Navigation

Researchers at UCD

researcher

Boris Kholodenko

Deputy Director of The Systems Biology Centre

Conway Institute
Systems Biology Ireland
Temple Street
Dublin 1

Tel: +353 1 7166304
Email: boris.kholodenko@ucd.ie

Biography

Expertise:

  • Mathematical modelling of cellular processes
  • Spatiotemporal dynamics of signalling networks
  • Network interference

Prof. Boris Kholodenko is SFI Stokes Professor of Systems Biology at Systems Biology Ireland and UCD Conway Institute. He is also Adjunct Professor at Thomas Jefferson University, Philadelphia, USA. Kholodenko is the author of more than 220 publications on spatio-temporal dynamics and control analysis of cellular signalling and metabolic networks, and is a founding chairman of the International Consortium on Systems Biology of Receptor Tyrosine Kinase Regulatory Networks. He is widely recognised as a leader in the field of Systems Biology and predictive models of cellular functions and his work is been highly influential in shaping the field of systems biology as it is known today.

Kholodenko graduated with a Ph.D. in Biophysics from the Moscow Institute of Physics and Technology, Russia. He was then invited to work in the laboratory of Anatol M. Zhabotinsky, known for his studies of the Belousov-Zhabotinsky reaction. Afterwards, Kholodenko worked at the Moscow State University, where he has made crucial contributions to metabolic control analysis, such as the development of the control analysis of cellular systems involving direct enzyme-enzyme interactions, restricted diffusion and information transfer. Because of his unique combination of expertise in biochemistry, physical chemistry and mathematics, Kholodenko was invited to the Free University of Amsterdam, the Netherlands, by Hans Westerhoff. In 1997, Kholodenko joined the faculty of Thomas Jefferson University, where his group along with Dr. Jan Hoek and others developed the first systems biology model of the Epidermal Growth Factor Receptor signalling pathway. In 2009, he moved to Dublin to organise together with Prof Kolch, Systems Biology Ireland at UCD. 

Key Research Highlights

  • Pioneered Metabolic Control Analysis of cellular systems with enzyme and substrate sequestration, variable system volume, protein-protein interactions, restricted diffusion and direct transfer of metabolites (Kholodenko & Westerhoff, FEBS Lett. 1993, 320:71, 86 citations).
  • Pioneered a combined experimental and computational (based on the chemical kinetic equation theory) approach to the analysis of signal transduction networks and developed the first data-driven, mechanistic model of the Epidermal Growth Factor Receptor signalling pathway (Kholodenko et al J Biol Chem, 274:30169, 1999, 557 citations in Google Scholar).
  • Predicted the existence of intracellular spatial gradients of signalling protein activities, which later were discovered experimentally (Brown & Kholodenko, FEBS Lett, 457:452, 1999, 179 citations). My review on cell signalling dynamics in space and time proved influential in the field (Kholodenko, B.N. Nat Rev Mol Cell Biol. 2006, 7:165. 903 citations).
  • Predicted that ultrasensitivity and negative feedback in Mitogen Activated Protein Kinase cascades can bring about sustained oscillations, which were later observed experimentally (Kholodenko B.N. Europ. J. Biochem, 267:1583, 2000, 624 citations).
  • Demonstrated that bistability can arise from multisite phosphorylation (Markevich et al, J Cell Biol. 164:353, 2004, 532 citations). This work introduced novel paradigm that multisite covalent modification can induce bistable switches, motivating a large number of theoretical and experimental studies.
  • Developed Modular Response Analysis that can unravel interaction ¿maps¿ in signalling and gene networks from perturbation responses (Kholodenko et al, PNAS 2002, 20:12841, 377 citations).
  • Pioneered network modelling that related cytoplasmic signalling with the expression of immediate early genes (Nakakuki et al, Cell 141:884, 2010, 133 citations, reviewed in Kholodenko et al, Nat Rev Mol Cell Biol. 11:414, 2010, 372 citations).
  • Showed that drug resistance emerges from kinase dimerization, which is an obligatory step in the physiological and oncogenic activation of numerous kinases (Kholodenko B.N. Cell reports, 2015, 12:1939). Predicted that two inhibitors against the same kinase, while ineffective on their own, can abolish resistance when combined.
  • A proof of concept demonstration that experimentally validated signalling network models can serve as information-rich biomarkers for personalised patient stratification (Fey et al, Sci Sign 8, ra130, 2015).

Publications

 

Book Chapters

Fey, D; Croucher, DR; Kolch, W; Kholodenko, BN (2012) 'Understanding Cell Fate Decisions by Identifying Crucial System Dynamics' In: D'Onofrio, A; Cerrai, P; Gandolfi, A (eds). New Challenges for Cancer Systems Biomedicine, SIMAI Springer Series. Heidelberg: Springer. , pp.83-104 [Details]
 

