CHARLES SCOTT CRAIK

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides
    Carlos E Cruz
    Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508 900, Brazil
    Parasit Vectors 3:63. 2010
  2. pmc GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data
    Marie E Fahey
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158, USA
    BMC Bioinformatics 12:298. 2011
  3. doi request reprint Proteases as therapeutics
    Charles S Craik
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94131, USA
    Biochem J 435:1-16. 2011
  4. ncbi request reprint Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries
    Mary A Mathieu
    Department of Pathology, UCSF, San Francisco, CA 94143, USA
    Mol Biochem Parasitol 121:99-105. 2002
  5. pmc Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer
    Aaron M LeBeau
    Department of Pharmacology and Molecular Science, The Johns Hopkins University School of Medicine, Baltimore, MD 2131, USA
    Biol Chem 391:333-43. 2010
  6. pmc Positional scanning synthetic combinatorial libraries for substrate profiling
    Eric L Schneider
    Department of Pharmaceutical Chemistry, The University of California, San Francisco, San Francisco, CA, USA
    Methods Mol Biol 539:59-78. 2009
  7. pmc Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3
    Shoba Subramanian
    Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 4:e5156. 2009
  8. ncbi request reprint Scanning the prime-site substrate specificity of proteolytic enzymes: a novel assay based on ligand-enhanced lanthanide ion fluorescence
    Amy M Barrios
    Department of Pharmaceutical Chemistry, University of California, San Francisco 94143, USA
    Bioorg Med Chem Lett 12:3619-23. 2002
  9. pmc Identification of the major cysteine protease of Giardia and its role in encystation
    Kelly N DuBois
    Department of Pathology, the Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, CA 94158, USA
    J Biol Chem 283:18024-31. 2008
  10. pmc Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites
    Ajay Singh
    Department of Medicine, San Francisco General Hospital, San Francisco, CA 94143, USA
    Biochem J 368:273-81. 2002

