Douglas Lauffenburger

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. pmc Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli
    Melody K Morris
    Center for Cell Decision Processes, Massachusetts Institute of Technology and Harvard Medical School, Boston, MA, USA
    PLoS Comput Biol 7:e1001099. 2011
  2. pmc Cancer systems biology: a network modeling perspective
    Pamela K Kreeger
    Department of Biomedical Engineering, University of Wisconsin Madison, Madison, WI 53706, USA
    Carcinogenesis 31:2-8. 2010
  3. pmc Logic-based models for the analysis of cell signaling networks
    Melody K Morris
    Center for Cell Decision Process and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 49:3216-24. 2010
  4. pmc Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs modulate human microvascular endothelial signaling in a three-dimensional matrix migration context
    Ta chun Hang
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Mol Cell Proteomics 12:3704-18. 2013
  5. pmc MCAM: multiple clustering analysis methodology for deriving hypotheses and insights from high-throughput proteomic datasets
    Kristen M Naegle
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Comput Biol 7:e1002119. 2011
  6. pmc Signaling network state predicts twist-mediated effects on breast cell migration across diverse growth factor contexts
    Hyung Do Kim
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA
    Mol Cell Proteomics 10:M111.008433. 2011
  7. pmc Fuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/insulin-induced signaling
    Bree B Aldridge
    Center for Cell Decision Processes, Cambridge, Massachusetts, United States of America
    PLoS Comput Biol 5:e1000340. 2009
  8. pmc 2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen
    Aaron S Meyer
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 197:721-9. 2012
  9. pmc Normalization and statistical analysis of multiplexed bead-based immunoassay data using mixed-effects modeling
    David C Clarke
    Department of Biological Engineering and Center for Cellular Decision Processes, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell Proteomics 12:245-62. 2013
  10. pmc Autocrine epidermal growth factor signaling stimulates directionally persistent mammary epithelial cell migration
    G Maheshwari
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 155:1123-8. 2001

Research Grants

  1. Computational Modeling of Cell Migration in 3D Matrices
    Douglas Lauffenburger; Fiscal Year: 2009
  2. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2004
  3. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2003
  4. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2002
  5. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2002
  6. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2002
  7. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2001
  8. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2001
  9. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2000
  10. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 1999

Collaborators

Detail Information

Publications107 found, 100 shown here

  1. pmc Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli
    Melody K Morris
    Center for Cell Decision Processes, Massachusetts Institute of Technology and Harvard Medical School, Boston, MA, USA
    PLoS Comput Biol 7:e1001099. 2011
    ..This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone...
  2. pmc Cancer systems biology: a network modeling perspective
    Pamela K Kreeger
    Department of Biomedical Engineering, University of Wisconsin Madison, Madison, WI 53706, USA
    Carcinogenesis 31:2-8. 2010
    ....
  3. pmc Logic-based models for the analysis of cell signaling networks
    Melody K Morris
    Center for Cell Decision Process and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 49:3216-24. 2010
    ....
  4. pmc Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs modulate human microvascular endothelial signaling in a three-dimensional matrix migration context
    Ta chun Hang
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Mol Cell Proteomics 12:3704-18. 2013
    ....
  5. pmc MCAM: multiple clustering analysis methodology for deriving hypotheses and insights from high-throughput proteomic datasets
    Kristen M Naegle
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Comput Biol 7:e1002119. 2011
    ..Overall, we offer MCAM as a broadly-applicable approach for analysis of proteomic data which may help increase the current understanding of molecular networks in a variety of biological problems...
  6. pmc Signaling network state predicts twist-mediated effects on breast cell migration across diverse growth factor contexts
    Hyung Do Kim
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA
    Mol Cell Proteomics 10:M111.008433. 2011
    ....
  7. pmc Fuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/insulin-induced signaling
    Bree B Aldridge
    Center for Cell Decision Processes, Cambridge, Massachusetts, United States of America
    PLoS Comput Biol 5:e1000340. 2009
    ..More generally, fuzzy logic models are flexible, able to incorporate qualitative and noisy data, and powerful enough to produce quantitative predictions and new biological insights about the operation of signaling networks...
  8. pmc 2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen
    Aaron S Meyer
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 197:721-9. 2012
    ..Interestingly, we observed this to be a more reliable relationship than cognate receptor expression or activation levels across these and two additional mammary tumor lines...
