BBS Faculty Member - Suzanne Gaudet

Suzanne Gaudet

Department of Cancer Biology, DFCI
Department of Genetics, HMS

Dana Farber Cancer Institute
Smith Building, Room 836B
450 Brookline Ave.
Boston, MA 02215
Tel: 617-632-4269
Fax: 617-632-5739
Email: suzanne_gaudet@hms.harvard.edu
Lab Members: 2 postdoctoral fellows, 2 graduate students, 1 research technician
Visit my lab page here.



In the human body, the behavior of cells is choreographed by their response to hundreds of proteins or small molecule ligands. Ligands regulate growth, proliferation, migration, differentiation and even cell death. We want to understand how ligands exert their control over the behavior of human cells, and how the state of each cell – its genetic make-up and biochemical state – affects its response to these ligands.

One current focus is on the cell death/survival decision induced by treating cancer cells with Tumor Necrosis Factor (TNF), a pro-inflammatory ligand. A fascinating aspect of the response to TNF is its variability: all cells express TNF receptor I, but in some TNF promotes survival or differentiation and in others, it promotes apoptosis. Even in clonal populations of cancer cells, some cells die, some survive. Because TNF induces a complex signaling network that includes pro-survival gene transcription by NF-kB, stress kinase and pro-apoptotic caspase activation, each cell must weigh many signals before committing to survival or apoptosis. Our goal is to identify the main determinants of the TNF-induced cellular response and to understand how cells “compute”, or integrate these many signals to make a life/death decision.

To investigate the TNF-induced life/death decision in human cancer cells, we use a combination of experimental and computational approaches. Our computational models formalize the known – or hypothesized – biochemistry of the TNFinduced signaling network and we use them to predict the effect of genetic or biochemical perturbations to the signaling network. Relying primarily on single-cell methods, we measure protein levels and signaling responses in treated cells in end-point or live-cell assays to test model predictions and the underlying hypotheses. The TNF-signaling network intersects with many others and we hope that by learning how cells compute the signals in this network, we can also predict cellular responses in many other contexts, including for example muscle cell differentiation and the epithelial-mesenchymal transition.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Gaudet, S.*, Spencer*, S.L., Chen, W.W. and Sorger, P.K. (2012) “Exploring the contextual sensitivity of factors that determine cell-to-cell variability in receptor-mediated apoptosis” PLoS Comput Biol, 8: e1002482. *equal contributors

Aldridge, B.B.*,
Gaudet, S.*, Lauffenburger, D.A. and Sorger, P.K. (2011) “Lyapunov exponents and phase diagrams reveal multi-factorial control over TRAIL-induced apoptosis” Mol Syst Biol, 7:553. *equal contributors

Spencer SL*,
Gaudet S*, Albeck JG, Burke JM, Sorger PK. Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature, 2009; 459: 428-32. *equal contributors

Albeck JG, Macbeath G, White FM, Sorger PK, Lauffenburger DA,
Gaudet S. Collecting and organizing systematic sets of protein data. Nat Rev Mol Cell Biol 2006; 7: 803-812. (Review)



© 2013 by the President and Fellows of Harvard College