Collaborators

Detail Information

Publications50

  1. pmc Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides
    Carlos E Cruz
    Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508 900, Brazil
    Parasit Vectors 3:63. 2010
    ..abstract:..
  2. pmc GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data
    Marie E Fahey
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158, USA
    BMC Bioinformatics 12:298. 2011
    ..Because these host-pathogen interactions are extensive and interactions between human proteins are found within many different databases, it is difficult to generate integrated HIV-human interaction networks...
  3. doi request reprint Proteases as therapeutics
    Charles S Craik
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94131, USA
    Biochem J 435:1-16. 2011
    ..Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications...
  4. ncbi request reprint Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries
    Mary A Mathieu
    Department of Pathology, UCSF, San Francisco, CA 94143, USA
    Mol Biochem Parasitol 121:99-105. 2002
    ..Predictions of substrate specificity from the library screen were confirmed using single peptide substrates for kinetic assays...
  5. pmc Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer
    Aaron M LeBeau
    Department of Pharmacology and Molecular Science, The Johns Hopkins University School of Medicine, Baltimore, MD 2131, USA
    Biol Chem 391:333-43. 2010
    ..In addition, the unique active site characteristics of PSA and how these motifs aided our research in developing PSA targeted agents are highlighted...
  6. pmc Positional scanning synthetic combinatorial libraries for substrate profiling
    Eric L Schneider
    Department of Pharmaceutical Chemistry, The University of California, San Francisco, San Francisco, CA, USA
    Methods Mol Biol 539:59-78. 2009
    ..These sequences can be readily verified through kinetic measurements on single peptide substrates and utilized to further knowledge of the role of proteases in cancer...
  7. pmc Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3
    Shoba Subramanian
    Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 4:e5156. 2009
    ..falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents...
  8. ncbi request reprint Scanning the prime-site substrate specificity of proteolytic enzymes: a novel assay based on ligand-enhanced lanthanide ion fluorescence
    Amy M Barrios
    Department of Pharmaceutical Chemistry, University of California, San Francisco 94143, USA
    Bioorg Med Chem Lett 12:3619-23. 2002
    ..Furthermore, the continuous fluorogenic assay described may prove useful in analyzing the activity of other hydrolytic enzymes...
  9. pmc Identification of the major cysteine protease of Giardia and its role in encystation
    Kelly N DuBois
    Department of Pathology, the Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, CA 94158, USA
    J Biol Chem 283:18024-31. 2008
    ..These data suggest that Giardia cysteine protease 2 is not only the major cysteine endoprotease expressed in Giardia, but is also central to the encystation process...
  10. pmc Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites
    Ajay Singh
    Department of Medicine, San Francisco General Hospital, San Francisco, CA 94143, USA
    Biochem J 368:273-81. 2002
    ..It indicates that drug discovery studies must take into account important differences between plasmodial proteases and sheds light on the critical role of amino acid 23 in catalysis by papain-family proteases...
  11. ncbi request reprint Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities
    Youngchool Choe
    Department of Pharmaceutical Chemistry, University of California at San Francisco, California 94143, USA
    J Biol Chem 281:12824-32. 2006
    ..This approach provides useful information for developing selective chemical probes to study protease-related pathologies and physiologies...
  12. pmc Using specificity to strategically target proteases
    Mark D Lim
    Department of Pharmaceutical Chemistry, University of California, School of Pharmacy, 513 Parnassus Avenue Room S 926, San Francisco, CA 94158, USA
    Bioorg Med Chem 17:1094-100. 2009
    ..The use of these approaches to better understand a protease's natural substrate will be discussed as well as the technologies that emerged...
  13. ncbi request reprint Characterization of structural determinants of granzyme B reveals potent mediators of extended substrate specificity
    Sandra Waugh Ruggles
    Graduate Group in Biophysics, University of California, San Francisco, California 94143 2280, USA
    J Biol Chem 279:30751-9. 2004
    ..This study confirms four determinants of granzyme B extended substrate specificity that constitute a canon applicable to the study of the remaining family members...
  14. ncbi request reprint Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme B
    Sami Mahrus
    Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, California 94143 2280, USA
    J Biol Chem 279:54275-82. 2004
    ..Proteinase inhibitor 9 was effectively hydrolyzed and inactivated by human granzyme M, raising the possibility that this orphan granzyme bypasses proteinase inhibitor 9 inhibition of granzyme B...
  15. pmc Herpesvirus protease inhibition by dimer disruption
    Nobuhisa Shimba
    Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th St, Box 2280, San Francisco, CA 94143 2280, USA
    J Virol 78:6657-65. 2004
    ..These results indicate that the dimer interface, as well as the active sites, of herpesvirus proteases is a viable target for inhibiting enzyme activity...
  16. pmc SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 3:e449. 2009
    ..Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins...
  17. pmc Vinyl sulfones as antiparasitic agents and a structural basis for drug design
    Iain D Kerr
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 284:25697-703. 2009
    ....
  18. ncbi request reprint Development of alpha-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease
    Youngchool Choe
    Department of Pharmaceutical Chemistry, 600 16th Street, University of California at San Francisco, San Francisco, CA 94143 2280, USA
    Bioorg Med Chem 13:2141-56. 2005
    ..This study also demonstrates the validity of structure-guided approaches to focused library design and lead compound optimization...
  19. ncbi request reprint Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site
    Wilfred W Raymond
    Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0911, USA
    J Biol Chem 278:34517-24. 2003