  9. pmc Normalization and statistical analysis of multiplexed bead-based immunoassay data using mixed-effects modeling
    David C Clarke
    Department of Biological Engineering and Center for Cellular Decision Processes, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell Proteomics 12:245-62. 2013
    ....
  10. pmc Autocrine epidermal growth factor signaling stimulates directionally persistent mammary epithelial cell migration
    G Maheshwari
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 155:1123-8. 2001
    ..These findings emphasize the functional importance of spatial restriction of EGFR signaling, and suggest critical implications for growth factor-based therapeutic treatments...
  11. pmc Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of naïve CD8(+) T cells
    Megan J Palmer
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Immunol Cell Biol 89:581-94. 2011
    ..Our findings indicate that IL-7R-mediated signaling not only maintains the size but also impacts the diversity of the naïve T-cell repertoire...
  12. pmc CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms
    Camille Terfve
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
    BMC Syst Biol 6:133. 2012
    ..Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce...
  13. pmc Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks
    Daniel C Kirouac
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    BMC Syst Biol 6:29. 2012
    ..We sought to determine whether these databases contain overlapping information and whether they can be used to construct high reliability prior knowledge networks for subsequent modeling of experimental data...
  14. pmc Endothelial cell phenotypic behaviors cluster into dynamic state transition programs modulated by angiogenic and angiostatic cytokines
    Tharathorn Rimchala
    Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA
    Integr Biol (Camb) 5:510-22. 2013
    ..Migratory cluster weights show only mild association with sprout density outcomes under the VEGF/PF4 conditions and the sprout formation characteristics explored here...
  15. pmc Decision tree modeling predicts effects of inhibiting contractility signaling on cell motility
    Sourabh Kharait
    Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    BMC Syst Biol 1:9. 2007
    ....
  16. pmc Transforming Boolean models to continuous models: methodology and application to T-cell receptor signaling
    Dominik M Wittmann
    Institute for Bioinformatics and Systems Biology, Helmholtz Zentrum Munchen German Research Center for Environmental Health, Neuherberg, Germany
    BMC Syst Biol 3:98. 2009
    ..Nowadays however, experiments yield more and more quantitative data. An obvious question therefore is how qualitative models can be used to explain and predict the outcome of these experiments...
  17. doi request reprint ROCK in a stiff place
    Douglas A Lauffenburger
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Sci Transl Med 3:112fs12. 2011
    ..this issue)...
  18. pmc Quantitative parsing of cell multi-tasking in wound repair and tissue morphogenesis
    Douglas A Lauffenburger
    Biological Engineering Division, Biology Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biophys J 84:3499-500. 2003
  19. ncbi request reprint Scratching the (cell) surface: cytokine engineering for improved ligand/receptor trafficking dynamics
    D A Lauffenburger
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA
    Chem Biol 5:R257-63. 1998
    ..By combining protein-engineering techniques with studies of receptor trafficking and signaling, it might be possible to identify the ligand receptor-binding properties that should be sought...
  20. pmc Real-time quantitative measurement of autocrine ligand binding indicates that autocrine loops are spatially localized
    D A Lauffenburger
    Division of Bioengineering and Environmental Health and Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 95:15368-73. 1998
    ..This result indicates that autocrine-based signals can operate in a spatially restricted, local manner and thus provide cells with information on their local microenvironment...
  21. ncbi request reprint Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis: distribution of homo- and heterodimers depends on relative HER2 levels
    Bart S Hendriks
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 278:23343-51. 2003
    ....
  22. pmc HER2-mediated effects on EGFR endosomal sorting: analysis of biophysical mechanisms
    Bart S Hendriks
    Department of Chemical Engineering, Biological Engineering Division, and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biophys J 85:2732-45. 2003
    ..In contrast, model predictions for alternative mechanisms-blocking of EGFR/ERC coupling, or altering EGF/EGFR dissociation-were inconsistent with the qualitative trends of the experimental data...
  23. pmc Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling
    Jamie B Spangler
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 107:13252-7. 2010
    ..These new insights will aid in ongoing rational design of EGFR-targeted antibody therapeutics...
