

Suzanne GaudetBiosketch:Research Scientist, CDP Center, Sorger lab, MIT, 2003-present Primary CollaboratorsBirgit Schoeberl, Merrimack Pharmaceutical Research FocusIn the human body, cells are constantly being challenged by multiple extracellular stimuli. While a lot is known about the signals and behaviors induced by each type of stimulus, it is still unclear how the responses to multiple stimuli are integrated and affect cell behavior. At the CDP Center, I am using biochemical and cell biological tools to measure quantitatively various signals in human cells treated with conflicting prodeath (TNF) and prosurvival (EGF and insulin) cytokines. Heterogeneous data from four scientists have now been merged into a self-consistent compendium, characterizing the responses of these cells to TNF, EGF and insulin over time, and following perturbations with specific inhibitors. This compendium is being mined computationally to gain insights as to how cell process conflicting signals to execute a cell death/survival decision. In parallel, I have been working with Birgit Schoeberl (now at Merrimack Pharmaceutical) to develop a mechanistic, ODE-based model of TNF-induced signaling. We have used quantitative data on signals triggered by TNF treatment to determine an optimal parameter set for the cell lines we are studying. We are now at the exciting stage of experimentally testing hypotheses that were derived from this model. CDP PublicationsJanes, K.A., Gaudet S., Albeck J.G., Nielsen U.B., Lauffenburger D.A., and Sorger P.K., “Autocrine crosstalk in the response of human cells to apoptotic and mitogenic stimuli” Cell, 124 : 1225-1239. Janes K.A., Albeck J.G., Gaudet S., Sorger P.K., Lauffenburger D.A., et Yaffe M.B., “A Systems Model of Signaling Identifies a Molecular Basis Set that Predicts Cytokine-Induced Apoptosis” Science, 310 : 1646-1653. Gaudet S., Janes K.A., Albeck J.G., Pace E.A., Lauffenburger D.A., and Sorger P.K., (2005) “A compendium of signals and responses triggered by prodeath and prosurvival cytokines”, Mol. Cell. Proteomics, 4:1569-1590. El-Ali J., Gaudet S., Gunther A., Sorger P.K, and Jensen K.F. (2005) “Rapid cell stimulus and lysis in a microfluidic device with segmented gas-liquid flow”, Anal. Chem., 11:3629-36. Janes K.A., Kelly J.R., Gaudet S., Albeck J.G., Sorger P.K., and Lauffenburger D.A., (2004) “Cue-signal-response analysis of the TNF-induced apoptosis by partial least squares regression of dynamic multivariate data’, J. Comput. Biol., 11: 544-61. Lu. H., Gaudet S., Schmidt M.A., and Jensen K.F. (2004) “A Microfluidic Device for Subcellular Organelle Sorting”, Anal. Chem. 76: 5705-12. Fritz J., Cooper E.B., Gaudet S., Sorger P.K., and Manalis S.R. (2002) “Electronic detection of DNA by its intrinsic molecular charge”, PNAS 99: 14142-6. |
||