WILLIAM HLAVACEK

Summary

Affiliation: Los Alamos National Laboratory
Country: USA

Publications

  1. pmc Modeling the effect of APC truncation on destruction complex function in colorectal cancer cells
    Dipak Barua
    Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
    PLoS Comput Biol 9:e1003217. 2013
  2. pmc Binding of nucleoid-associated protein fis to DNA is regulated by DNA breathing dynamics
    Kristy Nowak-Lovato
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
    PLoS Comput Biol 9:e1002881. 2013
  3. pmc Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling
    Matthew S Creamer
    Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    BMC Syst Biol 6:107. 2012
  4. pmc Hierarchical graphs for rule-based modeling of biochemical systems
    Nathan W Lemons
    Department of Mathematics and its Applications, Central European University, H 1051 Budapest, Hungary
    BMC Bioinformatics 12:45. 2011
  5. pmc RuleMonkey: software for stochastic simulation of rule-based models
    Joshua Colvin
    Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    BMC Bioinformatics 11:404. 2010
  6. ncbi request reprint Rules for modeling signal-transduction systems
    William S Hlavacek
    Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Sci STKE 2006:re6. 2006
  7. ncbi request reprint Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand-receptor interactions: theory and application to HIV treatment
    William S Hlavacek
    Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Math Biosci 176:185-202. 2002
  8. ncbi request reprint Kinetic proofreading in receptor-mediated transduction of cellular signals: receptor aggregation, partially activated receptors, and cytosolic messengers
    William S Hlavacek
    Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Mail Stop K710, T 10, Los Alamos, NM 87545, USA
    Bull Math Biol 64:887-911. 2002
  9. ncbi request reprint Investigation of early events in Fc epsilon RI-mediated signaling using a detailed mathematical model
    James R Faeder
    Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    J Immunol 170:3769-81. 2003
  10. ncbi request reprint Design of gene circuits: lessons from bacteria
    Michael E Wall
    Computer and Computational Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Rev Genet 5:34-42. 2004