  24. ncbi request reprint Epidermal growth factor induces acute matrix contraction and subsequent calpain-modulated relaxation
    Fred D Allen
    Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Wound Repair Regen 10:67-76. 2002
    ..Countervailing processes that down-regulate calpain activation can, accordingly, direct the transition of cell function from locomotion to matrix contraction...
  25. pmc Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells
    Manu O Platt
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    J Cell Physiol 221:306-17. 2009
    ..Taken together, our results show that enhanced MSC osteogenic differentiation corresponds to a sustained combination of receptor expression and ligand presentation, both of which are maintained by tEGF...
  26. ncbi request reprint A compendium of signals and responses triggered by prodeath and prosurvival cytokines
    Suzanne Gaudet
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell Proteomics 4:1569-90. 2005
    ..We conclude that it is possible to build self-consistent compendia of cell-signaling data that can be mined computationally to yield important insights into the control of mammalian cell responses...
  27. pmc Effects of HER2 overexpression on cell signaling networks governing proliferation and migration
    Alejandro Wolf-Yadlin
    Biological Engineering Division, MIT, Cambridge, MA, USA
    Mol Syst Biol 2:54. 2006
    ..Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration...
  28. pmc Proteolytic Activity Matrix Analysis (PrAMA) for simultaneous determination of multiple protease activities
    Miles A Miller
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Integr Biol (Camb) 3:422-38. 2011
    ..Moreover, our approach may extend to other families of proteases, such as caspases and cathepsins, that also can lack highly-specific substrates...
  29. pmc Mena binds α5 integrin directly and modulates α5β1 function
    Stephanie L Gupton
    The David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Biol 198:657-76. 2012
    ..Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins...
  30. ncbi request reprint Building with a scaffold: emerging strategies for high- to low-level cellular modeling
    Trey Ideker
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Trends Biotechnol 21:255-62. 2003
    ..Large-scale experimental measurements validate high-level models, whereas targeted experimental manipulations and measurements test low-level models...
  31. pmc BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner
    Ken S Lau
    Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 7:e41343. 2012
    ..Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value...
  32. pmc Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity
    Miles Miller
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS Comput Biol 8:e1002579. 2012
    ....
  33. ncbi request reprint A biological approach to computational models of proteomic networks
    Kevin A Janes
    Biological Engineering Division and Cell Decision Processes Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Curr Opin Chem Biol 10:73-80. 2006
    ..No single model can achieve all these goals, however, which is why it is critical to prioritize biological questions before specifying a particular modeling approach...
  34. ncbi request reprint Applying computational modeling to drug discovery and development
    Neil Kumar
    Department of Chemical Engineering, Pfizer Research Technology Center, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Drug Discov Today 11:806-11. 2006
    ..Specific examples demonstrate how companies can employ these computational models to improve the efficiency of transforming targets into therapies...
  35. pmc Quantitative analysis of Akt phosphorylation and activity in response to EGF and insulin treatment
    Neil Kumar
    Department of Chemical Engineering, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Biochem Biophys Res Commun 354:14-20. 2007
    ..In sum, using a quantitative approach to study Akt activation identified ligand-dependent limits for the use of T308 or S473 as proxies for kinase activity and suggests the coregulation of Akt phosphorylation and dephosphorylation...
  36. ncbi request reprint Effects of Bcl-2 levels on Fas signaling-induced caspase-3 activation: molecular genetic tests of computational model predictions
    Fei Hua
    Center for Cancer Research and Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    J Immunol 175:985-95. 2005
    ..Finally, we demonstrate that the relative dominance of type I vs type II pathways can be switched by varying particular signaling component levels without changing network structure...
  37. pmc Computational model for cell migration in three-dimensional matrices
    Muhammad H Zaman
    Whitehead Institute for Biomedical Research, Biological Engineering Division, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, 02142, USA
    Biophys J 89:1389-97. 2005
    ..As one particular sample manifestation of these effects, the optimal levels of cell receptor expression and matrix ligand density yielding maximal migration are dependent on matrix mechanical compliance...
  38. ncbi request reprint Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow
    Carlos E Semino
    Center for Biomedical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, NE47 383, MIT, Cambridge, MA 02139, USA
    Exp Cell Res 312:289-98. 2006
    ....
  39. pmc Self-organization of polarized cell signaling via autocrine circuits: computational model analysis
    Ivan V Maly
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biophys J 86:10-22. 2004
    ..We additionally offer particular suggestions for critical nodes in the EGFR signaling circuits governing this self-organization capability...