Peer Reviewed Journals

Nguyen, L.K.a and Matallanas, D.G.a and Romano, D.a and Kholodenko, B.N.a b c and Kolch, W.a b c (2015) 'Competing to coordinate cell fate decisions the MST2-Raf-1 signaling device'. Cell Cycle, 14 (2):189-199. Available Online [DOI] [Details]
Volinsky, N., McCarthy, C. J., Von Kriegsheim, A., Saban, N., Okada-Hatakeyama, M., Kolch, W., Kholodenko, B. N. (2015) 'Signalling mechanisms regulating phenotypic changes in breast cancer cells'. Biosci Rep, . [Details]
Ryu, H; Chung, M; Dobrzynski, M; Fey, D; Blum, Y; Lee, SS; Peter, M; Kholodenko, BN; Jeon, NL; Pertz, O (2015) 'Frequency modulation of ERK activation dynamics rewires cell fate'. Molecular Systems Biology, 11 :838. [DOI] [Details]
Fey, D; Halasz, M; Dreidax, D; Kennedy, SP; Hastings, JF; Rauch, N; Munoz, AG; Pilkington, R; Fischer, M; Westermann, F; Kolch, W; Kholodenko, BN; Croucher, DR. (2015) 'Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients'. Science signaling, 8 (408). [DOI] [Details]
Jambrina, PG; Rauch, N; Pilkington, R; Rybakova, K; Nguyen, LK; Kholodenko, BN; Buchete, NV; Kolch, W; Rosta, E (2016) 'Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation'. Angewandte Chemie International Edition, 55 (3):983-986. Available Online [DOI] [Details]
Sanchez-Sanz, G; Tywoniuk, B; Matallanas, D; Romano, D; Nguyen, LK; Kholodenko, BN; Rosta, E; Kolch, W; Buchete, NV (2016) 'SARAH Domain-mediated MST2-RASSF Dimeric Interactions'. PLoS Computational Biology, 12 (10):e1005051. Available Online [DOI] [Details]
Byrne KM, Monsefi N;Dawson JC;Degasperi A;Bukowski-Wills JC;Volinsky N;Dobrzy¿¿ski M;Birtwistle MR;Tsyganov MA;Kiyatkin A;Kida K;Finch AJ;Carragher NO;Kolch W;Nguyen LK;von Kriegsheim A;Kholodenko BN (2016) 'Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches'. Cell systems, 2 (1):38-48. [DOI] [Details]
Bastiaens, P. and Birtwistle, M.R. and Blüthgen, N. and Bruggeman, F.J. and Cho, K.-H. and Cosentino, C. and De La Fuente, A. and Hoek, J.B. and Kiyatkin, A. and Klamt, S. and Kolch, W. and Legewie, S. and Mendes, P. and Naka, T. and Santra, T. and Sontag, E. and Westerhoff, H.V. and Kholodenko, B.N. (2015) 'Silence on the relevant literature and errors in implementation'. Nature Biotechnology, 33 (4):336-339. Available Online [DOI] [Details]
Jambrina PG, Rauch N;Pilkington R;Rybakova K;Nguyen LK;Kholodenko BN;Buchete NV;Kolch W;Rosta E (2015) 'Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation'. Angewandte Chemie International Edition, . [DOI] [Details]
Fey D, Halasz M;Dreidax D;Kennedy SP;Hastings JF;Rauch N;Munoz AG;Pilkington R;Fischer M;Westermann F;Kolch W;Kholodenko BN;Croucher DR (2015) 'Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients'. Science signaling, 8 (408). [DOI] [Details]
Nagashima T1, Inoue N, Yumoto N, Saeki Y, Magi S, Volinsky N, Sorkin A, Kholodenko BN, Okada-Hatakeyama M. (2015) 'Feedforward regulation of mRNA stability by prolonged extracellular signal-regulated kinase activity'. FEBS Journal, . [DOI] [Details]
Nguyen LK, Cavadas MA, Scholz CC, Fitzpatrick SF, Bruning U, Cummins EP, Tambuwala MM, Manresa MC, Kholodenko BN, Taylor CT, Cheong A. (2015) 'A dynamic model of the hypoxia-inducible factor 1a (HIF-1a) network'. Journal of Cell Science, . [DOI] [Details]
Nguyen LK, Cavadas MA, Kholodenko BN, Frank TD, Cheong A. (2015) 'Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate'. Cellular and Molecular Life Sciences, . [DOI] [Details]
Nguyen LK, Degasperi A, Cotter P, Kholodenko BN. (2015) 'DYVIPAC: an integrated analysis and visualisation framework to probe multi-dimensional biological networks'. Scientific Reports, . [DOI] [Details]
Kholodenko BN (2015) 'Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects'. Cell Reports, . [DOI] [Details]
Nguyen LK, Kholodenko BN. (2015) 'Feedback regulation in cell signalling: Lessons for cancer therapeutics'. Seminars in Cell and Developmental Biology, . [DOI] [Details]
Milewska M, Romano D;Herrero A;Guerriero ML;Birtwistle M;Quehenberger F;Hatzl S;Kholodenko BN;Segatto O;Kolch W;Zebisch A (2015) 'Mitogen-Inducible Gene-6 Mediates Feedback Inhibition from Mutated BRAF towards the Epidermal Growth Factor Receptor and Thereby Limits Malignant Transformation'. PLoS ONE, 10 (6). [DOI] [Details]
Nguyen LK, Matallanas DG;Romano D;Kholodenko BN;Kolch W (2015) 'Competing to coordinate cell fate decisions: the MST2-Raf-1 signaling device'. Cell Cycle, 14 (2):189-199. [DOI] [Details]
Tortolina L, Duffy DJ;Maffei M;Castagnino N;Carmody AM;Kolch W;Kholodenko BN;De Ambrosi C;Barla A;Biganzoli EM;Nencioni A;Patrone F;Ballestrero A;Zoppoli G;Verri A;Parodi S (2015) 'Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies'. Oncotarget, 6 (7):5041-5058. [Details]
Volinsky N, McCarthy CJ;von Kriegsheim A;Saban N;Okada-Hatakeyama M;Kolch W;Kholodenko BN (2015) 'Signalling mechanisms regulating phenotypic changes in breast cancer cells'. Bioscience Reports, 35 (2). [DOI] [Details]
Kim TH, Monsefi N;Song JH;von Kriegsheim A;Vandamme D;Pertz O;Kholodenko BN;Kolch W;Cho KH (2015) 'Network-based identification of feedback modules that control RhoA activity and cell migration'. Journal of molecular cell biology, 7 (3):242-252. [DOI] [Details]
Varusai TM, Kolch W;Kholodenko BN;Nguyen LK (2015) 'Protein-protein interactions generate hidden feedback and feed-forward loops to trigger bistable switches, oscillations and biphasic dose-responses'. Molecular BioSystems, 11 (10):2750-2762. [DOI] [Details]
Kolch, W; Halasz, M; Granovskaya, M; Kholodenko, BN. (2015) 'The dynamic control of signal transduction networks in cancer cells'. Nature Reviews Cancer, 15 (9):515-527. Available Online [DOI] [Details]
Sanchez-Sanz, G; Matallanas, D; Nguyen, LK; Kholodenko, BN; Rosta, E; Kolch, W; Buchete, NV (2016) 'MST2-RASSF protein-protein interactions through SARAH domains'. Briefings in Bioinformatics, 17 (4):593-602. Available Online [DOI] [Details]
Romano D, Nguyen LK, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W (2014) 'Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling'. Nature Cell Biology, 16 (7):673-684. [DOI] [Details]
Vandamme D, Minke BA;Fitzmaurice W;Kholodenko BN;Kolch W (2014) 'Systems biology-embedded target validation: improving efficacy in drug discovery'. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 6 (1):1-11. [DOI] [Details]
Nguyen LK, Dobrzy¿¿ski M;Fey D;Kholodenko BN (2014) 'Polyubiquitin chain assembly and organization determine the dynamics of protein activation and degradation'. Frontiers in Physiology, 5 . [DOI] [Details]
Santra T, Kolch W;Kholodenko BN (2014) 'Navigating the multilayered organization of eukaryotic signaling: a new trend in data integration'. PLoS Computational Biology, 10 (2). [DOI] [Details]
Editor's Choice: Romano D, Nguyen LK*, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W. (*Lead modelling author) (2014) 'Switching Partners by Phosphorylation'. Science signaling, . [Details]
Dobrzyſski M, Nguyen LK, Birtwistle MR, von Kriegsheim A, Blanco Fernández A, Cheong A, Kolch W, Kholodenko BN (2014) 'Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses'. Journal of the Royal Society Interface, 11 (98). [DOI] [Details]
Vandamme, D. and Minke, B.A. and Fitzmaurice, W. and Kholodenko, B.N. and Kolch, W. (2014) 'Systems biology-embedded target validation: Improving efficacy in drug discovery'. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 6 (1):1-11. Available Online [DOI] [Details]
Santra, T. and Kolch, W. and Kholodenko, B.N. (2014) 'Navigating the Multilayered Organization of Eukaryotic Signaling: A New Trend in Data Integration'. PLoS Computational Biology, 10 (2). Available Online [DOI] [Details]
Romano, D; Nguyen, LK; Matallanas, D; Halasz, M; Doherty, C; Kholodenko, BN; Kolch, W. (2014) 'Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling'. Nature Cell Biology, 16 (7):673-684. Available Online [DOI] [Details]
Degasperi, A. and Birtwistle, M.R. and Volinsky, N. and Rauch, J. and Kolch, W. and Kholodenko, B.N. (2014) 'Evaluating strategies to normalise biological replicates of western blot data'. PLoS ONE, 9 (1). Available Online [DOI] [Details]
Dobrzyſski, M. and Nguyen, L.K. and Birtwistle, M.R. and Von Kriegsheim, A. and Fernández, A.B. and Cheong, A. and Kolch, W. and Kholodenko, B.N. (2014) 'Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses'. Journal of the Royal Society Interface, 11 (98). Available Online [DOI] [Details]
Song, J.-H. and Huels, D.J. and Ridgway, R.A. and Sansom, O.J. and Kholodenko, B.N. and Kolch, W. and Cho, K.-H. (2014) 'The APC network regulates the removal of mutated cells from colonic crypts'. Cell Reports, 7 (1):94-103. Available Online [DOI] [Details]
