basic Science, National Cancer Institute NCI, National Institutes of Health, Bethesda, MD 20892, USA
    Science 275:343-9. 1997
    ..It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents...
  10. ncbi request reprint p21CDKN1A allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine
    T Furuta
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Oncogene 25:2839-49. 2006
    ..However, these breaks are not related to apoptotic DNA fragmentation. We propose that p21(CDKN1A) prevents the collapse of replication forks damaged by stabilized topoisomerase I cleavage complexes...
  11. pmc Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes
    R G Shao
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    EMBO J 18:1397-406. 1999
    ..Keywords: camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation..
  12. pmc Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks
    Olivier Sordet
    Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892 4255, USA
    EMBO Rep 10:887-93. 2009
    ..Thus, we propose that Top1cc produce transcription arrests with R-loop formation and generate DSBs that activate ATM in post-mitotic cells...
  13. pmc Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways
    Stéphanie Solier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Mol Cell Biol 29:68-82. 2009
    ..Together, our findings suggest that nuclear activation of Chk2 by TRAIL acts as a positive feedback loop involving the mitochondrion-dependent activation of caspases, independently of p53...
  14. ncbi request reprint Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition
    K W Kohn
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Oncogene 16:1065-75. 1998
    ..The results show how network simulations, carried out by means of the methods described, can assist in the design and interpretation of experiments probing the control of the G1/S phase transition...
  15. ncbi request reprint Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents
    P M O'Connor
    Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 57:4285-300. 1997
    ..This information also allows for the large-scale analysis of the more than 60,000 compounds tested against these lines for novel agents that might exploit defective p53 function as a means of preferential toxicity...
  16. ncbi request reprint Quantitative structure-antitumor activity relationships of camptothecin analogues: cluster analysis and genetic algorithm-based studies
    Y Fan
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Med Chem 44:3254-63. 2001
    ..The cross-validated r(2) for the final GFA model was 0.783, indicating a predictive QSAR model...
  17. ncbi request reprint Transcriptional regulation of mitotic genes by camptothecin-induced DNA damage: microarray analysis of dose- and time-dependent effects
    Yi Zhou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 62:1688-95. 2002
    ....
  18. ncbi request reprint G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently
    P M O'Connor
    Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 268:8298-308. 1993
    ..Furthermore, we found that pentoxifylline disrupts the signal transduction pathway that regulates these complexes when damaged DNA is present, resulting in abrogation of cell cycle arrest...
  19. ncbi request reprint UCN-01 inhibits p53 up-regulation and abrogates gamma-radiation-induced G(2)-M checkpoint independently of p53 by targeting both of the checkpoint kinases, Chk2 and Chk1
    Qiang Yu
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4255, USA
    Cancer Res 62:5743-8. 2002
    ..Taken together, these observations indicate that UCN-01 can modulate both Chk1 and Chk2 in intact cells and enhance IR-induced apoptosis in p53-deficient, and consequently p21-deficient, cells...
  20. ncbi request reprint Dose-response transition from cell cycle arrest to apoptosis with selective degradation of Mdm2 and p21WAF1/CIP1 in response to the novel anticancer agent, aminoflavone (NSC 686,288)
    L H Meng
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Oncogene 26:4806-16. 2007
    ....
  21. pmc Genome-wide analysis of novel splice variants induced by topoisomerase I poisoning shows preferential occurrence in genes encoding splicing factors
    Stéphanie Solier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 4255, USA
    Cancer Res 70:8055-65. 2010
    ..The preferential effect of CPT on genes encoding splicing factors may explain the abnormal splicing of a large number of genes in response to Top1cc...
  22. ncbi request reprint Comparative pharmacokinetics of DNA lesion formation and removal following treatment of L1210 cells with nitrogen mustards
    P M O'Connor
    Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Cancer Commun 2:387-94. 1990
    ..QM was the only compound that produced detectable SSB, and the SSB were so numerous that ISC could not be quantitated.(ABSTRACT TRUNCATED AT 250 WORDS)..
  23. ncbi request reprint DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata
    Y Pommier
    Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Biochemistry 35:13303-9. 1996
    ..These data indicate that ecteinascidin 743 is a novel DNA minor groove, guanine-specific alkylating agent...
  24. ncbi request reprint Network architecture of signaling from uncoupled helicase-polymerase to cell cycle checkpoints and trans-lesion DNA synthesis
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Cell Cycle 8:2281-99. 2009
    ..In addition, the network architecture disclosed by the hierarchical map, suggested a speculative model for how molecular crowding and the granular localization of network components in the cell nucleus can facilitate function...
  25. ncbi request reprint Chk2 molecular interaction map and rationale for Chk2 inhibitors
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4255, USA
    Clin Cancer Res 12:2657-61. 2006
    ..Visualizing the regulatory circuits underlying cellular signaling may help identify key regulatory reactions and defects that can serve as targets for anticancer drugs...
  26. ncbi request reprint Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma
    Joseph Riss
    Laboratory of Biosystems and Cancer, Comparative Oncology Program, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 66:7216-24. 2006
    ..The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia...
  27. pmc mRNA and microRNA expression profiles of the NCI-60 integrated with drug activities
    Hongfang Liu
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Mol Cancer Ther 9:1080-91. 2010
    ..The data sets presented here will facilitate the identification of groups of mRNAs, microRNAs, and drugs that potentially affect and interact with one another...
  28. pmc A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex
    Christophe Marchand
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Building 37, Room 5068, Bethesda, MD 20892 4255, USA
    Mol Cancer Ther 5:287-95. 2006
    ..Stabilization of such conformational states results in uncompetitive inhibition and exemplifies the relevance of screening for ligands and drugs that stabilize ("trap") these macromolecular complexes...