  40. ncbi request reprint Bayesian analysis of signaling networks governing embryonic stem cell fate decisions
    Peter J Woolf
    Department of Chemical Engineering, University of Michigan, Room 3320, G G Brown Building, 2300 Hayward Street, Ann Arbor, MI 48109 2125, USA
    Bioinformatics 21:741-53. 2005
    ..Our experimental dataset includes measurements for 28 signaling protein phosphorylation states across 16 different factorial combinations of cytokine and matrix stimuli as reported previously...
  41. ncbi request reprint A model for mechanotransduction in cardiac muscle: effects of extracellular matrix deformation on autocrine signaling
    Ivan V Maly
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Ann Biomed Eng 32:1319-35. 2004
    ..These predictions point to the potential capabilities of the EGFR autocrine signaling circuit in mechanotransduction and suggest a new perspective on the cardiac hypertrophic response...
  42. pmc Integrated mechanistic and data-driven modelling for multivariate analysis of signalling pathways
    Fei Hua
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J R Soc Interface 3:515-26. 2006
    ..In conclusion, our framework provides a novel approach to understand the multivariate dependencies among molecules in complex networks, and can potentially be used to identify combinatorial targets for therapeutic interventions...
  43. ncbi request reprint Modeling of signal-response cascades using decision tree analysis
    Sampsa Hautaniemi
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Bioinformatics 21:2027-35. 2005
    ..we conclude that decision tree methodology may facilitate elucidation of signal-response cascade relationships and generate experimentally testable predictions, which can be used as directions for future experiments...
  44. doi request reprint A hybrid continuum-discrete modelling approach to predict and control angiogenesis: analysis of combinatorial growth factor and matrix effects on vessel-sprouting morphology
    Anusuya Das
    Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    Philos Trans A Math Phys Eng Sci 368:2937-60. 2010
    ..Thus, this model can be used to cluster sprout morphology as a function of various influencing factors...
  45. pmc Interstitial fluid flow intensity modulates endothelial sprouting in restricted Src-activated cell clusters during capillary morphogenesis
    Rodrigo Hernández Vera
    Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Tissue Eng Part A 15:175-85. 2009
    ..Src (pSrc)) at the monolayer, suggesting that the transduction pathway in charge of sensing the mechanical stimulus induced by flow is promoting predetermined mechanically sensitive areas (pSrc) to undergo capillary morphogenesis..
  46. pmc Impaired SHP2-mediated extracellular signal-regulated kinase activation contributes to gefitinib sensitivity of lung cancer cells with epidermal growth factor receptor-activating mutations
    Matthew J Lazzara
    Department of Biological Engineering and Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 70:3843-50. 2010
    ..This multivariate alteration of the network governing cellular response to gefitinib, which we term "oncogene imbalance," portends a potentially broader ability to treat gefitinib-resistant NSCLC...
  47. ncbi request reprint Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor necrosis-factor-induced apoptosis
    Kathryn Miller-Jensen
    Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Sci 119:3788-98. 2006
    ..The phenotypic and intracellular synergy between Adv and TNF may have implications for interpreting cellular responses in gene-therapy and laboratory applications...
  48. ncbi request reprint Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules
    Yi Zhang
    Biological Engineering Division, Massachusetts Institute of Technnology, Cambridge, Massachusetts 02139, USA
    Mol Cell Proteomics 4:1240-50. 2005
    ..Additional analysis and modeling of the data generated in this study are likely to yield more sophisticated models of receptor tyrosine kinase-initiated signal transduction, trafficking, and regulation...
  49. pmc Microarchitecture of three-dimensional scaffolds influences cell migration behavior via junction interactions
    Brendan A C Harley
    Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Biophys J 95:4013-24. 2008
    ..Strut junction interactions affect local directional persistence as well as cell speed at and away from the junctions, providing a new biophysical mechanism for the governance of cell motility by the extracellular microstructure...
  50. ncbi request reprint Cue-signal-response analysis of TNF-induced apoptosis by partial least squares regression of dynamic multivariate data
    Kevin A Janes
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Comput Biol 11:544-61. 2004
    ..Importantly, informative protein predictors of cell responses are always multivariate, demonstrating the multicomponent nature of the decision process...