Editor's Choice: Romano D, Nguyen LK*, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W. (*Lead modelling author) (2014) 'Switching Partners by Phosphorylation'. Science signaling, 7 (335):199. [DOI] [Details]
Romano D, Nguyen LK*, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W. (*Lead modelling author.) (2014) 'Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling'. Nature Cell Biology, 16 (7):673-684. [DOI] [Details]
Degasperi, A; Birtwistle, MR; Volinsky, N; Rauch, J; Kolch, W; Kholodenko, BN (2014) 'Evaluating Strategies to Normalise Biological Replicates of Western Blot Data'. PLoS ONE, 9 (1). Link to full text [Details]
Kolch W, Kholodenko B (2013) 'Systems medicine: opportunities and challenges for systems biology approaches'. FEBS Journal, . [DOI] [Details]
Nguyen LK, Cavadas MAS, Scholz CC, Fitzpatrick SF, Bruning U, Cummins EP, Tambuwala MM, Manresa MC, Kholodenko BN, Taylor CT and Cheong A (2013) 'A dynamic model of the hypoxia-inducible factor 1-alpha (HIF-1α) network'. Journal of Cell Science, . [Details]
Nguyen, L.K., Matallanas, D., Croucher, D.R., von Kriegsheim, A, Kholodenko, B.N. (2013) 'Signalling by protein phosphatases and drug development: a systems-centred view'. FEBS Journal, 280 (2):751-65. Available Online [DOI] [Details]
Nguyen, L.K., Cavadas, M.A.S., Scholz, C.C., Fitzpatrick, S.F., Bruning, U., Cummins, E.P., Tambuwala, M.T., Manresa, M.C., Kholodenko, B.N., Taylor, C.T., & Cheong, A. (2013) 'A dynamic model of the hypoxia-inducible factor (HIF) network'. Journal of Cell Science, 126 (Pt 6):1454-63. Available Online [DOI] [Details]
Nguyen, L.K., Kolch, W., Kholodenko, B.N. (2013) 'When ubiquitinylation meets phosphorylation: the systems biology of MAP kinase'. Cell Communication and Signaling, 11 (52). Available Online [DOI] [Details]
Baljuls, A., Kholodenko, B. N., Kolch, W. (2013) 'It takes two to tango--signalling by dimeric Raf kinases'. Mol Biosyst, 9 (4):551-8. [Details]
Kolch, W., Kholodenko, B. (2013) 'Systems medicine: opportunities and challenges for systems biology approaches'. FEBS J, . [Details]
Nguyen, L. K., Kolch, W., Kholodenko, B. N. (2013) 'When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling'. Cell Commun Signal, 11 :52. [Details]
Nikonova, E., Tsyganov, M. A., Kolch, W., Fey, D., Kholodenko, B. N. (2013) 'Control of the G-protein cascade dynamics by GDP dissociation inhibitors'. Mol Biosyst, 9 (10):2454-62. [Details]
Reiterer, V., Fey, D., Kolch, W., Kholodenko, B. N., Farhan, H. (2013) 'Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2'. Proceedings of the National Academy of Sciences USA, 110 (31):43. [Details]
Santra, T., Kolch, W., Kholodenko, B. N. (2013) 'Integrating Bayesian variable selection with Modular Response Analysis to infer biochemical network topology'. BMC Syst Biol, 7 :57. [Details]
Vandamme, D., Fitzmaurice, W., Kholodenko, B., Kolch, W. (2013) 'Systems medicine: helping us understand the complexity of disease'. QJM, 106 (10):891-5. [Details]
Vandamme, D., Minke, B. A., Fitzmaurice, W., Kholodenko, B. N., Kolch, W. (2013) 'Systems biology-embedded target validation: improving efficacy in drug discovery'. Wiley Interdiscip Rev Syst Biol Med, . [Details]
Nguyen LK, Cavadas MA, Scholz CC, Fitzpatrick SF, Bruning U, Cummins EP, Tambuwala MM, Manresa MC, Kholodenko BN, Taylor CT, Cheong A. (2013) 'A dynamic model of the hypoxia-inducible factor 1-alpha (HIF-1α) network'. Journal of Cell Science, . Available Online [Details]
Baljuls A, Kholodenko BN, Kolch W. (2013) 'It takes two to tango--signalling by dimeric Raf kinases'. Molecular BioSystems, . [Details]
Santra T, Kolch W, Kholodenko BN. (2013) 'Integrating Bayesian variable selection with Modular Response Analysis to infer biochemical network topology'. BMC systems biology, . [Details]
Nguyen LK, Cavadas MA, Scholz CC, Fitzpatrick SF, Bruning U, Cummins EP, Tambuwala MM, Manresa MC, Kholodenko BN, Taylor CT, Cheong A (2013) 'A dynamic model of the hypoxia-inducible factor 1-alpha (HIF-1a) network'. Journal of Cell Science, . [DOI] Link to full text [Details]
Santra T, Kolch W, Kholodenko BN (2013) 'Integrating Bayesian variable selection with Modular Response Analysis to infer biochemical network topology'. BMC Systems Biology, 7 . [DOI] Link to full text [Details]
Reiterer V, Fey D, Kolch W, Kholodenko BN, Farhan H (2013) 'Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2'. Proceedings of the National Academy of Sciences of the United States of America, 110 (31):1-43. [DOI] Link to full text [Details]
Nikonova E, Tsyganov MA, Kolch W, Fey D, Kholodenko BN (2013) 'Control of the G-protein cascade dynamics by GDP dissociation inhibitors'. Molecular BioSystems, 9 (10):2454-2462. [DOI] Link to full text [Details]
Nguyen LK, Kolch W, Kholodenko BN (2013) 'When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling'. Journal of Cell Communication and Signaling, 11 . [DOI] [Details]
Volinsky N, Kholodenko BN (2013) 'Complexity of receptor tyrosine kinase signal processing'. Cold Spring Harbor perspectives in biology, 5 (8). [DOI] [Details]
Vandamme D, Fitzmaurice W, Kholodenko B, Kolch W (2013) 'Systems medicine: helping us understand the complexity of disease'. Qjm-An International Journal Of Medicine, 106 (10):891-895. [DOI] Link to full text [Details]
Frank TD, Cheong A, Okada-Hatakeyama M, Kholodenko BN (2012) 'Catching transcriptional regulation by thermostatistical modeling'. Physical Biology, 9 (4). [DOI] Link to full text [Details]
Birtwistle, MR,Rauch, J,Kiyatkin, A,Aksamitiene, E,Dobrzynski, M,Hoek, JB,Kolch, W,Ogunnaike, BA,Kholodenko, BN (2012) 'Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise'. BMC Systems Biology, 6 . [DOI] [Details]
Birtwistle, MR,von Kriegsheim, A,Dobrzynski, M,Kholodenko, BN,Kolch, W (2012) 'Mammalian protein expression noise: scaling principles and the implications for knockdown experiments'. Molecular BioSystems, 8 :3068-3076. [DOI] [Details]
Frank, TD,Cheong, A,Okada-Hatakeyama, M,Kholodenko, BN (2012) 'Catching transcriptional regulation by thermostatistical modeling'. Physical Biology, 9 . [DOI] [Details]
Frank, TD,Carmody, AM,Kholodenko, BN (2012) 'Versatility of Cooperative Transcriptional Activation: A Thermodynamical Modeling Analysis for Greater-Than-Additive and Less-Than-Additive Effects'. PLoS ONE, 7 . [DOI] [Details]
Aksamitiene, E,Kiyatkin, A,Kholodenko, BN (2012) 'Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance'. Biochemical Society Transactions, 40 :139-146. [DOI] [Details]
Tsyganov, MA,Kolch, W,Kholodenko, BN (2012) 'The topology design principles that determine the spatiotemporal dynamics of G-protein cascades'. Molecular BioSystems, 8 :730-743. [DOI] [Details]
Dobrzynski, M.*, Fey, D.*, Nguyen, L.K.*, Kholodenko, B.N. (*co-first author) (2012) 'Bimodal Protein Distribution in Heterogeneous Oscillating Systems'. Lecture Notes in Computer Science, (7605):17-28. Available Online [Details]
Birtwistle, M. R., Rauch, J., Kiyatkin, A., Aksamitiene, E., Dobrzynski, M., Hoek, J. B., Kolch, W., Ogunnaike, B. A., Kholodenko, B. N. (2012) 'Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise'. BMC Syst Biol, 6 :109. [Details]
Birtwistle, M. R., von Kriegsheim, A., Dobrzynski, M., Kholodenko, B. N., Kolch, W. (2012) 'Mammalian protein expression noise: scaling principles and the implications for knockdown experiments'. Mol Biosyst, 8 (11):3068-76. [Details]
Fey, D., Croucher, D. R., Kolch, W., Kholodenko, B. N. (2012) 'Crosstalk and signaling switches in mitogen-activated protein kinase cascades'. Front Physiol, 3 :355. [Details]
Kholodenko, B., Yaffe, M. B., Kolch, W. (2012) 'Computational approaches for analyzing information flow in biological networks'. Science signaling, 5 (220). [DOI] [Details]
Santra, T., Kholodenko, B., Kolch, W. (2012) 'An integrated bayesian framework for identifying phosphorylation networks in stimulated cells'. Adv Exp Med Biol, 736 :59-80. [Details]
Tsyganov, M. A., Kolch, W., Kholodenko, B. N. (2012) 'The topology design principles that determine the spatiotemporal dynamics of G-protein cascades'. Mol Biosyst, 8 (3):730-43. [Details]
Birtwistle, M. R., Rauch, J., Kiyatkin, A., Aksamitiene, E., Dobrzynski, M., Hoek, J. B., Kolch, W., Ogunnaike, B. A., Kholodenko, B. N. (2012) 'Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise'. BMC Syst Biol, 6 :109. Available Online [Details]
Nguyen, L. K., Matallanas, D., Croucher, D. R., von Kriegsheim, A., Kholodenko, B. N. (2012) 'Signalling by protein phosphatases and drug development: a systems-centred view'. FEBS Journal, . Available Online [Details]