Collaborators

Detail Information

Publications30

  1. pmc Modeling the effect of APC truncation on destruction complex function in colorectal cancer cells
    Dipak Barua
    Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
    PLoS Comput Biol 9:e1003217. 2013
    ..Specific inhibition of CK1ε is predicted to limit binding of β-catenin to truncated APC and thereby to reverse the effect of APC truncation...
  2. pmc Binding of nucleoid-associated protein fis to DNA is regulated by DNA breathing dynamics
    Kristy Nowak-Lovato
    Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
    PLoS Comput Biol 9:e1002881. 2013
    ..We conclude that Fis binding is associated with DNA breathing dynamics, which in turn may be regulated by various nucleotide modifications...
  3. pmc Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling
    Matthew S Creamer
    Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    BMC Syst Biol 6:107. 2012
    ..To overcome this problem, the rule-based modeling approach has been developed for representing interactions within signaling networks efficiently and compactly through coarse-graining of the chemical kinetics of molecular interactions...
  4. pmc Hierarchical graphs for rule-based modeling of biochemical systems
    Nathan W Lemons
    Department of Mathematics and its Applications, Central European University, H 1051 Budapest, Hungary
    BMC Bioinformatics 12:45. 2011
    ..A set of rules comprises an executable model that can be used to determine, through various means, the system-level dynamics of molecular interactions in a biochemical system...
  5. pmc RuleMonkey: software for stochastic simulation of rule-based models
    Joshua Colvin
    Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    BMC Bioinformatics 11:404. 2010
    ..The cost of these "network-free" simulation methods is independent of the number of reactions implied by rules. Software implementing such methods is now needed for the simulation and analysis of rule-based models of biochemical systems...
  6. ncbi request reprint Rules for modeling signal-transduction systems
    William S Hlavacek
    Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Sci STKE 2006:re6. 2006
    ..We also discuss rule visualization and exchange and the software available for rule-based modeling...
  7. ncbi request reprint Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand-receptor interactions: theory and application to HIV treatment
    William S Hlavacek
    Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Math Biosci 176:185-202. 2002
    ..We also consider the possibility that HIV is retained on B cells during therapy, which like FDCs also interact with HIV. We find that virus associated with B cells is unlikely to persist during therapy...
  8. ncbi request reprint Kinetic proofreading in receptor-mediated transduction of cellular signals: receptor aggregation, partially activated receptors, and cytosolic messengers
    William S Hlavacek
    Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Mail Stop K710, T 10, Los Alamos, NM 87545, USA
    Bull Math Biol 64:887-911. 2002
    ....
  9. ncbi request reprint Investigation of early events in Fc epsilon RI-mediated signaling using a detailed mathematical model
    James R Faeder
    Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    J Immunol 170:3769-81. 2003
    ..We also show that although the beta ITAM acts to amplify signaling in experimental systems where its role has been investigated, there are conditions under which the beta ITAM will act as an inhibitor...
  10. ncbi request reprint Design of gene circuits: lessons from bacteria
    Michael E Wall
    Computer and Computational Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Rev Genet 5:34-42. 2004
  11. ncbi request reprint Kinetic proofreading model
    Byron Goldstein
    Theoretical Biology and Biophysics Group, T 10 MS K710, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 875435, USA
    Adv Exp Med Biol 640:82-94. 2008
    ..We review experiments designed to test for kinetic proofreading and models that exhibit kinetic proofreading...
  12. ncbi request reprint Mathematical and computational models of immune-receptor signalling
    Byron Goldstein
    Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Rev Immunol 4:445-56. 2004
  13. ncbi request reprint Multiple functions of a feed-forward-loop gene circuit
    Michael E Wall
    Computer and Computational Sciences Division, Mail Stop B256, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    J Mol Biol 349:501-14. 2005
    ..Our results provide a catalog of functions for a class of FFL circuits, whose subclasses have different breadths of possible behaviors and different typical behaviors...
  14. ncbi request reprint Modeling the early signaling events mediated by FcepsilonRI
    Byron Goldstein
    Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Mol Immunol 38:1213-9. 2002
    ....
  15. ncbi request reprint BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
    Michael L Blinov
    Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Bioinformatics 20:3289-91. 2004
    ..Models that can be generated are relevant for rational drug discovery, analysis of proteomic data and mechanistic studies of signal transduction...
  16. ncbi request reprint Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism
    Ilya Nemenman
    CCS 3, MS B256, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Ann N Y Acad Sci 1115:102-15. 2007
    ..We find that the performance of ARACNE on metabolic data is comparable to that on gene expression data...
  17. pmc Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell-surface receptor aggregates
    Michael I Monine
    Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
    Biophys J 98:48-56. 2010
    ..Steric effects that limit receptor aggregation and transient formation of small receptor aggregates may also be important...
  18. pmc On imposing detailed balance in complex reaction mechanisms
    Jin Yang
    Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, New Mexico, USA
    Biophys J 91:1136-41. 2006
  19. ncbi request reprint Prediction of oxidoreductase-catalyzed reactions based on atomic properties of metabolites
    Fangping Mu
    Theoretical Biology and Biophysics Group, Theoretical Division Los Alamos, NM 87545, USA
    Bioinformatics 22:3082-8. 2006
    ..To address this challenge, we investigate how machine learning can be used to predict potential substrates and products of oxidoreductase-catalyzed reactions...
  20. ncbi request reprint A network model of early events in epidermal growth factor receptor signaling that accounts for combinatorial complexity
    Michael L Blinov
    Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Biosystems 83:136-51. 2006
    ..A comparison of the two models suggests experiments that could lead to mechanistic insights about competition among adapter proteins for EGFR binding sites and the role of EGFR monomers in signal transduction...
  21. ncbi request reprint Carbon-fate maps for metabolic reactions
    Fangping Mu
    Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Bioinformatics 23:3193-9. 2007
    ..Analysis of isotope labeling patterns requires knowledge of the fates of individual atoms and moieties in reactions, which can be difficult to collect in a useful form when considering a large number of enzymatic reactions...
  22. ncbi request reprint The complexity of cell signaling and the need for a new mechanics
    William S Hlavacek
    Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Sci Signal 2:pe46. 2009
    ..Newly available data support the idea that this mechanics should enable one to track the site-specific details of molecular interactions in a model, such as the phosphorylation status of individual amino acid residues within a protein...
  23. ncbi request reprint Design principles for regulator gene expression in a repressible gene circuit
    Michael E Wall
    Computer and Computational Sciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    J Mol Biol 332:861-76. 2003
    ..These theoretical results provide a rationale for autoregulation of regulator genes in repressible gene circuits and lead to testable predictions, which we have compared with data available in the literature and electronic databases...
  24. ncbi request reprint The complexity of complexes in signal transduction
    William S Hlavacek
    Theoretical Biology and Biophysics Group T 10, Theoretical Division, Mail Stop K710, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Biotechnol Bioeng 84:783-94. 2003
    ..Here, we review the role of multicomponent complexes in signal transduction and advocate the use of mathematical models that incorporate detail at the level of molecular domains to study this important aspect of cellular signaling...
  25. ncbi request reprint 'On-the-fly' or 'generate-first' modeling?
    Michael L Blinov
    Nat Biotechnol 23:1344-5; author reply 1345. 2005
  26. ncbi request reprint A quantitative approach for studying IgE-FcepsilonRI aggregation
    Richard G Posner
    Department of Chemistry, Northern Arizona University, Flagstaff, AZ 86011 5698, USA
    Mol Immunol 38:1221-8. 2002
    ..We show that the magnitude of the cellular response is dramatically increased as the valence of our ligand is raised from two to three...
  27. ncbi request reprint Interaction of a monoclonal IgE-specific antibody with cell-surface IgE-Fc epsilon RI: characterization of equilibrium binding and secretory response
    Richard G Posner
    Department of Biology, Northern Arizona University, Flagstaff, Arizona 86011, USA
    Biochemistry 43:11352-60. 2004
    ..There is no simple relationship between receptor aggregation at equilibrium and the degranulation response. Further studies are needed to establish how 23G3-induced aggregation of IgE-FcepsilonRI correlates with cellular responses...
  28. ncbi request reprint Depicting signaling cascades
    Michael L Blinov
    Nat Biotechnol 24:137-8; author reply 138. 2006
  29. pmc Q-bio 2007: a watershed moment in modern biology
    Jeremy S Edwards
    Molecular Genetics and Microbiology, Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, and Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM, USA
    Mol Syst Biol 3:148. 2007

Research Grants5

  1. System-wide Study of Transcriptional Control of Metabolism
    WILLIAM HLAVACEK; Fiscal Year: 2007
    ..While important in its own right, especially in view of the pathogenic nature of B. anthracis, this research would also represent an important test bed for a subsequent study of metabolic diseases in higher animals, including humans. ..
  2. COMPUTATIONAL TOOLS FOR RULE-BASED MODELING OF BIOCHEMICAL SYSTEMS
    WILLIAM HLAVACEK; Fiscal Year: 2007
    ..An important capability we wish to achieve is the ability to model a significant fraction of the known human signal-transduction systems. ..
  3. COMPUTATIONAL TOOLS FOR RULE-BASED MODELING OF BIOCHEMICAL SYSTEMS
    WILLIAM HLAVACEK; Fiscal Year: 2009
    ..An important capability we wish to achieve is the ability to model a significant fraction of the known human signal-transduction systems. ..