  51. ncbi request reprint A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis
    Kevin A Janes
    Biological Engineering Division, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 310:1646-53. 2005
    ..Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set...
  52. pmc Directional persistence of EGF-induced cell migration is associated with stabilization of lamellipodial protrusions
    Brian D Harms
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biophys J 88:1479-88. 2005
    ....
  53. pmc Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks
    Alejandro Wolf-Yadlin
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:5860-5. 2007
    ..Using this approach, it should now be possible to routinely monitor the phosphorylation status of hundreds of nodes across multiple biological conditions...
  54. ncbi request reprint EGF-receptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation
    Elizabeth J Joslin
    Department of Biological Engineering, MIT, Cambridge, MA 02139, USA
    J Cell Sci 120:3688-99. 2007
    ..Thus, in our mammary epithelial cell system, migration and proliferation are differentially sensitive to the mode of EGF ligand presentation...
  55. pmc Global network analysis of phenotypic effects: protein networks and toxicity modulation in Saccharomyces cerevisiae
    Maya R Said
    Digital Signal Processing Group, Department of Electrical Engineering and Computer Science, and Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:18006-11. 2004
    ..These results have potential implications for understanding toxicity-modulating processes relevant to a number of human diseases, including cancer and aging...
  56. ncbi request reprint Coregulation of epidermal growth factor receptor/human epidermal growth factor receptor 2 (HER2) levels and locations: quantitative analysis of HER2 overexpression effects
    Bart S Hendriks
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 63:1130-7. 2003
    ..We anticipate that this model should ultimately be useful in parsing the relative contributions of direct effects of HER2 via signaling vis-a-vis indirect effects of HER2 via modification of EGFR signaling...
  57. pmc Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis
    Muhammad H Zaman
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 103:10889-94. 2006
    ..Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments...
  58. pmc An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells
    Brian A Joughin
    The David H Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA
    Mol Biosyst 5:59-67. 2009
    ..g. casein kinase II (CK2)) in cell proliferation downstream of EGFR signaling...
  59. ncbi request reprint Parsing the effects of binding, signaling, and trafficking on the mitogenic potencies of granulocyte colony-stimulating factor analogues
    Casim A Sarkar
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 4307, USA
    Biotechnol Prog 19:955-64. 2003
    ....
  60. pmc RAS mutations affect tumor necrosis factor-induced apoptosis in colon carcinoma cells via ERK-modulatory negative and positive feedback circuits along with non-ERK pathway effects
    Pamela K Kreeger
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts02139, USA
    Cancer Res 69:8191-9. 2009
    ....
  61. ncbi request reprint Integrating cell-level kinetic modeling into the design of engineered protein therapeutics
    Balaji M Rao
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Biotechnol 23:191-4. 2005
    ..Interpretation of these processes will require mathematical models that are refined in combination with relevant data derived from quantitative assays, to correctly set biophysical objectives for protein design...
  62. pmc Multipathway kinase signatures of multipotent stromal cells are predictive for osteogenic differentiation: tissue-specific stem cells
    Manu O Platt
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Stem Cells 27:2804-14. 2009
    ....
  63. ncbi request reprint Multiple signaling pathways mediate compaction of collagen matrices by EGF-stimulated fibroblasts
    Kirsty D Smith
    Biological Engineering Division, 56 341 MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Exp Cell Res 312:1970-82. 2006
    ..Our findings have thus identified key signals downstream of EGFR, which integrate in a complex manner to generate and transmit contractile forces to yield matrix deformation...
  64. pmc Cardiomyocyte hypertrophy and degradation of connexin43 through spatially restricted autocrine/paracrine heparin-binding EGF
    Jun Yoshioka
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02139, USA
    Proc Natl Acad Sci U S A 102:10622-7. 2005
    ..These findings demonstrate how cells can coordinate remodeling with their immediate neighboring cells with highly localized extracellular EGF signaling...
  65. ncbi request reprint Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus
    Lily Y Koo
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Sci 115:1423-33. 2002
    ..These results support previous studies showing that biophysical cues such as ligand spatial arrangement and extracellular matrix rigidity are central to the governance of cell responses to the external environment...