Fey, D., Croucher, D. R., Kolch, W., Kholodenko, B. N. (2012) 'Crosstalk and signaling switches in mitogen-activated protein kinase cascades'. Front Physiology, 3 :355. Available Online [DOI] [Details]
Fey, D; Croucher, DR; Kolch, W; Kholodenko, BN (2012) 'Crosstalk and Signaling Switches in Mitogen-Activated Protein Kinase Cascades'. Frontiers in physiology, 3 :355. [Details]
Birtwistle, M.R. and von Kriegsheim, A. and Dobrzy\'nski, M. and Kholodenko, B. and Kolch, W. (2012) 'Mammalian Protein Expression Noise: Scaling Principles and the Implications for Knockdown Experiments'. Molecular BioSystems, 8 (11):3068-3076. Available Online [DOI] [Details]
Birtwistle, MR; Rauch, J; Kiyatkin, A; Aksamitiene, E; Dobrzyński, M; Hoek, JB; Kolch, W; Ogunnaike, BA; Kholodenko, BN (2012) 'Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise'. BMC systems biology, 6 (1):109. Available Online [DOI] [Details]
Frank, TD; Cheong, A; Okada-Hatakeyama, M; Kholodenko, BN (2012) 'Catching transcriptional regulation by thermostatistical modeling'. Physical Biology, . [DOI] [Details]
Frank, T.D., Carmody, A.M., Kholodenko, B.N. (2012) 'Versatility of cooperative transcriptional activation'. PLoS ONE, . [Details]
Fey D, Croucher DR, Kolch W, Kholodenko BN (2012) 'Crosstalk and signaling switches in mitogen-activated protein kinase cascades'. Frontiers in Physiology, 3 . [DOI] Link to full text [Details]
Tsyganov MA, Kolch W, Kholodenko BN (2012) 'The topology design principles that determine the spatiotemporal dynamics of G-protein cascades'. Molecular BioSystems, 8 (3):730-743. [DOI] Link to full text [Details]
Aksamitiene E, Kiyatkin A, Kholodenko BN (2012) 'Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance'. Biochemical Society Transactions, 40 (1):139-146. [DOI] Link to full text [Details]
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzynski M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN (2012) 'Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise'. BMC systems biology, 6 . [DOI] Link to full text [Details]
Birtwistle MR, Kriegsheim Av, DobrzyÅski M, Kholodenko BN, Kolch W (2012) 'Mammalian protein expression noise: scaling principles and the implications for knockdown experiments'. Molecular BioSystems, 8 (11):3068-3076. [DOI] Link to full text [Details]
Santra T, Kholodenko B, Kolch W (2012) 'An integrated Bayesian framework for identifying phosphorylation networks in stimulated cells'. Frontiers in Modeling and Control of Breathing, 736 :59-80. [DOI] Link to full text [Details]
Nguyen LK, Matallanas D, Croucher DR, von Kriegsheim A, Kholodenko BN (2012) 'Signalling by protein phosphatases and drug development: a systems-centred view'. FEBS Journal, . [DOI] Link to full text [Details]
Frank TD, Carmody AM, Kholodenko BN (2012) 'Versatility of cooperative transcriptional activation: a thermodynamical modeling analysis for greater-than-additive and less-than-additive effects'. PLoS ONE, 7 (4). [DOI] Link to full text [Details]
Kholodenko B, Yaffe MB, Kolch W (2012) 'Computational approaches for analyzing information flow in biological networks'. Science signaling, 5 (220). [DOI] [Details]
Nguyen LK, Munoz-García J, Maccario H, Ciechanover A, Kolch W, Kholodenko BN (2011) 'Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system'. PLoS Computational Biology, 7 (12). [DOI] Link to full text [Details]
Nguyen, LK,Munoz-Garcia, J,Maccario, H,Ciechanover, A,Kolch, W,Kholodenko, BN (2011) 'Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System'. PLoS Computational Biology, 7 . [DOI] [Details]
Nguyen, L.K., Muñoz-García, J., Maccario, H., Ciechanover, A., Kolch W., & Kholodenko, B.K. (2011) 'Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system'. PLoS Computational Biology, 7 (12):e1002317. Available Online [Details]
Aksamitiene, E., Achanta, S., Kolch, W., Kholodenko, B. N., Hoek, J. B., Kiyatkin, A. (2011) 'Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells'. Cell Signal, 23 (11):1794-805. [Details]
Nguyen, L. K., Munoz-Garcia, J., Maccario, H., Ciechanover, A., Kolch, W., Kholodenko, B. N. (2011) 'Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System'. PLoS Comput Biol, 7 (12). [Details]
Aksamitiene, E,Achanta, S,Kolch, W,Kholodenko, BN,Hoek, JB,Kiyatkin, A; (2011) 'Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells'. Cellular Signalling, 23 :1794-1805. [DOI] [Details]
Sturm OE, Orton R, Grindlay J, Birtwistle M, Vyshemirsky V, Gilbert D, Calder M, Pitt A, Kholodenko B, Kolch W (2010) 'The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier'. Science signaling, 3 (153). [DOI] Link to full text [Details]
Aksamitiene, E., Kholodenko, B. N., Kolch, W., Hoek, J. B., Kiyatkin, A. (2010) 'PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells'. Cell Signal, 22 (9):1369-78. [Details]
Kholodenko, B. N., Hancock, J. F., Kolch, W. (2010) 'Signalling ballet in space and time'. Nat Rev Mol Cell Biol, 11 (6):414-26. [Details]
Sturm, O. E., Orton, R., Grindlay, J., Birtwistle, M., Vyshemirsky, V., Gilbert, D., Calder, M., Pitt, A., Kholodenko, B., Kolch, W. (2010) 'The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier'. Sci Signal, 3 (153). [Details]
Aksamitiene E, Kholodenko BN, Kolch W, Hoek JB, Kiyatkin A; (2010) 'PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells'. Cell, 22 (9):1369-1378. [DOI] Link to full text [Details]
Kholodenko BN, Hancock JF, Kolch W; (2010) 'Signalling ballet in space and time'. Nature reviews. Molecular cell biology, 11 (6):414-426. [DOI] Link to full text [Details]
Muñoz-García J, Kholodenko BN, Neufeld Z.; (2010) 'Formation of intracellular concentration landscapes by multisite protein modification'. Biophysical Journal, . [Details]
Nakakuki, T,Birtwistle, MR,Saeki, Y,Yumoto, N,Ide, K,Nagashima, T,Brusch, L,Ogunnaike, BA,Okada-Hatakeyama, M,Kholodenko, BN; (2010) 'Ligand-Specific c-Fos Expression Emerges from the Spatiotemporal Control of ErbB Network Dynamics'. Cell, 141 :884-896. [DOI] [Details]
Aksamitiene, E.Aksamitiene, E.,Kholodenko, B. N.Kholodenko, B. N.,Kolch, W.Kolch, W.,Hoek, J. B.Hoek, J. B.,Kiyatkin, A.Kiyatkin, A.; (2010) 'PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells'. Cell Signal, 22 (99):1369-781369. [Details]
Munoz-Garcia, J,Kholodenko, BN; (2010) 'Signalling over a distance: gradient patterns and phosphorylation waves within single cells'. Biochemical Society Transactions, 38 :1235-1241. [DOI] [Details]
Sturm, OE,Orton, R,Grindlay, J,Birtwistle, M,Vyshemirsky, V,Gilbert, D,Calder, M,Pitt, A,Kholodenko, B,Kolch, W; (2010) 'The Mammalian MAPK/ERK Pathway Exhibits Properties of a Negative Feedback Amplifier'. Science signaling, 3 . [DOI] [Details]
Muñoz-García J, Kholodenko BN, Neufeld Z (2010) 'Formation of intracellular concentration landscapes by multisite protein modification'. Biophysical Journal, 99 (1):59-66. [DOI] Link to full text [Details]
Muñoz-García J, Kholodenko BN (2010) 'Signalling over a distance: gradient patterns and phosphorylation waves within single cells'. Biochemical Society Transactions, 38 (5):1235-1241. [DOI] Link to full text [Details]
Muñoz-García J, Neufeld Z, Kholodenko BN (2009) 'Positional information generated by spatially distributed signaling cascades'. PLoS Computational Biology, 5 (3). [DOI] [Details]
Kholodenko BN; (2009) 'Spatially distributed cell signalling'. FEBS Letters, 583 (24):4006-4012. [DOI] Link to full text [Details]
Birtwistle MR, Kholodenko BN; (2009) 'Endocytosis and signalling: a meeting with mathematics'. Molecular Oncology, 3 (4):308-320. [DOI] Link to full text [Details]
Kholodenko BN, Birtwistle MR; (2009) 'Four-dimensional dynamics of MAPK information processing systems'. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 1 (1):28-44. [DOI] [Details]
Stelling J, Kholodenko BN; (2009) 'Signaling cascades as cellular devices for spatial computations'. Journal of Mathematical Biology, 58 (1-2):35-55. [DOI] [Details]
Kaimachnikov NP, Kholodenko BN; (2009) 'Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle'. FEBS Journal, 276 (15):4102-4118. [DOI] Link to full text [Details]
Suenaga A, Hatakeyama M, Kiyatkin AB, Radhakrishnan R, Taiji M, Kholodenko BN; (2009) 'Molecular dynamics simulations reveal that Tyr-317 phosphorylation reduces Shc binding affinity for phosphotyrosyl residues of epidermal growth factor receptor'. Biophysical Journal, 96 (6):2278-2288. [DOI] Link to full text [Details]
Borisov N, Aksamitiene E, Kiyatkin A, Legewie S, Berkhout J, Maiwald T, Kaimachnikov NP, Timmer J, Hoek JB, Kholodenko BN; (2009) 'Systems-level interactions between insulin-EGF networks amplify mitogenic signaling'. Molecular Systems Biology, 5 . [DOI] Link to full text [Details]