    ..8 nM) and 2,700- and 1,300-fold selective for chymase over cathepsin G and chymotrypsin, respectively. In summary, these findings reveal albumin to be a substrate for chymase and identify a potentially useful new chymase inhibitor...
  20. ncbi request reprint Potent and selective inhibition of membrane-type serine protease 1 by human single-chain antibodies
    Jeonghoon Sun
    Department of Pharmaceutical Chemistry, University of California, San Francisco, 513 Parnassus, San Francisco, California 94143, USA
    Biochemistry 42:892-900. 2003
    ..These antibodies constitute a new class of highly selective protease inhibitors that can be used to dissect the biological roles of proteolytic enzymes as well as to develop diagnostic and therapeutic reagents...
  21. ncbi request reprint Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes
    Jason P Salter
    University of California San Francisco Graduate Program in Biomedical Sciences and the Department of Pathology, University of California, San Francisco, California 94143, USA
    J Biol Chem 277:24618-24. 2002
    ....
  22. pmc Identification and biochemical characterization of vivapains, cysteine proteases of the malaria parasite Plasmodium vivax
    Byoung Kuk Na
    Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143 0811, USA
    Biochem J 378:529-38. 2004
    ..Considering inhibitor profiles, the vivapains were inhibited by fluoromethylketone and vinyl sulphone inhibitors that also inhibited falcipains and have demonstrated potent antimalarial activity...
  23. pmc A parasite cysteine protease is key to host protein degradation and iron acquisition
    Theresa C O'Brien
    Department of Pathology and Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 283:28934-43. 2008
    ..Because even a modest deficiency in tbcatB is lethal for the parasite, tbcatB is a logical target for the development of new anti-trypanosomal chemotherapy...
  24. pmc Inhibition of a viral enzyme by a small-molecule dimer disruptor
    Tina Shahian
    Graduate Group in Biochemistry and Molecular Biology, University of California, San Francisco, California, USA
    Nat Chem Biol 5:640-6. 2009
    ..These results validate the interface of herpesvirus proteases and other similar oligomeric interactions as suitable targets for the development of small-molecule inhibitors...
  25. doi request reprint Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation
    A Allart Stoop
    Department of Pharmaceutical Chemistry, University of California San Francisco, 94143 2280, USA
    Biol Chem 391:425-33. 2010
    ..We used ecotin-Pkal to specifically inhibit contact activation of human plasma at the level mediated by plasma kallikrein...
  26. doi request reprint How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution
    Wilfred W Raymond
    Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA
    J Immunol 185:5360-8. 2010
    ....
  27. pmc Coordinate expression and functional profiling identify an extracellular proteolytic signaling pathway
    Ami S Bhatt
    Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 104:5771-6. 2007
    ..Individually, MT-SP1 and RON overexpression have been implicated in cancer progression and metastasis. Transcriptional coexpression of these genes suggests that this signaling pathway may be involved in several human cancers...
  28. ncbi request reprint Granzyme B proteolyzes receptors important to proliferation and survival, tipping the balance toward apoptosis
    Carly R K Loeb
    Department of Biochemistry and Biophysics, Tetrad Graduate Program, University of California, San Francisco, 94131, USA
    J Biol Chem 281:28326-35. 2006
    ..Therefore, granzyme B not only activates pro-death functions within a target, but also has a previously unidentified role in inactivating pro-growth signals to cause cell death...
  29. pmc Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease
    Deborah S Dauber
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, San Francisco, California 94143, USA
    J Virol 76:1359-68. 2002
    ..Understanding the altered substrate specificity of drug-resistant HIV PR should be valuable in the design of future generations of protease inhibitors as well as in elucidating the molecular basis of regulation of proteolysis in HIV...
  30. ncbi request reprint Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structure
    K Kinkead Reiling
    Department of Biochemistry and Biophysics, Graduate Group in Biophysics, University of California at San Francisco, San Francisco, California 94143, USA
    Biochemistry 41:4582-94. 2002
    ....
  31. ncbi request reprint The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity
    Jessica K Bell
    Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, USA
    Nat Struct Biol 10:527-34. 2003
    ..The crystal structure, along with substrate library profiling and mutagenesis, has allowed us to identify and rationally manipulate key components involved in GzmA substrate specificity...
  32. pmc The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase
    Christopher T Eggers
    Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143 92280, USA
    Biochem J 379:107-18. 2004
    ..This suggests that an important part of the antimicrobial mechanism of neutrophil elastase may be a periplasmic bacteriostatic effect of protease that has translocated across the damaged outer membrane...
  33. pmc Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor
    Alan B Marnett
    Program in Chemistry and Chemical Biology, Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 101:6870-5. 2004
    ....
  34. pmc Substrate modulation of enzyme activity in the herpesvirus protease family
    Ana Lazic
    Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158 2517, USA
    J Mol Biol 373:913-23. 2007
    ..This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme...
  35. ncbi request reprint Papa's got a brand new tag: advances in identification of proteases and their substrates
    Alan B Marnett
    Program in Chemistry and Chemical Biology, Department of Pharmaceutical Chemistry, The University of California, San Francisco, California 94143, USA
    Trends Biotechnol 23:59-64. 2005
    ..Here, we focus on several recently developed techniques representing crucial advances toward identification of proteases and their natural substrates...
  36. pmc Conversion of trypsin to a functional threonine protease
    Teaster T Baird
    University of California, San Francisco, Department of Pharmaceutical Chemistry, San Francisco, California 94143 2280, USA
    Protein Sci 15:1229-38. 2006
