Photo of Suzanne Gaudet,

Suzanne Gaudet

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4269

Suzanne Gaudet

Dana-Farber Cancer Institute


  • Assistant Professor, Genetics, Harvard Medical School
  • Assistant Professor, Cancer Biology, Dana-Farber Cancer Institute


Research Abstract

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.

Our 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 1, 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 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 TNF-induced 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.


Powered by Harvard Catalyst
  • Mathew S, Thurber AE, Gaudet S. Finding the Optimal Tradeoffs. Cell Syst 2017; 4:149-151. PubMed
  • Lee RE, Qasaimeh MA, Xia X, Juncker D, Gaudet S. NF-κB signalling and cell fate decisions in response to a short pulse of tumour necrosis factor. Sci Rep 2016; 6:39519. PubMed
  • Gaudet S, Miller-Jensen K. Redefining Signaling Pathways with an Expanding Single-Cell Toolbox. Trends Biotechnol 2016. PubMed
  • Tan L, Wang J, Tanizaki J, Huang Z, Aref AR, Rusan M, Zhu SJ, Zhang Y, Ercan D, Liao RG, Capelletti M, Zhou W, Hur W, Kim N, Sim T, Gaudet S, Barbie DA, Yeh JR, Yun CH, Hammerman PS, Mohammadi M, Jänne PA, Gray NS. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A 2014; 111:E4869-77. PubMed
  • Hill SJ, Rolland T, Adelmant G, Xia X, Owen MS, Dricot A, Zack TI, Sahni N, Jacob Y, Hao T, McKinney KM, Clark AP, Reyon D, Tsai SQ, Joung JK, Beroukhim R, Marto JA, Vidal M, Gaudet S, Hill DE, Livingston DM. Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage. Genes Dev 2014; 28:1957-75. PubMed
  • Zhu Z, Aref AR, Cohoon TJ, Barbie TU, Imamura Y, Yang S, Moody SE, Shen RR, Schinzel AC, Thai TC, Reibel JB, Tamayo P, Godfrey JT, Qian ZR, Page AN, Maciag K, Chan EM, Silkworth W, Labowsky MT, Rozhansky L, Mesirov JP, Gillanders WE, Ogino S, Hacohen N, Gaudet S, Eck MJ, Engelman JA, Corcoran RB, Wong KK, Hahn WC, Barbie DA. Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. 2014; 4:452-65. PubMed
  • Lee RE, Walker SR, Savery K, Frank DA, Gaudet S. Fold change of nuclear NF-κB determines TNF-induced transcription in single cells. Mol Cell 2014; 53:867-79. PubMed
  • Xia X, Owen MS, Lee RE, Gaudet S. Cell-to-cell variability in cell death: can systems biology help us make sense of it all? Cell Death Dis 2014; 5:e1261. PubMed
  • Gaudet S, Spencer SL, Chen WW, Sorger PK. Exploring the contextual sensitivity of factors that determine cell-to-cell variability in receptor-mediated apoptosis. PLoS Comput. Biol. 2012; 8:e1002482. PubMed
  • Aldridge BB, Gaudet S, Lauffenburger DA, Sorger PK. Lyapunov exponents and phase diagrams reveal multi-factorial control over TRAIL-induced apoptosis. Mol Syst Biol 2011; 7:553. PubMed
  • Gaudet S, Langlois MJ, Lue RA, Rivard N, Viel A. The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring. BMC Cell Biol 2012; 12:55. PubMed
  • Gaudet S. Connecting cell fate decision networks in hematopoeisis from the outside in. Mol Syst Biol 2010; 6:418. PubMed
  • Kim KA, Spencer SL, Albeck JG, Burke JM, Sorger PK, Gaudet S, Kim do H. Systematic calibration of a cell signaling network model. BMC Bioinformatics 2010; 11:202. PubMed
  • 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. PubMed
  • 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; 7:803-12. PubMed
  • Janes KA, Gaudet S, Albeck JG, Nielsen UB, Lauffenburger DA, Sorger PK. The response of human epithelial cells to TNF involves an inducible autocrine cascade. Cell 2006; 124:1225-39. PubMed