Suenaga, A,Hatakeyama, M,Kiyatkin, AB,Radhakrishnan, R,Taiji, M,Kholodenko, BN; (2009) 'Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor'. Biophysical Journal, 96 :2278-2288. [DOI] [Details]
Borisov, N,Aksamitiene, E,Kiyatkin, A,Legewie, S,Berkhout, J,Maiwald, T,Kaimachnikov, NP,Timmer, J,Hoek, JB,Kholodenko, BN; (2009) 'Systems-level interactions between insulin-EGF networks amplify mitogenic signaling'. Stem, 5 . [DOI] [Details]
Kaimachnikov, NP,Kholodenko, BN; (2009) 'Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle'. FEBS Journal, 276 :4102-4118. [DOI] [Details]
Munoz-Garcia, J,Neufeld, Z,Kholodenko, BN; (2009) 'Positional Information Generated by Spatially Distributed Signaling Cascades'. PLoS Computational Biology, 5 . [DOI] [Details]
Kaimachnikov, N. P.Kaimachnikov, N. P.,Kholodenko, B. N.Kholodenko, B. N.; (2009) 'Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle'. FEBS JFEBS JFEBS J, 276 (1515):4102-184102. Available Online [Details]
Suenaga, A.Suenaga, A.,Hatakeyama, M.Hatakeyama, M.,Kiyatkin, A. B.Kiyatkin, A. B.,Radhakrishnan, R.Radhakrishnan, R.,Taiji, M.Taiji, M.,Kholodenko, B. N.Kholodenko, B. N.; (2009) 'Molecular dynamics simulations reveal that Tyr-317 phosphorylation reduces Shc binding affinity for phosphotyrosyl residues of epidermal growth factor receptor'. Biophys JBiophys JBiophys J, 96 (66):2278-882278. Available Online [Details]
Munoz-Garcia, J.Munoz-Garcia, J.,Neufeld, Z.Neufeld, Z.,Kholodenko, B. N.Kholodenko, B. N.; (2009) 'Positional information generated by spatially distributed signaling cascades'. PLoS Comput BiolPLoS Comput BiolPLoS Comput Biol, 5 (33). Available Online [Details]
Munoz-Garcia, J., Neufeld, Z. and Kholodenko, B. ; (2009) 'Positional Information Generated by Spatially Distributed Signaling Cascades'. PLoS Computational Biology, 5 (3). [DOI] Link to full text [Details]
Kholodenko, B. N.Kholodenko, B. N.,Birtwistle, M. R.Birtwistle, M. R.; (2009) 'Four-dimensional dynamics of MAPK information processing systems'. Wiley Interdiscip Rev Syst Biol MedWiley Interdiscip Rev Syst Biol MedWiley Interdiscip Rev Syst Biol Med, 1 (11):28-4428. Available Online [Details]
Birtwistle, M. R.Birtwistle, M. R.,Kholodenko, B. N.Kholodenko, B. N.; (2009) 'Endocytosis and signalling: a meeting with mathematics'. Mol OncolMol OncolMol Oncol, 3 (44):308-20308. Available Online [Details]
Borisov, N.Borisov, N.,Aksamitiene, E.Aksamitiene, E.,Kiyatkin, A.Kiyatkin, A.,Legewie, S.Legewie, S.,Berkhout, J.Berkhout, J.,Maiwald, T.Maiwald, T.,Kaimachnikov, N. P.Kaimachnikov, N. P.,Timmer, J.Timmer, J.,Hoek, J. B.Hoek, J. B.,Kholodenko, B. N.Kholodenko, B. N.; (2009) 'Systems-level interactions between insulin-EGF networks amplify mitogenic signaling'. Mol Syst BiolMol Syst BiolMol Syst Biol, 5 :256256. Available Online [Details]
Borisov NM, Chistopolsky AS, Faeder JR, Kholodenko BN. (2008) 'Domain-oriented reduction of rule-based network models'. IET systems biology, . [Details]
Kholodenko, B. N., Kolch, W. (2008) 'Giving space to cell signaling'. Cell, 133 (4):566-567. [Details]
Borisov NM, Chistopolsky AS, Faeder JR, Kholodenko BN; (2008) 'Domain-oriented reduction of rule-based network models'. IET Systems Biology, 2 (5):342-351. [DOI] [Details]
Kholodenko BN, Sauro HM; (2008) 'Spatio-temporal dynamics of protein modification cascades'. Journal of Experimental Biology, 61 :141-159. [Details]
Kholodenko, B. N.Kholodenko, B. N.,Kolch, W.Kolch, W.; (2008) 'Giving space to cell signaling'. Cell, 133 (44):566-567566. [Details]
Aksamitiene E, Hoek JB, Kholodenko B, Kiyatkin A; (2007) 'Multistrip Western blotting to increase quantitative data output'. Electrophoresis, 28 (18):3163-3173. [DOI] [Details]
Kholodenko BN; (2007) 'Untangling the signalling wires'. Cell, 9 (3):247-249. [DOI] [Details]
Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN; (2007) 'Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses'. Molecular Systems Biology, 3 . [DOI] [Details]
Chickarmane V, Kholodenko BN, Sauro HM; (2007) 'Oscillatory dynamics arising from competitive inhibition and multisite phosphorylation'. Journal of Theoretical Biology, 244 (1):68-76. [DOI] [Details]
Ortega F, Garcés JL, Mas F, Kholodenko BN, Cascante M (2006) 'Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements'. FEBS Journal, 273 (17):3915-3926. [DOI] [Details]
Borisov NM, Markevich NI, Hoek JB, Kholodenko BN; (2006) 'Trading the micro-world of combinatorial complexity for the macro-world of protein interaction domains'. BioSystems, 83 (2-3):152-166. [DOI] [Details]
Markevich NI, Tsyganov MA, Hoek JB, Kholodenko BN; (2006) 'Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades'. Molecular Systems Biology, 2 . [DOI] [Details]
Conzelmann H, Saez-Rodriguez J, Sauter T, Kholodenko BN, Gilles ED; (2006) 'A domain-oriented approach to the reduction of combinatorial complexity in signal transduction networks'. BMC Bioinformatics, 7 . [DOI] [Details]
Kholodenko BN; (2006) 'Cell-signalling dynamics in time and space'. Nature Reviews Molecular Cell Biology, 7 (3):165-176. [DOI] [Details]
Yalamanchili N, Zak DE, Ogunnaike BA, Schwaber JS, Kriete A, Kholodenko BN; (2006) 'Quantifying gene network connectivity in silico: scalability and accuracy of a modular approach'. Systems Biology, 153 (4):236-246. [Details]
Kiyatkin A, Aksamitiene E, Markevich NI, Borisov NM, Hoek JB, Kholodenko BN; (2006) 'Scaffolding protein Grb2-associated binder 1 sustains epidermal growth factor-induced mitogenic and survival signaling by multiple positive feedback loops'. Journal of Biological Chemistry, 281 (29):19925-19938. [DOI] [Details]
Blüthgen N, Bruggeman FJ, Legewie S, Herzel H, Westerhoff HV, Kholodenko BN (2006) 'Effects of sequestration on signal transduction cascades'. FEBS Journal, 273 (5):895-906. [DOI] [Details]
Sakaki, Y.Sakaki, Y.,Kholodenko, B. N.Kholodenko, B. N.,Hatakeyama, M.Hatakeyama, M.,Kitano, H.Kitano, H.,Kolch, W.Kolch, W.,De, Meyts P.De, Meyts P.,Yarden, Y.Yarden, Y.,Westerhoff, H. V.Westerhoff, H. V.,Wiley, H. S.Wiley, H. S.; (2005) 'The International Consortium on Systems Biology of Receptor Tyrosine Kinase Regulatory Networks'. Syst.Biol.(Stevenage.), 152 (22):53-5453. [Details]
Sakaki, Y., Kholodenko, B. N., Hatakeyama, M., Kitano, H., Kolch, W., De, Meyts P., Yarden, Y., Westerhoff, H. V., Wiley, H. S. (2005) 'The International Consortium on Systems Biology of Receptor Tyrosine Kinase Regulatory Networks'. Syst.Biol.(Stevenage.), 152 (2):53-54. [Details]
Sakaki Y, Kholodenko BN, Hatakeyama M, Kitano H, Kolch W, De Meyts P, Yarden Y, Westerhoff HV, Wiley HS; (2005) 'The International Consortium on Systems Biology of Receptor Tyrosine Kinase Regulatory Networks'. Systems Biology, 152 (2):53-54. [Details]
Borisov NM, Markevich NI, Hoek JB, Kholodenko BN; (2005) 'Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexity'. Biophysical Journal, 89 (2):951-966. [DOI] [Details]
Andrec M, Kholodenko BN, Levy RM, Sontag E; (2005) 'Inference of signaling and gene regulatory networks by steady-state perturbation experiments: structure and accuracy'. Journal of Theoretical Biology, 232 (3):427-441. [DOI] [Details]
Sontag E, Kiyatkin A, Kholodenko BN; (2004) 'Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data'. Bioinformatics, 20 (12):1877-1886. [DOI] [Details]
Markevich NI, Moehren G, Demin OV, Kiyatkin A, Hoek JB, Kholodenko BN; (2004) 'Signal processing at the Ras circuit: what shapes Ras activation patterns?'. Systems Biology, 1 (1):104-113. [Details]
Sauro HM, Kholodenko BN; (2004) 'Quantitative analysis of signaling networks'. Progress in Biophysics and Molecular Biology, 86 (1):5-43. [DOI] [Details]
Markevich NI, Hoek JB, Kholodenko BN; (2004) 'Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades'. Cell, 164 (3):353-359. [DOI] [Details]
Suenaga A, Kiyatkin AB, Hatakeyama M, Futatsugi N, Okimoto N, Hirano Y, Narumi T, Kawai A, Susukita R, Koishi T, Furusawa H, Yasuoka K, Takada N, Ohno Y, Taiji M, Ebisuzaki T, Hoek JB, Konagaya A, Kholodenko BN; (2004) 'Tyr-317 phosphorylation increases Shc structural rigidity and reduces coupling of domain motions remote from the phosphorylation site as revealed by molecular dynamics simulations'. Journal of Biological Chemistry, 279 (6):4657-4662. [DOI] [Details]
Peletier MA, Westerhoff HV, Kholodenko BN; (2003) 'Control of spatially heterogeneous and time-varying cellular reaction networks: a new summation law'. Journal of Theoretical Biology, 225 (4):477-487. [Details]
Kholodenko BN; (2003) 'Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors'. Journal of Experimental Biology, 206 (Pt 12):2073-2082. [Details]
