Profiling Drugs for Rheumatoid Arthritis that Inhibit Synovial Fibroblast Activation

Jones DS, Jenney AP, Swantek JL, Burke JM, Lauffenburger DA, Sorger PK. Profiling Drugs for Rheumatoid Arthritis that Inhibit Synovial Fibroblast Activation. Nature Chemical Biology. Epub 2016/10/31. doi: 10.1038/nchembio.2211 Abstract

Activation of synovial fibroblasts (SFs) contributes to rheumatoid arthritis (RA) by damaging synovial membranes and generating inflammatory cytokines that recruit immune cells to the joint. […]

Conservation of Protein Abundance Patterns Reveals the Regulatory Architecture of the EGFR-MAPK Pathway

Shi T, Niepel M, McDermott JE, Gao Y, Nicora CD, Chrisler WB, Markillie LM, Petyuk VA, Smith RD, Rodland KD, Sorger PK, Qian WJ, Wiley HS. Conservation of Protein Abundance Patterns Reveals the Regulatory Architecture of the EGFR-MAPK Pathway. Sci Signal. 2016;9(436):rs6. Epub 2016/07/14. doi: 10.1126/scisignal.aaf0891. PMID: 27405981; PMCID: PMC5036860. Abstract

Various genetic mutations associated […]

Growth Rate Inhibition Metrics Correct for Confounders in Measuring Sensitivity to Cancer Drugs

Hafner M, Niepel M, Chung M, Sorger PK. Growth Rate Inhibition Metrics Correct for Confounders in Measuring Sensitivity to Cancer Drugs. Nat Methods. 2016;13(6):521-7. Epub 2016/05/03. doi: 10.1038/nmeth.3853. PMID: 27135972; PMCID: PMC4887336. Abstract

Drug sensitivity and resistance are conventionally quantified by IC50 or Emax values, but these metrics are highly sensitive to the number of […]

Reproducibility Will Only Come with Data Liberation

AlQuraishi M, Sorger PK. Reproducibility Will Only Come with Data Liberation. Science translational medicine. 2016;8(339):339ed7. Epub 2016/05/20. doi: 10.1126/scitranslmed.aaf0968. PMID: 27194726.

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Dissecting the Multicellular Ecosystem of Metastatic Melanoma by Single-cell RNA-seq

Tirosh I, Izar B, Prakadan SM, Wadsworth MH, 2nd, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G, Fallahi-Sichani M, Dutton-Regester K, Lin JR, Cohen O, Shah P, Lu D, Genshaft AS, Hughes TK, Ziegler CG, Kazer SW, Gaillard A, Kolb KE, Villani AC, Johannessen CM, Andreev AY, Van Allen EM, Bertagnolli […]

Highly Multiplexed Imaging of Single Cells Using a High-throughput Cyclic Immunofluorescence Method

Lin JR, Fallahi-Sichani M, Sorger PK. Highly Multiplexed Imaging of Single Cells Using a High-throughput Cyclic Immunofluorescence Method. Nat Commun. 2015;6:8390. Epub 2015/09/25. doi: 10.1038/ncomms9390. PMID: 26399630; PMCID: PMC4587398. Abstract

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) […]

Fractional Killing Arises from Cell-to-cell Variability in Overcoming a Caspase Activity Threshold

Roux J, Hafner M, Bandara S, Sims JJ, Hudson H, Chai D, Sorger PK. Fractional Killing Arises from Cell-to-cell Variability in Overcoming a Caspase Activity Threshold. Mol Syst Biol. 2015;11(5):803. Epub 2015/05/09. doi: 10.15252/msb.20145584. PMID: 25953765; PMCID: PMC4461398. Abstract

When cells are exposed to death ligands such as TRAIL, a fraction undergoes apoptosis and a […]

Surviving Apoptosis: Life-death Signaling in Single Cells

Flusberg DA, Sorger PK. Surviving Apoptosis: Life-death Signaling in Single Cells. Trends in cell biology. 2015. Epub 2015/04/30. doi: 10.1016/j.tcb.2015.03.003. PMID: 25920803; PMCID: PMC4570028. Abstract

Tissue development and homeostasis are regulated by opposing pro-survival and pro-death signals. An interesting feature of the Tumor Necrosis Factor (TNF) family of ligands is that they simultaneously activate opposing […]

Systematic Analysis of BRAFV600E Melanomas Reveals a Role for JNK/c-Jun Pathway in Adaptive Resistance to Drug-induced Apoptosis

Fallahi-Sichani M, Moerke NJ, Niepel M, Zhang T, Gray NS, Sorger PK. Systematic Analysis of BRAFV600E Melanomas Reveals a Role for JNK/c-Jun Pathway in Adaptive Resistance to Drug-induced Apoptosis. Mol Syst Biol. 2015;11(3):797. Epub 2015/03/31. doi: 10.15252/msb.20145877. PMID: 25814555; PMCID: PMC4380931. Abstract

Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary […]

A Multiscale Statistical Mechanical Framework Integrates Biophysical and Genomic Data to Assemble Cancer Networks

AlQuraishi M, Koytiger G, Jenney A, MacBeath G, and Sorger PK (2014). A Multiscale Statistical Mechanical Framework Integrates Biophysical and Genomic Data to Assemble Cancer Networks. Nature genetics 46(12), 1363-1371. PMCID: 4244270 PMID: 25362484. Abstract

Functional interpretation of genomic variation is critical to understanding human disease, but it remains difficult to predict the effects of […]