Common and Cell-type Specific Responses to Anti-cancer Drugs Revealed by High Throughput Transcript Profiling

Niepel M, Hafner M, Duan Q, Wang Z, Paull EO, Chung M, Lu X, Stuart JM, Golub TR, Subramanian A, Ma’ayan A, Sorger PK. Common and cell-type specific responses to anti-cancer drugs revealed by high throughput transcript profiling. Nat Commun. 2017 Oct 30;8(1):1186. PMCID: PMC5662764 Abstract

More effective use of targeted anti-cancer drugs depends on […]

GRcalculator: An Online Tool for Calculating and Mining Dose-response Data

Clark NA, Hafner M, Kouril M, Williams EH, Muhlich JL, Pilarczyk M, Niepel M, Sorger PK, Medvedovic M. GRcalculator: an online tool for calculating and mining dose-response data. BMC Cancer. 2017 Oct 24;17(1):698. PMCID: PMC5655815 Abstract

BACKGROUND: Quantifying the response of cell lines to drugs or other perturbagens is the cornerstone of pre-clinical drug development […]

Multiplexed Exchange-PAINT Imaging Reveals Ligand-dependent EGFR and Met Interactions in the Plasma Membrane

Werbin JL, Avendaño MS, Becker V, Jungmann R, Yin P, Danuser G, Sorger PK. Multiplexed Exchange-PAINT imaging reveals ligand-dependent EGFR and Met interactions in the plasma membrane. Sci Rep. 2017 Sep 22;7(1):12150. PMCID: PMC5610318 Abstract

Signal transduction by receptor tyrosine kinases (RTKs) involves complex ligand- and time-dependent changes in conformation and modification state. High resolution […]

Designing Drug-Response Experiments and Quantifying their Results

Hafner M, Niepel M, Subramanian K, Sorger PK. Designing Drug-Response Experiments and Quantifying their Results. Curr Protoc Chem Biol. 2017 Jun 19;9(2):96–116. PMID: 28628201 Abstract

We developed a Python package to help in performing drug-response experiments at medium and high throughput and evaluating sensitivity metrics from the resulting data. In this article, we describe the […]

Measuring Cancer Drug Sensitivity and Resistance in Cultured Cells

Niepel M, Hafner M, Chung M, Sorger PK. Measuring Cancer Drug Sensitivity and Resistance in Cultured Cells. Curr Protoc Chem Biol. 2017 Jun 19;9(2):55–74. PMID: 28628199 Abstract

Measuring the potencies of small-molecule drugs in cell lines is a critical aspect of preclinical pharmacology. Such experiments are also prototypical of high-throughput experiments in multi-well plates. The […]

Alternative Drug Sensitivity Metrics Improve Preclinical Cancer Pharmacogenomics

Hafner M, Niepel M, Sorger PK. Alternative drug sensitivity metrics improve preclinical cancer pharmacogenomics. Nature biotechnology. 2017 Jun 7;35(6):500–502. PMID: 28591115

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Fundamental Trade-offs Between Information Flow in Single Cells and Cellular Populations

Suderman R, Bachman JA, Smith A, Sorger PK, Deeds EJ. Fundamental trade-offs between information flow in single cells and cellular populations. Proceedings of the National Academy of Sciences of the United States of America. 2017 May 30;114(22):5755–5760. PMID: 28500273; PMCID: 5465904 Abstract

Signal transduction networks allow eukaryotic cells to make decisions based on information about […]

Deletion of the MAD2L1 Spindle Assembly Checkpoint Gene is Tolerated in Mouse Models of Acute T-cell Lymphoma and Hepatocellular Carcinoma

Foijer F, Albacker LA, Bakker B, Spierings DC, Yue Y, Xie SZ, Davis SH, Lutum-Jehle A, Takemoto D, Hare B, Furey B, Bronson RT, Lansdorp PM, Bradley A, Sorger PK. Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. eLife [Internet]. 2017 Mar 20;6. […]

Structure-guided Development of Covalent TAK1 Inhibitors

Tan L, Gurbani D, Weisberg EL, Hunter JC, Li L, Jones DS, Ficarro SB, Mowafy S, Tam CP, Rao S, Du G, Griffin JD, Sorger PK, Marto JA, Westover KD, Gray NS. Structure-guided development of covalent TAK1 inhibitors. Bioorganic & medicinal chemistry. 2017 Feb 1;25(3):838–846. PMID: 28011204; PMCID: 5484537 Abstract

TAK1 (transforming growth factor-beta-activated kinase […]

Adaptive Resistance of Melanoma Cells to RAF Inhibition via Reversible Induction of a Slowly Dividing de-differentiated State

Fallahi-Sichani M, Becker V, Izar B, Baker GJ, Lin JR, Boswell SA, Shah P, Rotem A, Garraway LA, Sorger PK. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state. Molecular systems biology. 2017 Jan 9;13(1):905. PMID: 28069687; PMCID: 5248573 Abstract

Treatment of BRAF-mutant melanomas with MAP kinase […]