Reijenga KA, Westerhoff HV, Kholodenko BN, Snoep JL; (2002) 'Control analysis for autonomously oscillating biochemical networks'. Biophysical Journal, 82 (1 Pt 1):99-108. [DOI] [Details]
Bruggeman FJ, Kholodenko BN; (2002) 'Modular interaction strengths in regulatory networks; an example'. Molecular Biology Reports, 29 (1-2):57-61. [Details]
Kholodenko BN; (2002) 'MAP kinase cascade signaling and endocytic trafficking: a marriage of convenience?'. Cell, 12 (4):173-177. [Details]
Bruggeman FJ, Westerhoff HV, Hoek JB, Kholodenko BN; (2002) 'Modular response analysis of cellular regulatory networks'. Journal of Theoretical Biology, 218 (4):507-520. [Details]
Moehren G, Markevich N, Demin O, Kiyatkin A, Goryanin I, Hoek JB, Kholodenko BN; (2002) 'Temperature dependence of the epidermal growth factor receptor signaling network can be accounted for by a kinetic model'. Journal of Biochemistry, 41 (1):306-320. [Details]
Kholodenko BN, Kiyatkin A, Bruggeman FJ, Sontag E, Westerhoff HV, Hoek JB; (2002) 'Untangling the wires: a strategy to trace functional interactions in signaling and gene networks'. Proceedings of the National Academy of Sciences of the United States of America, 99 (20):12841-12846. [DOI] [Details]
De Atauri P, Acerenza L, Kholodenko BN, De La Iglesia N, Guinovart JJ, Agius L, Cascante M; (2001) 'Occurrence of paradoxical or sustained control by an enzyme when overexpressed: necessary conditions and experimental evidence with regard to hepatic glucokinase'. Biochemical Journal, 355 (Pt 3):787-793. [Details]
Demin OV, Gorianin II, Kholodenko BN, Westerhoff HV; (2001) '[Kinetic modeling of energy metabolism and generation of active forms of oxygen in hepatocyte mitochondria]'. Molekuliarnaia biologiia, 35 (6):1095-1104. [Details]
Marcinkeviciute A, Mildaziene V, Crumm S, Demin O, Hoek JB, Kholodenko B; (2000) 'Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding'. Biochemical Journal, 349 (Pt 2):519-526. [Details]
Kholodenko BN, Westerhoff HV, Schwaber J, Cascante M; (2000) 'Engineering a living cell to desired metabolite concentrations and fluxes: pathways with multifunctional enzymes'. Metabolic Engineering, 2 (1):1-13. [DOI] [Details]
Kholodenko BN; (2000) 'Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades'. European journal of biochemistry / FEBS, 267 (6):1583-1588. [Details]
Schuster S, Kholodenko BN, Westerhoff HV; (2000) 'Cellular information transfer regarded from a stoichiometry and control analysis perspective'. BioSystems, 55 (1-3):73-81. [Details]
Kholodenko BN, Brown GC, Hoek JB; (2000) 'Diffusion control of protein phosphorylation in signal transduction pathways'. Biochemical Journal, 350 Pt 3 :901-907. [Details]
Kholodenko BN, Hoek JB, Westerhoff HV; (2000) 'Why cytoplasmic signalling proteins should be recruited to cell membranes'. Cell, 10 (5):173-178. [Details]
van Heeswijk WC, Bakker BM, Teusink B, Kholodenko BN, Somsen OJ, Snoep JL, Westerhoff HV; (1999) 'Live control of the living cell'. Biochemical Society Transactions, 27 (2):261-264. [Details]
Kholodenko BN, Demin OV, Moehren G, Hoek JB; (1999) 'Quantification of short term signaling by the epidermal growth factor receptor'. Journal of Biological Chemistry, 274 (42):30169-30181. [Details]
Brown GC, Kholodenko BN; (1999) 'Spatial gradients of cellular phospho-proteins'. FEBS Letters, 457 (3):452-454. [Details]
Hoek JB, Kholodenko BN; (1998) 'The intracellular signaling network as a target for ethanol'. Alcoholism: Clinical and Experimental Research, 22 (5 Suppl):1-1. [Details]
Rohwer JM, Postma PW, Kholodenko BN, Westerhoff HV; (1998) 'Implications of macromolecular crowding for signal transduction and metabolite channeling'. Proceedings of the National Academy of Sciences of the United States of America, 95 (18):10547-10552. [Details]
Demin OV, Westerhoff HV, Kholodenko BN; (1998) 'Mathematical modelling of superoxide generation with the bc1 complex of mitochondria'. Journal of Biochemistry, 63 (6):634-649. [Details]
Kholodenko BN, Schuster S, Garcia J, Westerhoff HV, Cascante M; (1998) 'Control analysis of metabolic systems involving quasi-equilibrium reactions'. Biochimica et biophysica acta, 1379 (3):337-352. [Details]
Kholodenko BN, Rohwer JM, Cascante M, Westerhoff HV; (1998) 'Subtleties in control by metabolic channelling and enzyme organization'. Cell, 184 (1-2):311-320. [Details]
Kholodenko BN, Cascante M, Hoek JB, Westerhoff HV, Schwaber J; (1998) 'Metabolic design: how to engineer a living cell to desired metabolite concentrations and fluxes'. Biotechnology and Bioengineering, 59 (2):239-247. [Details]
Demin OV, Kholodenko BN, Skulachev VP; (1998) 'A model of O2.-generation in the complex III of the electron transport chain'. Cell, 184 (1-2):21-33. [Details]
Kholodenko BN, Brown GC, Hoek JB; (1997) 'Why do protein kinase cascades have more than one level?'. Trends in Biochemical Sciences, 22 (8). [Details]
Kholodenko BN, Hoek JB, Westerhoff HV, Brown GC; (1997) 'Quantification of information transfer via cellular signal transduction pathways'. FEBS Letters, 414 (2):430-434. [Details]
Brown GC, Westerhoff HV, Kholodenko BN; (1996) 'Molecular control analysis: control within proteins and molecular processes'. Journal of Theoretical Biology, 182 (3):389-396. [DOI] [Details]
Nartsissov IaR, Kholodenko BN; (1996) '[Control of the rate of the glucokinase reaction by its elementary stages]'. Biokhimiia (Moscow, Russia), 61 (7):1279-1284. [Details]
Kholodenko BN, Sakamoto N, Puigjaner J, Westerhoff HV, Cascante M; (1996) 'Strong control on the transit time in metabolic channelling'. FEBS Letters, 389 (2):123-125. [Details]
Mildaziene V, Baniene R, Nauciene Z, Marcinkeviciute A, Morkuniene R, Borutaite V, Kholodenko B, Brown GC; (1996) 'Ca2+ stimulates both the respiratory and phosphorylation subsystems in rat heart mitochondria'. Biochemical Journal, 320 ( Pt 1) :329-334. [Details]
Kholodenko BN, Brown GC; (1996) 'Paradoxical control properties of enzymes within pathways: can activation cause an enzyme to have increased control?'. Biochemical Journal, 314 ( Pt 3) :753-760. [Details]
Kholodenko BN, Westerhoff HV, Cascante M; (1996) 'Effect of channelling on the concentration of bulk-phase intermediates as cytosolic proteins become more concentrated'. Biochemical Journal, 313 ( Pt 3) :921-926. [Details]
Bier M, Teusink B, Kholodenko BN, Westerhoff HV; (1996) 'Control analysis of glycolytic oscillations'. Biophysical Chemistry, 62 (1-3):15-24. [Details]
Cascante M, Meléndez-Hevia E, Kholodenko B, Sicilia J, Kacser H (1995) 'Control analysis of transit time for free and enzyme-bound metabolites: physiological and evolutionary significance of metabolic response times'. Biochemical Journal, 308 ( Pt 3) :895-899. [Details]
Kholodenko BN, Schuster S, Rohwer JM, Cascante M, Westerhoff HV; (1995) 'Composite control of cell function: metabolic pathways behaving as single control units'. FEBS Letters, 368 (1):1-4. [Details]
Kholodenko BN, Westerhoff HV, Puigjaner J, Cascante M; (1995) 'Control in channelled pathways. A matrix method calculating the enzyme control coefficients'. Biophysical Chemistry, 53 (3):247-258. [Details]
Kholodenko BN, Cascante M, Westerhoff HV; (1995) 'Control theory of metabolic channelling'. Cell, 143 (2):151-168. [Details]
Kholodenko BN, Molenaar D, Schuster S, Heinrich R, Westerhoff HV; (1995) 'Defining control coefficients in non-ideal metabolic pathways'. Biophysical Chemistry, 56 (3):215-226. [Details]
Mildaziene V, Baniene R, Nauciene Z, Bakker BM, Brown GC, Westerhoff HV, Kholodenko BN; (1995) 'Calcium indirectly increases the control exerted by the adenine nucleotide translocator over 2-oxoglutarate oxidation in rat heart mitochondria'. Archives of Biochemistry and Biophysics, 324 (1):130-134. [DOI] [Details]
Kholodenko BN, Westerhoff HV; (1995) 'The macroworld versus the microworld of biochemical regulation and control'. Trends in Biochemical Sciences, 20 (2):52-54. [Details]
Kholodenko BN, Sauro HM, Westerhoff HV, Cascante M; (1995) 'Coenzyme cycles and metabolic control analysis: the determination of the elasticity coefficients from the generalised connectivity theorem'. Biochemistry and Molecular Biology International, 35 (3):615-625. [Details]
Jensen PR, Snoep JL, Molenaar D, van Heeswijk WC, Kholodenko BN, van der Gugten AA, Westerhoff HV; (1995) 'Molecular biology for flux control'. Biochemical Society Transactions, 23 (2):367-370. [Details]
Westerhoff HV, Kholodenko BN, Cascante M, Van Dam K; (1995) 'Elusive control'. Journal of Bioenergetics and Biomembranes, 27 (5):491-497. [Details]