  66. ncbi request reprint Cell population dynamics model for deconvolution of murine embryonic stem cell self-renewal and differentiation responses to cytokines and extracellular matrix
    Wendy A Prudhomme
    Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames Street, 56 341, Cambridge, Massachusetts 02139, USA
    Biotechnol Bioeng 88:264-72. 2004
    ..Our approach facilitates interpretation of relationships underlying effects of external cues on cell responses in differentiating cultures via intracellular signals...
  67. pmc Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context
    Elizabeth J Joslin
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Biosyst 6:1293-306. 2010
    ..Our results suggest that the transactivation circuit acts as a context-dependent integrator and amplifier of multiple extracellular signals and that signal integration can effectively occur at multiple points in the EGFR pathway...
  68. ncbi request reprint Parsing ERK activation reveals quantitatively equivalent contributions from epidermal growth factor receptor and HER2 in human mammary epithelial cells
    Bart S Hendriks
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Biol Chem 280:6157-69. 2005
    ....
  69. ncbi request reprint Affinity regulates spatial range of EGF receptor autocrine ligand binding
    Ann DeWitt
    Department of Chemical Engineering, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Dev Biol 250:305-16. 2002
    ..Our experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling...
  70. ncbi request reprint The response of human epithelial cells to TNF involves an inducible autocrine cascade
    Kevin A Janes
    Center for Cell Decision Processes, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cell 124:1225-39. 2006
    ..quot; Time-dependent crosstalk of synergistic and antagonistic autocrine circuits may serve to link cellular responses to the local environment...
  71. ncbi request reprint Rational cytokine design for increased lifetime and enhanced potency using pH-activated "histidine switching"
    Casim A Sarkar
    Department of Chemical Engineering, Biotechnology Processing Center, Massachusetts Institute of Technology, Cambridge, MA 02139 4307, USA
    Nat Biotechnol 20:908-13. 2002
    ....
  72. ncbi request reprint Microfluidic shear devices for quantitative analysis of cell adhesion
    Hang Lu
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Anal Chem 76:5257-64. 2004
    ..In agreement with established literature, we show that fibroblasts cultured in the combined device reduced their adhesion strength to the substrate in response to epidermal growth factor stimulation...
  73. pmc A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis
    Ulrike Philippar
    Massachusetts Institute of Technology, Koch Institute, Cambridge, MA 02139, USA
    Dev Cell 15:813-28. 2008
    ..Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels...
  74. ncbi request reprint Causal protein-signaling networks derived from multiparameter single-cell data
    Karen Sachs
    Biological Engineering Division, Massachusetts Institute of Technology MIT, Cambridge, MA 02139, USA
    Science 308:523-9. 2005
    ..Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells...
  75. pmc Epidermal growth factor-induced enhancement of glioblastoma cell migration in 3D arises from an intrinsic increase in speed but an extrinsic matrix- and proteolysis-dependent increase in persistence
    Hyung Do Kim
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Biol Cell 19:4249-59. 2008
    ..Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance...
  76. ncbi request reprint A high-throughput quantitative multiplex kinase assay for monitoring information flow in signaling networks: application to sepsis-apoptosis
    Kevin A Janes
    Biological Engineering Division, Massachusetts Institute of Technology, 400 Main Street, Cambridge, MA 02139, USA
    Mol Cell Proteomics 2:463-73. 2003
    ..Thus, sampling parallel nodes in the intracellular signaling network identified part of the molecular mechanism underlying the efficacy of insulin in the treatment of human sepsis...
  77. doi request reprint An inducible autocrine cascade regulates rat hepatocyte proliferation and apoptosis responses to tumor necrosis factor-alpha
    Benjamin D Cosgrove
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Hepatology 48:276-88. 2008
    ..Exogenous TGF-alpha can either enhance or diminish apoptosis in adenoviral vector-treated and TNF-treated hepatocytes, in a biphasic relationship also mediated by autocrine IL-1alpha/beta feedback...
  78. ncbi request reprint High-affinity CD25-binding IL-2 mutants potently stimulate persistent T cell growth
    Balaji M Rao
    Department of Chemical Engineering, Massachusetts Institute of Technology, Building 66 552, 77 Massachusetts Avenue, Cambridge, Massachusetts 01239, USA
    Biochemistry 44:10696-701. 2005
    ....
  79. ncbi request reprint Collecting and organizing systematic sets of protein data
    John G Albeck
    Center for Cell Decision Processes, Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Rev Mol Cell Biol 7:803-12. 2006
    ..The key is to use several measurement technologies simultaneously and, recognizing each of their limits, to assemble a self-consistent compendium of systematic data...
