Publications « Sorger Lab

Classic and Contemporary Approaches to Modeling Biochemical Reactions

Chen, W.W., Niepel, M., and Sorger, P.K. (2010). Classic and Contemporary Approaches to Modeling Biochemical Reactions. Genes Dev 24, 1861-1875. PMC2932968. Abstract

Recent interest in modeling biochemical networks raises questions about the relationship between often complex mathematical models and familiar arithmetic concepts from classical enzymology, and also about connections between modeling and experimental data. This […]

Dissecting Variability in Responses to Cancer Chemotherapy Through Systems Pharmacology

Yang, R., Niepel, M., Mitchison, T.K., and Sorger, P.K. (2010). Dissecting Variability in Responses to Cancer Chemotherapy through Systems Pharmacology. Clin Pharmacol Ther 88, 34-38. PMC2941986. Abstract

Variability in patient responses to even the most potent and targeted therapeutics is now the primary challenge facing drug discovery and patient care, particularly in oncology and immune […]

Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes

Alexopoulos, L.G., Saez-Rodriguez, J., Cosgrove, B.D., Lauffenburger, D.A., and Sorger, P.K. (2010). Networks Inferred from Biochemical Data Reveal Profound Differences in Toll-Like Receptor and Inflammatory Signaling between Normal and Transformed Hepatocytes. Mol Cell Proteomics 9, 1849-1865. PMC2938121. Abstract

Systematic study of cell signaling networks increasingly involves high throughput proteomics, transcriptional profiling, and automated literature mining […]

Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges

Prill RJ, Marbach D, Saez-Rodriguez J, Sorger PK, Alexopoulos LG, Xue X, Clarke ND, Altan-Bonnet G, Stolovitzky G. (2010) PLoS ONE 5(2): e9202. PMC2826397 Background

Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets. The onslaught of data is accelerating as molecular profiling technology evolves. […]

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

Saez-Rodriguez J, Alexopoulos LG, Epperlein J, Samaga R, Lauffenburger DA, Klamt S, Sorger PK. (2009) Mol Syst Biol 5: 331.

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 drugs. Here we describe a […]

Roles for the Conserved spc105p/kre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint

Pagliuca C, Draviam VM, Marco E, Sorger PK, De Wulf P. (2009) PLoS ONE 4(10): e7640. PMC2764089

Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain approximately 70 subunits that assemble on centromeric DNA in a hierarchical […]

Non-Genetic Cell-to-Cell Variability and the Consequences for Pharmacology

Niepel M, Spencer SL, Sorger PK. (2009) Curr Opin Chem Biol 13(5-6): 556-61.

Recent advances in single-cell assays have focused attention on the fact that even members of a genetically identical group of cells or organisms in identical environments can exhibit variability in drug sensitivity, cellular response, and phenotype. Underlying much of this variability is […]

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

Samaga R, Saez-Rodriguez J, Alexopoulos LG, Sorger PK, Klamt S. (2009) PLoS Comput Biol 5(8): e1000438.

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 networks. Dynamic models have the highest explanatory […]

Synergistic Drug-Cytokine Induction of Hepatocellular Death as an in vitro Approach for the Study of Inflammation-Associated Idiosyncratic Drug Hepatotoxicity

Cosgrove BD, King BM, Hasan MA, Alexopoulos LG, Farazi PA, Hendriks BS, Griffith LG, Sorger PK, Tidor B, Xu JJ, Lauffenburger DA. (2009) Toxicol Appl Pharmacol 237(3): 317-30.

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration […]

Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis

Spencer SL, Gaudet S, Albeck JG, Burke JM, Sorger PK. (2009) Nature 459(7245): 428-32.

In microorganisms, noise in gene expression gives rise to cell-to-cell variability in protein concentrations. In mammalian cells, protein levels also vary and individual cells differ widely in their responsiveness to uniform physiological stimuli. In the case of apoptosis mediated by TRAIL […]

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