Kholodenko BN, Sauro HM, Westerhoff HV; (1994) 'Control by enzymes, coenzymes and conserved moieties. A generalisation of the connectivity theorem of metabolic control analysis'. European journal of biochemistry / FEBS, 225 (1):179-186. [Details]
Westerhoff HV, Hofmeyr JH, Kholodenko BN; (1994) 'Getting to the inside of cells using metabolic control analysis'. Biophysical Chemistry, 50 (3):273-283. [Details]
Kholodenko BN, Westerhoff HV, Brown GC; (1994) 'Rate limitation within a single enzyme is directly related to enzyme intermediate levels'. FEBS Letters, 349 (1):131-134. [Details]
Kholodenko BN, Cascante M, Westerhoff HV; (1994) 'Control theory of metabolic channelling'. Cell, 133-134 :313-331. [Details]
Snoep JL, Jensen PR, Groeneveld P, Molenaar D, Kholodenko BN, Westerhoff HV; (1994) 'How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox'. Biochemistry and Molecular Biology International, 33 (5):1023-1032. [Details]
Kholodenko BN, Westerhoff HV; (1994) 'Control theory of one enzyme'. Biochimica et biophysica acta, 1208 (2):294-305. [Details]
Kholodenko BN. (1993) 'Kinetic models of coupling between H+ and Na(+)-translocation and ATP synthesis/hydrolysis by F0F1-ATPases: can a cell utilize both delta mu H+ and delta mu Na+ for ATP synthesis under in vivo conditions using the same enzyme?'. Journal of bioenergetics and biomembranes, . [Details]
Borutaité V, Mildaziene V, Katiliuté Z, Kholodenko B, Toleikis A (1993) 'The function of ATP/ADP translocator in the regulation of mitochondrial respiration during development of heart ischemic injury'. Biochimica et biophysica acta, 1142 (1-2):175-180. [Details]
Kholodenko BN, Demin OV, Westerhoff HV; (1993) ''Channelled' pathways can be more sensitive to specific regulatory signals'. FEBS Letters, 320 (1):75-78. [Details]
van Dam K, van der Vlag J, Kholodenko BN, Westerhoff HV; (1993) 'The sum of the control coefficients of all enzymes on the flux through a group-transfer pathway can be as high as two'. European journal of biochemistry / FEBS, 212 (3):791-799. [Details]
Kholodenko BN; (1993) 'Kinetic models of coupling between H+ and Na(+)-translocation and ATP synthesis/hydrolysis by F0F1-ATPases: can a cell utilize both delta mu H+ and delta mu Na+ for ATP synthesis under in vivo conditions using the same enzyme?'. Journal of Bioenergetics and Biomembranes, 25 (3):285-295. [Details]
Kholodenko BN, Cascante M, Westerhoff HV; (1993) 'Dramatic changes in control properties that accompany channelling and metabolite sequestration'. FEBS Letters, 336 (3):381-384. [Details]
Kholodenko BN, Westerhoff HV; (1993) 'Metabolic channelling and control of the flux'. FEBS Letters, 320 (1):71-74. [Details]
Borutaité V, Mildaziene V, Katiliuté Z, Kholodenko B, Toleikis A. (1993) 'The function of ATP/ADP translocator in the regulation of mitochondrial respiration during development of heart ischemic injury'. Biochima Et Biophysica Acta - Molecular Cell Research, . [Details]
Kholodenko BN, Lyubarev AE, Kurganov BI; (1992) 'Control of the metabolic flux in a system with high enzyme concentrations and moiety-conserved cycles. The sum of the flux control coefficients can drop significantly below unity'. European journal of biochemistry / FEBS, 210 (1):147-153. [Details]
Kholodenko BN, Millazhane VIu, BorutaÄ­te VI, Ivanovene LI, IuodkaÄ­te RA, Katiliute ZP, ToleÄ­kis AN (1991) '[Regulation of the heart mitochondrial respiration rate. Comparison of oxidation of succinate and NAD-dependent substrates]'. Biokhimiia (Moscow, Russia), 56 (8):1420-1428. [Details]
Kholodenko BN, Erlikh LI; (1989) '[Theory of metabolism regulation: a complete system of equations for regulation coefficients]'. Biofizika, 34 (5):802-807. [Details]
Borutaite V, Mildaziene V, Ivanoviene L, Kholodenko B, Toleikis A, Praskevicius A; (1989) 'The role of long-chain acyl-CoA in the damage of oxidative phosphorylation in heart mitochondria'. FEBS Letters, 243 (2):264-266. [Details]
Kholodenko BN; (1988) 'How do external parameters control fluxes and concentrations of metabolites? An additional relationship in the theory of metabolic control'. FEBS Letters, 232 (2):383-386. [Details]
Kholodenko BN; (1988) '[A new theorem in the theory of metabolism regulation: how external parameters control the flow and concentration of metabolites]'. Biofizika, 33 (1):145-147. [Details]
Kholodenko BN; (1988) '[Control of molecular transformations in polyenzyme systems: quantitative theory of the regulation of metabolism]'. Molekuliarnaia biologiia, 22 (5):1238-1256. [Details]
Kholodenko B, Zilinskiene V, Borutaite V, Ivanoviene L, Toleikis A, Praskevicius A; (1987) 'The role of adenine nucleotide translocators in regulation of oxidative phosphorylation in heart mitochondria'. FEBS Letters, 223 (2):247-250. [Details]
Kholodenko BN; (1987) '[Degree of stability of metabolic chain with 1 feedback loop]'. Biofizika, 32 (3):424-428. [Details]
Kholodenko BN, Stepanchikova AV, Erlikh LI, Ataullakhanov FI, ZhabotinskiÄ­ AM (1985) '[Role of the 2,3-diphosphoglycerate shunt in regulating energy metabolism in human erythrocytes]'. Izvestiia Akademii nauk SSSR. Seriia biologicheskaia, (2):196-205. [Details]
Kholodenko BN. (1984) 'The mitochondrial carrier of adenylates controls ATP production in the physiological range of respiration rates]'. Biofizika, . [Details]
Kholodenko BN; (1984) 'Control of mitochondrial oxidative phosphorylation'. Journal of Theoretical Biology, 107 (2):179-188. [Details]
Kholodenko BN; (1984) '[The mitochondrial carrier of adenylates controls ATP production in the physiological range of respiration rates]'. Biofizika, 29 (3):453-458. [Details]
Kholodenko BN; (1983) '[Power-law approximation and similarity properties of metabolic regulatory characteristics]'. Biofizika, 28 (4):674-681. [Details]
Kholodenko BN, Geviksman KhV, Kholodov LE; (1982) '[Optical tactics of antibacterial therapy for the trigger model of the infection process]'. Biofizika, 27 (5):900-905. [Details]
Dibrov BF, Zhabotinsky AM, Kholodenko BN; (1982) 'Dynamic stability of steady states and static stabilization in unbranched metabolic pathways'. Journal of Mathematical Biology, 15 (1):51-63. [Details]
Dibrov BF, ZhabotinskiÄ­ AM, Kholodenko BN (1981) '[Dynamic stability and parametric stabilization of steady states of unbranched metabolic pathways]'. Biofizika, 26 (5):790-795. [Details]
Ataullakhanov FI, Vitvitsky VM, Zhabotinsky AM, Pichugin AV, Platonova OV, Kholodenko BN, Ehrlich LI; (1981) 'The regulation of glycolysis in human erythrocytes. The dependence of the glycolytic flux on the ATP concentration'. European journal of biochemistry / FEBS, 115 (2):359-365. [Details]
Ataullakhanov FI, Vitvitsky VM, Zhabotinsky AM, Pichugin AV, Kholodenko BN, Ehrlich LI; (1981) 'Regulation of glycolysis in human erythrocytes. The mechanism of ATP concentration stabilization'. Acta Biologica et Medica Germanica, 40 (7-8):991-997. [Details]
Dibrov BF, ZhabotinskiÄ­ AM, Kholodenko BN (1981) '[Dynamic stability of a metabolic pathway with single-loop feedback]'. Biofizika, 26 (4):590-595. [Details]
Kholodenko BN, Dibrov BF, ZhabotinskiÄ­ AM (1981) '[Regulation of erythrocyte energy metabolism. Dependence of glycolysis characteristics on donor individual parameters]'. Biofizika, 26 (3):501-506. [Details]
Kholodenko BN; (1980) '[Stabilization of the relative concentration of ATP and invariants in the regulation of erythrocyte energy metabolism]'. Biofizika, 25 (2):258-264. [Details]
Kholodenko BN; (1980) '[Biochemical individuality of humans and invariants of regulation. Scale invariance of the characteristic of glycolysis in erythrocytes]'. Biofizika, 25 (2):250-257. [Details]
Ataullakhanov FI, VitvitskiÄ­ VM, ZhabotinskiÄ­ AM, Pichugin AV, Kholodenko BN (1979) '[Quantitative model of human erythrocyte glycolysis. Region of cell viability determined by ATP concentration]'. Biofizika, 24 (6):1048-1053. [Details]
Kholodenko BN; (1979) '[Study of the dynamic behavior of the glycolytic system using the simplest model]'. Biofizika, 24 (4):640-645. [Details]
Kholodenko BN; (1974) '[Nets of excitable elements. VII. Stabilization of the excitation level by inhibiting bonds]'. Biofizika, 19 (4):722-727. [Details]
Kholodenko BN; (1974) '[Nets of excitable elements. IV. Nets of elements without refractoriness in continuous time]'. Biofizika, 19 (2):324-329. [Details]
Kholodenko BN, Chetaev AN; (1973) '[Nets of excitable elements. 3. Ring-type nets]'. Biofizika, 18 (2):361-364. [Details]
Kholodenko BN; (1972) '[Correlation of impulse currents for a neuron model with multiple inputs]'. Biofizika, 17 (1):175-177. [Details]
 