  80. ncbi request reprint Multipathway model enables prediction of kinase inhibitor cross-talk effects on migration of Her2-overexpressing mammary epithelial cells
    Neil Kumar
    Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mol Pharmacol 73:1668-78. 2008
    ..We conclude that a quantitative, multipathway modeling approach can provide a significant advance toward comprehending kinase inhibitor efficacy in the face of off-target and pathway cross-talk effects...
  81. pmc Epi-allelic Erk1 and Erk2 knockdown series for quantitative analysis of T cell Erk regulation and IL-2 production
    Lucia Wille
    Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States
    Mol Immunol 44:3085-91. 2007
    ..The effect of the shRNA-mediated knockdowns in reducing IL-2 production was observed to be stronger than that arising from pharmacological MEK inhibition at comparable degrees of ERK1/2 phosphorylation levels...
  82. pmc Modeling HER2 effects on cell behavior from mass spectrometry phosphotyrosine data
    Neil Kumar
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS Comput Biol 3:e4. 2007
    ..Thus, a PLSR modeling approach reveals critical signaling processes regulating HER2-mediated cell behavior...
  83. pmc The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release
    Robin N Prince
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Cell Sci 123:2308-18. 2010
    ....
  84. pmc A high-throughput migration assay reveals HER2-mediated cell migration arising from increased directional persistence
    Neil Kumar
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Biophys J 91:L32-4. 2006
    ..Observed consistent increases in persistence associated with HER2 overexpression indicate a prospective mechanism for invasiveness previously documented in HER2-overexpressing human breast tumors...
  85. ncbi request reprint A multiplexed homogeneous fluorescence-based assay for protein kinase activity in cell lysates
    Melissa D Shults
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Methods 2:277-83. 2005
    ..This assay platform is immediately useful for studying protein kinase signaling in crude cellular extracts...
  86. ncbi request reprint Quantitative methods for developing Fc mutants with extended half-lives
    Daniel T Kamei
    Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Biotechnol Bioeng 92:748-60. 2005
    ..This Fc recycling parameter was found to be correlated with binding affinity, but captures the pH dependent nature of the interaction between Fc and FcRn and may serve as an additional screen following combinatorial experiments...
  87. pmc Multivariate proteomic analysis of murine embryonic stem cell self-renewal versus differentiation signaling
    Wendy Prudhomme
    Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:2900-5. 2004
    ..Our results demonstrate how a computational systems biology approach can elucidate key sets of intracellular signaling protein activities that combine to govern cell phenotypic responses to extracellular cues...
  88. pmc Kinetic model for lamellipodal actin-integrin 'clutch' dynamics
    Alice Macdonald
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell Adh Migr 2:95-105. 2008
    ..Overall, although this current model is quite simple it provides a useful foundation for more detailed models extending upon it...
  89. pmc Interleukin-7 receptor signaling network: an integrated systems perspective
    Megan J Palmer
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell Mol Immunol 5:79-89. 2008
    ..Analysis of IL-7 receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology...
  90. pmc Cytokine-associated drug toxicity in human hepatocytes is associated with signaling network dysregulation
    Benjamin D Cosgrove
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Mol Biosyst 6:1195-206. 2010
    ..Our findings highlight the critical role of kinase signaling in drug/cytokine hepatic cytotoxicity synergies and reveal that hepatic cytotoxicity responses are governed by multi-pathway signaling network balance...
  91. ncbi request reprint Mechanotransduction through growth-factor shedding into the extracellular space
    Daniel J Tschumperlin
    Physiology Program, Department of Environmental Health, Harvard School of Public Health, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 429:83-6. 2004
    ....
  92. ncbi request reprint Cutting to the chase: calpain proteases in cell motility
    Angela Glading
    Dept of Pathology, University of Pittsburgh VAMC, PA 15261, USA
    Trends Cell Biol 12:46-54. 2002
    ..Armed with this knowledge, the precise roles of calpains in inflammation, wound repair and tumor progression can be ascertained and offer novel therapeutic targets...