    ..Removal of the disulfide bridge decreases the overall thermostability of the enzyme, but it is partially rescued by the presence of threonine at position 195...
  37. ncbi request reprint Selective inhibition of the collagenolytic activity of human cathepsin K by altering its S2 subsite specificity
    Fabien Lecaille
    Department of Human Genetics, Mount Sinai School of Medicine, Box 1498, New York, New York 10029, USA
    Biochemistry 41:8447-54. 2002
    ..These results indicate that Tyr67 and Leu205 play a key role in the binding of proline residues in the S2 pocket of cathepsin K and are required for its unique collagenase activity...
  38. doi request reprint Characterization of a cysteine protease from Tritrichomonas foetus that induces host-cell apoptosis
    John J Lucas
    Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 4257 Weiskotten Hall, 766 Irving Avenue, Syracuse, NY 13210, USA
    Arch Biochem Biophys 477:239-43. 2008
    ..In addition, the DNA sequence was completed by 3' and 5' rapid amplification of cDNA ends (RACE) and the full-length amino acid sequence was obtained...
  39. ncbi request reprint Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore
    Dustin J Maly
    Department of Chemistry, University of California, Berkeley, California 94720, USA
    J Org Chem 67:910-5. 2002
    ..Finally, procedures are included for the preparative synthesis of optimized ACC substrates for HIV-1 protease and plasmin...
  40. pmc IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus
    Daniel Sojka
    Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic and Faculty of Biological Sciences, University of South Bohemia, Ceske Budejovice, Czech Republic
    Int J Parasitol 37:713-24. 2007
    ..The possible functions of IrAE in the gut digestive processes of I. ricinus are compared with those suggested for other hematophagous parasites...
  41. ncbi request reprint Computer-assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition
    Martha C A Laboissière
    Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias da Saude, Universidade de Brasilia, Campus Universitario Darcy Ribeiro, 70910 900 Brasilia, DF Brasil
    J Biol Chem 277:26623-31. 2002
    ..This technology can be applied to select for enhanced binding interactions at protein-protein interfaces and accelerate the process of protease inhibitor development...
  42. ncbi request reprint Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences
    Mekdes Debela
    Max Planck Institut fur Biochemie, Proteinase Research Group, Am Klopferspitz 18, D 82152 Martinsried, Germany
    J Biol Chem 281:25678-88. 2006
    ..The specificity profiles may lead to a better understanding of human tissue kallikrein functions and assist in identifying their physiological protein substrates as well as in designing more selective inhibitors...
  43. pmc Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII
    Barbara Leiting
    Department of Metabolic Disorders, Merck Research Laboratories, Mail code RY50G 236, P O Box 2000, Rahway, NJ 07065, USA
    Biochem J 371:525-32. 2003
    ..Selective DPP-IV and DPP-VII substrates were identified and they can be used to design selective inhibitors and probe further into the biology of these enzymes...
  44. ncbi request reprint Substrates of the prostate-specific serine protease prostase/KLK4 defined by positional-scanning peptide libraries
    Masazumi Matsumura
    Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA
    Prostate 62:1-13. 2005
    ..In this study, we sought to characterize the substrate specificity of KLK4 in order to gain insight into potential physiological roles of the enzyme...
  45. ncbi request reprint Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica
    Colin M Stack
    Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Sydney, New South Wales 2007, Australia
    J Biol Chem 283:9896-908. 2008
    ..The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite...
  46. ncbi request reprint A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms
    Angela L Williamson
    Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA
    J Biol Chem 279:35950-7. 2004
    ....
  47. pmc Quantitative and label-free technique for measuring protease activity and inhibition using a microfluidic cantilever array
    Digvijay A Raorane
    Department of Mechanical Engineering, University of California, Berkeley, California 94720, USA
    Nano Lett 8:2968-74. 2008
    ..58 x 10 (-6) M). Inhibition of surface-immobilized trypsin by soybean trypsin inhibitor (SBTI) was also observed using this system...
  48. pmc Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers
    Sylvia Herter
    Department of Biology, Amgen San Francisco, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Biochem J 390:125-36. 2005
    ....
  49. doi request reprint Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
    Mekdes Debela
    Max Planck Institut fur Biochemie, Proteinase Research Group, Am Klopferspitz 18, D 82152 Martinsried, Germany
    Biol Chem 389:623-32. 2008
    ..Interestingly, for KLK4, 5, and 7 extended charged surface regions were observed that most likely serve as exosites for physiological substrates...
  50. ncbi request reprint Expression and characterization of constitutively active human caspase-14
    Kyewhan Park
    Department of Oral Biology, University of Washington, Seattle, WA 98195, USA
    Biochem Biophys Res Commun 347:941-8. 2006
    ....

Research Grants7

  1. RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGY
    Charles Craik; Fiscal Year: 2007
    ..Expansion into the new Mission Bay campus has greatly strengthened the program by providing state of the art chemistry and chemical biology lab space. ..
  2. Targeting Allosteric Studies to Modulate Protein Interactions and Function
    Charles Craik; Fiscal Year: 2007
    ....
  3. A Technological Platform for the Identification of Serine Proteases in Cancer
    Charles Craik; Fiscal Year: 2009
    ..Support functions include the Molecular Foundry, the Microfabrication Laboratory, the Biomolecular Nanotechnology Center, facilities for manufacture of microarrays, and data management and integration. RELEVANCE ..
  4. Targeting Allosteric Studies to Modulate Protein Interactions and Function
    Charles Craik; Fiscal Year: 2009
    ....
  5. A Technological Platform for the Identification of Serine Proteases in Cancer
    CHARLES SCOTT CRAIK; Fiscal Year: 2010
    ..Support functions include the Molecular Foundry, the Microfabrication Laboratory, the Biomolecular Nanotechnology Center, facilities for manufacture of microarrays, and data management and integration. RELEVANCE ..