BORIS KHOLODENKOSummaryAffiliation: Thomas Jefferson University Country: USA Publications
Research Grants
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Publications
A domain-oriented approach to the reduction of combinatorial complexity in signal transduction networksHolger Conzelmann
Institute for System Dynamics and Control Engineering, University of Stuttgart, Pfaffenwaldring 9, 70569 Stuttgart, Germany
BMC Bioinformatics 7:34. 2006..The number of possible species grows exponentially with the number of different docking sites and can easily reach several millions. Models accounting for this combinatorial variety become impractical for many applications...- Cell-signalling dynamics in time and spaceBoris N Kholodenko
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA
Nat Rev Mol Cell Biol 7:165-76. 2006.... - Four-dimensional dynamics of MAPK information processing systemsBoris N Kholodenko
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Wiley Interdiscip Rev Syst Biol Med 1:28-44. 2009.... 
Giving space to cell signalingBoris N Kholodenko
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Cell 133:566-7. 2008..In this issue, Neves et al. (2008) report how the propagation of spatial information is controlled by the shape of hippocampal neurons and feedback and feed-forward motifs of the beta-adrenergic receptor signaling pathway...- Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascadesNick I Markevich
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA
J Cell Biol 164:353-9. 2004..Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity... - Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexityNikolay M Borisov
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Biophys J 89:951-66. 2005..Our domain-oriented approach drastically reduces the number of states, processes, and kinetic parameters to be considered for quantification of complex signaling networks that propagate distinct physiological responses... - Systems-level interactions between insulin-EGF networks amplify mitogenic signalingNikolay Borisov
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Mol Syst Biol 5:256. 2009..Our results show the feasibility of using computational models to identify key target combinations and predict complex cellular responses to a mixture of external cues... - PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cellsEdita Aksamitiene
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA
Cell Signal 22:1369-78. 2010..We discuss candidate proteins that can be involved in this activation circuitry and suggest that PDZ-Binding Kinase/T-LAK Cell-Originated Protein Kinase (PBK/TOPK) may play a role in mediating MEK-independent ERK activation... - Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycleNikolai P Kaimachnikov
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
FEBS J 276:4102-18. 2009..Our mathematical model helps to understand the puzzling experimental observations and suggests conditions where these different kinetic behaviors of SFKs can be tested experimentally... - Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascadesNick I Markevich
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Locust St, Philadelphia, PA 19107, USA
Mol Syst Biol 2:61. 2006..The finding of phosphorylation waves traveling with constant amplitude and high velocity may solve a long-standing enigma of survival signaling in developing neurons... - Trading the micro-world of combinatorial complexity for the macro-world of protein interaction domainsNikolay M Borisov
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA
Biosystems 83:152-66. 2006..Thus, our results greatly facilitate quantitative analysis and computational modeling of multi-protein signaling networks... 
Temperature dependence of the epidermal growth factor receptor signaling network can be accounted for by a kinetic modelGisela Moehren
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA
Biochemistry 41:306-20. 2002..A combination of high-resolution experimental monitoring and molecular level kinetic modeling made it possible to quantitatively account for the temperature dependence of the integrative signaling responses...- MAP kinase cascade signaling and endocytic trafficking: a marriage of convenience?Boris N Kholodenko
Dept of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
Trends Cell Biol 12:173-7. 2002..The proposed mechanism explains recent observations that MAPK activation can be strongly suppressed by various inhibitors of endocytosis... - Untangling the wires: a strategy to trace functional interactions in signaling and gene networksBoris N Kholodenko
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
Proc Natl Acad Sci U S A 99:12841-6. 2002..The method is tested and illustrated by using computer-generated responses of a modeled mitogen-activated protein kinase cascade and gene network... - Inference of signaling and gene regulatory networks by steady-state perturbation experiments: structure and accuracyMichael Andrec
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 8087, USA
J Theor Biol 232:427-41. 2005..Our ideas are illustrated using the mitogen-activated protein kinase (MAPK) signaling network as an example... - Modular interaction strengths in regulatory networks; an exampleFrank J Bruggeman
Dept Molecular Cell Physiology, BioCentrum Amsterdam, The Netherlands
Mol Biol Rep 29:57-61. 2002..This is illustrated by a calculation for an example of a modular biochemical network... - Ligand-dependent responses of the ErbB signaling network: experimental and modeling analysesMarc R Birtwistle
Department of Chemical Engineering, University of Delaware, Newark, DE, USA
Mol Syst Biol 3:144. 2007..Sensitivity analysis leads to the hypothesis that ERK activation is robust to parameter perturbation at high ligand doses, while Akt activation is not... - Untangling the signalling wiresBoris N Kholodenko
Nat Cell Biol 9:247-9. 2007 - Modular response analysis of cellular regulatory networksFrank J Bruggeman
Department of Molecular Cell Physiology, BioCentrum Amsterdam, De Boelelaan 1087, The Netherlands
J Theor Biol 218:507-20. 2002..The approach is illustrated by two examples: (i) mitogenic signalling through the mitogen-activated protein kinase cascade in the epidermal growth factor receptor network and (ii) regulation of ammonium assimilation in Escherichia coli... - The International Consortium on Systems Biology of Receptor Tyrosine Kinase Regulatory NetworksYoshiyuki Sakaki
Syst Biol (Stevenage) 152:53-4. 2005 - Oscillatory dynamics arising from competitive inhibition and multisite phosphorylationVijay Chickarmane
Keck Graduate Institute, 535 Watson Dr, Claremont, CA 91711, USA
J Theor Biol 244:68-76. 2007..In this case we obtain a ring oscillator. Both these networks illustrate the versatility of the multisite bistable network... - Bistability from double phosphorylation in signal transduction. Kinetic and structural requirementsFernando Ortega
Centre for Research in Theoretical Chemistry, Scientific Park of Barcelona, Spain
FEBS J 273:3915-26. 2006..Our results show that bistable behavior in covalent modification cascades relies not only on the structure and regulatory pattern of feedback/feedforward loops, but also on the kinetic characteristics of their component proteins... - Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite dataEduardo Sontag
Department of Mathematics, Rutgers University, Piscataway, NJ 08854, USA
Bioinformatics 20:1877-86. 2004..SUPPLEMENTARY INFORMATION: Supplementary material is available at http://www.dbi.tju.edu/bioinformatics2004.pdf.. - Control analysis for autonomously oscillating biochemical networksKarin A Reijenga
Department of Molecular Cell Physiology, BioCentrum Amsterdam, Faculty of Biology, Vrije Universiteit, NL-1081 HV Amsterdam, The Netherlands, EU
Biophys J 82:99-108. 2002..We show that the control of various oscillatory properties is distributed over the system enzymes in ways that differ among those properties. The models that are described in this paper can be accessed on http://jjj.biochem.sun.ac.za...
Research Grants
- Receptor Tyrosine Kinase Signaling NetworksBORIS KHOLODENKO; Fiscal Year: 2007....
- Mechanisms of Central Autonomic Orchestration of Blood PressureBORIS KHOLODENKO; Fiscal Year: 2007..The approach is to test these predictions at the level of effects on molecular processes involved in the physiological response, including feedback from gene regulatory responses. ..
- RECEPTOR TYROSINE KINASE SIGNALING IN THE LIVERBORIS KHOLODENKO; Fiscal Year: 2006....
- RECEPTOR TYROSINE KINASE SIGNALING IN THE LIVERBORIS KHOLODENKO; Fiscal Year: 2002....