  29. ncbi request reprint Targeting chk2 kinase: molecular interaction maps and therapeutic rationale
    Yves Pommier
    Center for Cancer Research, National Cancer Institute, National Institute of Health, DHHS, Bethesda, Maryland, USA
    Curr Pharm Des 11:2855-72. 2005
    ..Chk2 inhibitors might be used to enhance the tumor selectivity of DNA targeted agents in p53-deficient tumors, and for the treatment of tumors whose growth depends on enhanced Chk2 activity...
  30. ncbi request reprint Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling, functional analysis, and molecular interaction mapping
    William C Reinhold
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cancer Res 63:1000-11. 2003
    ..This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis...
  31. ncbi request reprint [Cell cycle and checkpoints in oncology: new therapeutic targets]
    Yves Pommier
    Laboratoire de Pharmacologie Moleculaire, Center for Cancer Research, National Cancer Institute, Bldg 37, Room 5068, NIH, Bethesda, MD 20892 4255, USA
    Med Sci (Paris) 19:173-86. 2003
    ..This review is an update of the molecular networks driving the cell cycle and its regulation, and of the importance of this knowledge for understanding the mechanisms driving oncogenesis and therapeutic developments...
  32. ncbi request reprint Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, MD 20892, USA
    Oncogene 23:2934-49. 2004
    ..They complement the p53, Chk2 and c-Abl maps published recently. We will also introduce the 'permissive apoptosis-resistance' model for the selection of multidrug-resistant cells...
  33. ncbi request reprint Molecular interaction maps--a diagrammatic graphical language for bioregulatory networks
    Mirit I Aladjem
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Sci STKE 2004:pe8. 2004
    ....
  34. ncbi request reprint Repair of and checkpoint response to topoisomerase I-mediated DNA damage
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute NIH, Building 37, Room 5068, Bethesda, MD 20892 4255, USA
    Mutat Res 532:173-203. 2003
    ..Defects in these repair/checkpoint pathways, which promote tumor development, explain, at least in part, the selectivity of camptothecins and other Top1 inhibitors for cancer cells...
  35. ncbi request reprint Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes
    Ze Hong Miao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    DNA Repair (Amst) 5:1489-94. 2006
    ....
  36. ncbi request reprint Differential induction of topoisomerase I-DNA cleavage complexes by the indenoisoquinoline MJ-III-65 (NSC 706744) and camptothecin: base sequence analysis and activity against camptothecin-resistant topoisomerases I
    Smitha Antony
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Bethesda, MD 20892 4255, USA
    Cancer Res 63:7428-35. 2003
    ..This study shows the specific molecular interactions of MJ-III-65 with top1 and demonstrates that MJ-III-65 is a potentially useful top1 inhibitor that enhances and traps top1 cleavage sites not sensitive to CPTs...
  37. ncbi request reprint 4-nitroquinoline-1-oxide induces the formation of cellular topoisomerase I-DNA cleavage complexes
    Ze Hong Miao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Cancer Res 66:6540-5. 2006
    ..Induction of Top1cc and histone gamma-H2AX by 4NQO may contribute to the cellular effects of 4NQO, including its selective activity toward RecQ helicase BLM-deficient cells...
  38. pmc Properties of switch-like bioregulatory networks studied by simulation of the hypoxia response control system
    Kurt W Kohn
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Biol Cell 15:3042-52. 2004
    ..The studies disclosed the mechanism responsible for the sharp transitions. We show how parameter sets giving switch-like behavior can be found and how this type of behavior provides a foundation for quantitative studies in cells...
  39. ncbi request reprint Apoptosis induced by topoisomerase inhibitors
    Olivier Sordet
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4255, USA
    Curr Med Chem Anticancer Agents 3:271-90. 2003
    ..Finally, we will review the recent observations that support a role for topoisomerases in chromatin fragmentation during the execution phase of apoptosis...
  40. pmc The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth
    Q Zhan
    Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892
    Mol Cell Biol 14:2361-71. 1994
    ..Taken together, these observations indicate that these genes define a novel class of mammalian genes encoding acidic proteins involved in the control of cellular growth...
  41. pmc Predicted functions of MdmX in fine-tuning the response of p53 to DNA damage
    Sohyoung Kim
    Laboratory of Molecular Pharmacology, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
    PLoS Comput Biol 6:e1000665. 2010
    ..Our study suggests how MdmX may participate in the response of p53 to DNA damage either by increasing dependency of p53 on Mdm2 or by dampening oscillations of p53 activity and presents a model for experimental investigation...
  42. ncbi request reprint Impact of p53 knockout and topotecan treatment on gene expression profiles in human colon carcinoma cells: a pharmacogenomic study
    Sayed S Daoud
    Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164, USA
    Cancer Res 63:2782-93. 2003
    ..The new experimental design and gene expression map analysis introduced here are applicable to a wide range of studies that encompass both treatment effects and genotypic or phenotypic differences...
  43. pmc Circuit diagrams for biological networks
    Kurt W Kohn
    Mol Syst Biol 2:2006.0002. 2006
  44. pmc Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone action
    Dirk Strumberg
    Department of Internal Medicine and Medical Oncology, West German Cancer Center, University Medical School of Essen, 45122 Essen, Germany
    Antimicrob Agents Chemother 46:2735-46. 2002
    ..It also demonstrates that selective amino acid residues in the alpha4-helix are important in determining the activity and possibly the binding of quinolones to the topoisomerase II-DNA complexes...