研究领域
Single-cell imaging of kinase networks regulating cell proliferation and metabolism
Research in my lab is focused on understanding the mechanisms of information flow in signal transduction networks controlling cell growth, survival, and metabolism. While traditional studies of signaling have focused on the identity of the proteins involved in such cascades and the nature of the interactions between them, we are studying how the activation dynamics of these pathways encode specific information for the cell. Our goal is to address the question of how specificity is achieved when the same small group of pathways (including ERK, Akt, Hippo, and mTOR) controls a diverse set of cellular behaviors (proliferation, growth, migration, apoptosis, autophagy, and differentiation). To decipher this signaling “code”, we combine computational models with live cell data from genetically encoded fluorescent biosensors for phosphorylation or transcription events. By tracking signaling events in many individual cells and associating them with corresponding cellular phenotypes and the activation of specific genes, we aim to identify temporal signaling programs that drive cell behaviors. This knowledge can then be used to improve the results of therapeutic interventions in cancer and other diseases, by predicting the cellular responses to signaling inhibitors.
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Sparta B, Pargett M, Minguet M, Distor K, Bell G, Albeck JG. (2015) Receptor-Level Mechanisms Are Required for EGF-Stimulated ERK Activity Pulses. Journal of Biological Chemistry pii: jbc.M115.662247
Selimkhanov J, Taylor B, Yao J, Pilko A, Albeck J, Hoffmann A, Tsimring L, Wollman R. (2014) Systems biology. Accurate information transmission through dynamic biochemical signaling networks. Science 346(6215):1370-3.
Shestov AA, Liu X, Ser Z, Cluntun AA, Hung YP, Huang L, Kim D, Le A, Yellen G, Albeck JG, Locasale JW. (2014) Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step. eLife doi: 10.7554/eLife.03342.
Albeck JG, Mills GB, Brugge JS. (2013) Frequency-modulated pulses of ERK activity transmit quantitative proliferation signals. Molecular Cell 49:1-13.
Worster DT, Schmelzle T, Solimini NL, Lightcap ES, Millard B, Mills GB, Brugge JS, Albeck JG. (2012) Akt and ERK Control the Proliferative Response of Mammary Epithelial Cells to the Growth Factors IGF-1 and EGF Through the Cell Cycle Inhibitor p57Kip2. Science Signaling 5(214):ra19.
Hung YP, Albeck JG, Tantama M, Yellen G. (2011) Imaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor. Cell Metabolism 14(4):545-54.
Albeck JG, Brugge JS. (2011) Uncovering a tumor suppressor for triple-negative breast cancers. Cell 144(5):638-40.
Spencer SL*, Gaudet S*, Albeck JG, Burke JM, Sorger PK. (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 459(7245):428-32.
Albeck JG*, Burke JM*, Spencer SL, Lauffenburger DA, Sorger PK. (2008) Modeling a snap-action, variable-delay switch controlling extrinsic cell death. PLoS Biology 6(12):2831-52.
Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK. (2008) Quantitative analysis of pathways controlling extrinsic apoptosis in single cells. Molecular Cell 30(1):11-25.
Albeck JG, MacBeath G, White FM, Sorger PK, Lauffenburger DA, Gaudet S. (2006) Collecting and organizing systematic sets of protein data. Nature Reviews Molecular Cell Biology 7(11):803-12.