Browsing by Author "Sorger, Peter"

Now showing items 1-20 of 33

    • Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state 

      Fallahi‐Sichani, Mohammad; Becker, Verena; Izar, Benjamin; Baker, Gregory J; Lin, Jia‐Ren; Boswell, Sarah A; Shah, Parin; Rotem, Asaf; Garraway, Levi A; Sorger, Peter K (John Wiley and Sons Inc., 2017)
      Abstract Treatment of BRAF‐mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use ...

    • Analysis of growth factor signaling in genetically diverse breast cancer lines 

      Niepel, Mario; Hafner, Marc; Pace, Emily A; Chung, Mirra; Chai, Diana H; Zhou, Lili; Muhlich, Jeremy L; Schoeberl, Birgit; Sorger, Peter K (BioMed Central, 2014)
      Background: Soluble growth factors present in the microenvironment play a major role in tumor development, invasion, metastasis, and responsiveness to targeted therapies. While the biochemistry of growth factor-dependent ...

    • Biophysical Prediction of Protein-Peptide Interactions and Signaling Networks Using Machine Learning 

      Cunningham, Joseph; Koytiger, Grigoriy; Sorger, Peter; AlQuraishi, Mohammed (Springer Science and Business Media LLC, 2020-01-06)
      In mammalian cells, much of signal transduction is mediated by weak protein-protein interactions between globular peptide-binding domains (PBDs) and unstructured peptidic motifs in partner proteins. The number and diversity ...

    • Changing Mad2 Levels Affects Chromosome Segregation and Spindle Assembly Checkpoint Control in Female Mouse Meiosis I 

      Niault, Théodora; Hached, Khaled; Sotillo, Rocío; Sorger, Peter Karl; Maro, Bernard; Benezra, Robert; Wassmann, Katja (Public Library of Science, 2007)
      The spindle assembly checkpoint (SAC) ensures correct separation of sister chromatids in somatic cells and provokes a cell cycle arrest in metaphase if one chromatid is not correctly attached to the bipolar spindle. Prolonged ...

    • Creating and Analyzing Pathway and Protein Interaction Compendia for Modelling Signal Transduction Networks 

      Kirouac, Daniel C; Saez-Rodriguez, Julio; Swantek, Jennifer; Burke, John M; Lauffenburger, Douglas A; Sorger, Peter Karl (BioMed Central, 2012)
      Background: Understanding the information-processing capabilities of signal transduction networks, how those networks are disrupted in disease, and rationally designing therapies to manipulate diseased states require ...

    • Crystal Structure of the Yeast Inner Kinetochore Subunit cep3p 

      Bellizzi, John J. III; Sorger, Peter; Harrison, Stephen (Elsevier, 2007)
      In budding yeast, the four-protein CBF3 complex (Skp1p-Ctf13p-Cep3p-Ndc10p) initiates kinetochore assembly by binding to the CDEIII locus of centromeric DNA. A Cep3p dimer recruits a Ctf13p-Skp1p heterodimer and contacts ...

    • Decision-Tree Based Model Analysis for Efficient Identification of Parameter Relations Leading to Different Signaling States 

      Koch, Yvonne; Wolf, Thomas; Sorger, Peter K.; Eils, Roland; Brors, Benedikt (Public Library of Science, 2013)
      In systems biology, a mathematical description of signal transduction processes is used to gain a more detailed mechanistic understanding of cellular signaling networks. Such models typically depend on a number of parameters ...

    • Discrete Logic Modelling as a Means to Link Protein Signalling Networks with Functional Analysis of Mammalian Signal Transduction 

      Saez-Rodriguez, Julio; Alexopoulos, Leonidas G; Epperlein, Jonathan; Samaga, Regina; Lauffenburger, Douglas A; Klamt, Steffen; Sorger, Peter Karl (Nature Publishing Group, 2009)
      Large-scale protein signalling networks are useful for exploring complex biochemical pathways but do not reveal how pathways respond to specific stimuli. Such specificity is critical for understanding disease and designing ...

    • Evolution of Delayed Resistance to Immunotherapy in a Melanoma Responder 

      Liu, David; Lin, Jia-Ren; Robitschek, Emily; Kasumova, Gyulnara; Heyde, Alexander; Shi, Alvin; Kraya, Adam; Zhang, Gao; Moll, Tabea; Frederick, Dennie; Chen, Yu-An; Schapiro, Denis; Ho, Li-Lun; Bi, Kevin; Sahu, Avinash; Mei, Shaolin; Miao, Benchun; Sharova, Tatyana; Alvarez-Breckenridge, Christopher; Stocking, Jackson; Kim, Tommy; Fadden, Riley; Lawrence, Donald; Hoang, Mai; Cahill, Daniel; Maleh Mir, Mohsen; Nowak, Martin; Brastianos, Priscilla; Lian, Christine; Ruppin, Eytan; Izar, Benjamin; Herlyn, Meenhard; Van Allen, Eliezer; Nathanson, Katherine; Flaherty, Keith; Sullivan, Ryan; Kellis, Manolis; Sorger, Peter; Boland, Genevieve (Springer Nature, 2021-05-03)
      Despite initial responses, most melanoma patients develop resistance to immune checkpoint blockade (ICB). To understand the evolution of resistance, we studied 37 tumor samples over 9 years from a metastatic melanoma patient ...

    • Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis 

      Gaudet, Suzanne; Spencer, Sabrina L.; Chen, William Wei-Lun; Sorger, Peter Karl (Public Library of Science, 2012)
      Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand) variability ...

    • Fractional killing arises from cell-to-cell variability in overcoming a caspase activity threshold 

      Roux, Jérémie; Hafner, Marc; Bandara, Samuel; Sims, Joshua J; Hudson, Hannah; Chai, Diana; Sorger, Peter K (BlackWell Publishing Ltd, 2015)
      When cells are exposed to death ligands such as TRAIL, a fraction undergoes apoptosis and a fraction survives; if surviving cells are re-exposed to TRAIL, fractional killing is once again observed. Therapeutic antibodies ...

    • Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling 

      Aldridge, Bree Beardsley; Saez-Rodriguez, Julio; Muhlich, Jeremy; Sorger, Peter Karl; Lauffenburger, Douglas A. (Public Library of Science, 2009)
      When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a fuzzy logic framework to the analysis of a large, systematic dataset describing ...

    • Genome-Encoded Cytoplasmic Double-Stranded RNAs, Found in C9ORF72 ALS-FTD Brain, Propagate Neuronal Loss 

      Rodriguez, Steve; Sahin, Asli; Schrank, Benjamin R.; Al Lawati, Hawra; Costantino, Isabel; Benz, Eric; Fard, Darian; Albers, Alefiya; Cao, Luxiang; Gomez, Alexis; Evans, Kyle; Ratti, Elena; Cudkowicz, Merit; Frosch, Matthew; Talkowski, Michael; Sorger, Peter; Hyman, Bradley; Albers, Mark (Science Press / AAAS, 2021-07-07)
      Triggers of innate immune signaling in the CNS of amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD) patients remain elusive. We report the presence of cytoplasmic double-stranded RNA (cdsRNA), an ...

    • Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs 

      Hafner, Marc; Niepel, Mario; Chung, Mirra; Sorger, Peter K. (2016)
      Drug sensitivity and resistance are conventionally quantified by IC50 or Emax values, but these metrics are highly sensitive to the number of divisions taking place over the course of a response assay. The dependency of ...

    • Highly multiplexed imaging of single cells using a high-throughput cyclic immunofluorescence method 

      Lin, Jia-Ren; Fallahi-Sichani, Mohammad; Sorger, Peter K. (Nature Pub. Group, 2015)
      Single-cell analysis reveals aspects of cellular physiology not evident from population-based studies, particularly in the case of highly multiplexed methods such as mass cytometry (CyTOF) able to correlate the levels of ...

    • Input–Output Behavior of ErbB Signaling Pathways as Revealed by a Mass Action Model Trained against Dynamic Data 

      Chen, William Wei-Lun; Schoeberl, Birgit; Jasper, Paul J; Niepel, Mario; Nielsen, Ulrik B; Lauffenburger, Douglas A; Sorger, Peter Karl (Nature Publishing Group, 2009)
      The ErbB signaling pathways, which regulate diverse physiological responses such as cell survival, proliferation and motility, have been subjected to extensive molecular analysis. Nonetheless, it remains poorly understood ...

    • LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures 

      Duan, Qiaonan; Flynn, Corey; Niepel, Mario; Hafner, Marc; Muhlich, Jeremy L.; Fernandez, Nicolas F.; Rouillard, Andrew D.; Tan, Christopher M.; Chen, Edward Y.; Golub, Todd R.; Sorger, Peter K.; Subramanian, Aravind; Ma'ayan, Avi (Oxford University Press, 2014)
      For the Library of Integrated Network-based Cellular Signatures (LINCS) project many gene expression signatures using the L1000 technology have been produced. The L1000 technology is a cost-effective method to profile gene ...

    • The Logic of EGFR/ErbB Signaling: Theoretical Properties and Analysis of High-Throughput Data 

      Samaga, Regina; Saez-Rodriguez, Julio; Alexopoulos, Leonidas G.; Sorger, Peter Karl; Klamt, Steffen (Public Library of Science, 2009)
      The epidermal growth factor receptor (EGFR) signaling pathway is probably the best-studied receptor system in mammalian cells, and it also has become a popular example for employing mathematical modeling to cellular signaling ...

    • Logic-Based Models for the Analysis of Cell Signaling Networks 

      Morris, Melody K.; Saez-Rodriguez, Julio; Sorger, Peter Karl; Lauffenburger, Douglas A. (American Chemical Society, 2010)
      Computational models are increasingly used to analyze the operation of complex biochemical networks, including those involved in cell signaling networks. Here we review recent advances in applying logic-based modeling to ...

    • Lyapunov Exponents and Phase Diagrams Reveal Multi-Factorial Control over TRAIL-Induced Apoptosis 

      Aldridge, Bree Beardsley; Gaudet, Suzanne; Lauffenburger, Douglas A.; Sorger, Peter Karl (Nature Publishing Group, 2011)
      Receptor-mediated apoptosis proceeds via two pathways: one requiring only a cascade of initiator and effector caspases (type I behavior) and the second requiring an initiator–effector caspase cascade and mitochondrial outer ...