Conference Publications

Kuehn, A; Kholodenko BN; Fey, D (2014) A dynamic model of the MYCN regulated DNA damage response in Neuroblastoma IEEE International Conference on Bioinformatics and Biomedicine (BIBM 2014) Workshop ¿Empowering Systems Medicine through optimal design of experimentation and computational modeling¿, Belfast Belfast, , 02-NOV-14 - 05-DEC-14 , pp.S3203 Link to full text [Details]
Dobrzyński, M; Fey, D; Nguyen, LK; Kholodenko, BN (2012) Bimodal Protein Distributions in Heterogeneous Oscillating Systems . In: Gilbert, David and Heiner, Monika eds. 10th International Conference, CMSB 2012, London, UK Available Online [Details]
Dobrzynski, M; Fey, D; Nguyen, LK; Kholodenko, BN (2012) Bimodal Protein Distributions in Heterogeneous Oscillating Systems Proceedings of the 10th International Conference on Computational Methods in Systems Biology (CMSB), London, UK , pp.17-28 Available Online [Details]
Kholodenko, BN (2009) FEBS LETTERS Spatially distributed cell signalling , pp.4006-4012 [DOI] [Details]
                       

Abstract

Kolch, W,Birtwistle, M,Kholodenko, B,Grindlay, J,Sturm, O,Orton, R,Gilbert, D,von Kriegsheim, A (2010) From benchside to byteside: what we can learn from computational modelling. Abstract [Details]
       

Reviews

Nguyen, LK,Matallanas, D,Croucher, DR,von Kriegsheim, A,Kholodenko, BN (2013) Signalling by protein phosphatases and drug development: a systems-centred view. Reviews [DOI] [Details]
Baljuls, A,Kholodenko, BN,Kolch, W (2013) It takes two to tango - signalling by dimeric Raf kinases. Reviews [DOI] [Details]
Kholodenko, B,Yaffe, MB,Kolch, W (2012) Computational Approaches for Analyzing Information Flow in Biological Networks. Reviews [DOI] [Details]
Kholodenko, BN,Hancock, JF,Kolch, W (2010) Signalling ballet in space and time. Reviews [DOI] [Details]
Birtwistle, MR,Kholodenko, BN (2009) Endocytosis and signalling: A meeting with mathematics. Reviews [DOI] [Details]
                                         

Published abstracts

Kolch W, Fey D, Halasz M, Rauch N, Munoz AG, Pilkington R, Kholodenko BN, Croucher DR, Kennedy SP, Hastings JF, Westermann F, Dreidax D, Fischer M, Duffy D, Krstic A, Schwarzl T. (2015) Personalized cancer diagnostics and therapeutics based on the computational modelling of signal transduction networks. Published abstracts [Details]
Halasz, M; Santra, T; Rodriguez, J; Kholodenko, B; Kolch W (2014) Proteomic profiling of N-Myc-associated proteins in neuroblastoma. Published abstracts [Details]
           

Comment

Bastiaens P, Birtwistle MR;Bl¿¿thgen N;Bruggeman FJ;Cho KH;Cosentino C;de la Fuente A;Hoek JB;Kiyatkin A;Klamt S;Kolch W;Legewie S;Mendes P;Naka T;Santra T;Sontag E;Westerhoff HV;Kholodenko BN (2015) Silence on the relevant literature and errors in implementation. Comment [DOI] [Details]
                   

Research

Research Interests

Research Projects

Sponsor : University College Dublin (UCD)
Title : Guanine Nucleotide Inhibitor binding governs the protrusion-retraction process in migrating cells.
Start Date / End Date : 01-MAY-13 / 31-OCT-14
Sponsor : EC Framework (FP7)
Title : Synthetic Cellular Signaling Circuits (SynSignal)
Start Date / End Date : 01-NOV-13 / 31-OCT-17
Sponsor : Science Foundation Ireland (SFI)
Title : Stokes Professorship
Start Date / End Date : 31-JAN-09 / 30-JAN-14
Sponsor : Higher Education Authority (HEA)
Title : PRTLI 5: SimSci - Split Accounts School of Mathematical Sciences
Start Date / End Date : 01-MAR-11 / 31-DEC-16
Sponsor : Science Foundation Ireland (SFI)
Title : Walton Fellowship: Dynamic rewiring of Rho family GTPase signalling fluxes in cancer cell invasion
Start Date / End Date : 01-MAR-12 / 31-AUG-12
Sponsor : AstraZeneca UK Ltd.
Title : CRC50: Modelling synergistic combinations
Start Date / End Date : 13-NOV-09 / 31-MAY-12
Sponsor : RIKEN
Title : Modeling and Experimental Studies of Cellular Signal Transduction Networks
Start Date / End Date : 01-JUN-09 / 31-MAR-19