  93. ncbi request reprint Epidermal growth factor induces fibroblast contractility and motility via a protein kinase C delta-dependent pathway
    Akihiro Iwabu
    Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 279:14551-60. 2004
    ..Hence, we identify here a new pathway helping to govern cell motility, with PLC signaling playing a role in activation of PKCdelta to promote the acute phase of EGF-induced MLC activation...
  94. ncbi request reprint Understanding effects of matrix protease and matrix organization on directional persistence and translational speed in three-dimensional cell migration
    Muhammad H Zaman
    Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
    Ann Biomed Eng 35:91-100. 2007
    ..Our results show a bimodal dependence of speed and persistence on matrix pore size and suggest high sensitivity on MMP activity, which is in very good agreement with experimental studies carried out in 3D matrices...
  95. ncbi request reprint Motility signaled from the EGF receptor and related systems
    Alan Wells
    Department of Pathology, University of Pittsburgh, PA, USA
    Methods Mol Biol 327:159-77. 2006
    ..Herein we describe methods that measure the overall motility and its parameters as well as the biophysical processes extension, de-adhesion/retraction, and contraction...
  96. ncbi request reprint Calpain proteases in cell adhesion and motility
    Alan Wells
    Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Int Rev Cytol 245:1-16. 2005
    ....
  97. pmc Quantitative analysis of pathways controlling extrinsic apoptosis in single cells
    John G Albeck
    Department of Systems Biology, Harvard Medical School, WAB Room 438, 200 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 30:11-25. 2008
    ..Together, these findings provide a quantitative picture of caspase regulatory networks and their failure modes...
  98. ncbi request reprint Clonal evolution of stem and differentiated cells can be predicted by integrating cell-intrinsic and -extrinsic parameters
    Sowmya Viswanathan
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9
    Biotechnol Appl Biochem 42:119-31. 2005
    ..On the basis of all these results, we believe that our iterative experimental and computational approach has been found to be useful for the study of various stem-cell systems...
  99. pmc Flexible informatics for linking experimental data to mathematical models via DataRail
    Julio Saez-Rodriguez
    Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Bioinformatics 24:840-7. 2008
    ....
  100. pmc The membrane-anchoring domain of epidermal growth factor receptor ligands dictates their ability to operate in juxtacrine mode
    Jianying Dong
    Department of Pathology, Division of Cell Biology and Immunology, University of Utah, Salt Lake City, UT 84133, USA
    Mol Biol Cell 16:2984-98. 2005
    ..Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode...
  101. pmc The Na+/H+ exchanger regulatory factor stabilizes epidermal growth factor receptors at the cell surface
    Cheri S Lazar
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0650, USA
    Mol Biol Cell 15:5470-80. 2004
    ..Although the mechanisms differ, for both RTKs and G protein-coupled receptors, the overall effect of NHERF is to enhance the fraction of receptors present at the cell surface...

Research Grants17

  1. Computational Modeling of Cell Migration in 3D Matrices
    Douglas Lauffenburger; Fiscal Year: 2009
    ....
  2. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2004
    ..These findings may increase our opportunities to limit tumor spread by targeting novel intracellular enzymes. ..
  3. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2003
    ..These findings may increase our opportunities to limit tumor spread by targeting novel intracellular enzymes. ..
  4. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2002
    ..Lastly, this system will then be exploited as a vehicle for therapeutic interventions, one that accounts for the agent's effect on both the tumor and host tissue. ..
  5. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2002
    ..These findings may increase our opportunities to limit tumor spread by targeting novel intracellular enzymes. ..
  6. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2002
    ..The knowledge gained from these studies may help to control the cell migration in tissue engineering applications. ..
  7. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2001
    ..The knowledge gained from these studies may help to control the cell migration in tissue engineering applications. ..
  8. Cell Motility in Prostate Tumor Invasion
    Douglas Lauffenburger; Fiscal Year: 2001
    ..These findings may increase our opportunities to limit tumor spread by targeting novel intracellular enzymes. ..
  9. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 2000
    ..The knowledge gained from these studies may help to control the cell migration in tissue engineering applications. ..
  10. ENGINEERING INTEGRIN--MEDIATED CELL MIGRATION
    Douglas Lauffenburger; Fiscal Year: 1999
    ..The knowledge gained from these studies may help to control the cell migration in tissue engineering applications. ..
  11. Computational Modeling of Cell Migration in 3D Matrices
    Douglas A Lauffenburger; Fiscal Year: 2010
    ....