Villén Lab

Cell Signaling and Proteomics


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The Villén Lab seeks to develop and apply novel experimental and computational technologies for global proteome characterization to answer fundamental questions in cell biology and disease.

Research



The Villen Lab seeks to develop and apply novel experimental and computational technologies for global proteome characterization to answer fundamental questions in cell biology and disease. We use quantitative mass spectrometry to measure dynamic changes in protein abundances, protein post-translational modification states, and to characterize interacting partners across multiple conditions.


We are particularly interested in studying protein phosphorylation as a general regulatory mechanism involved in a myriad of cellular functions. Two major questions we are trying to answer on a systems scale are: how phosphorylation is integrated into the multiple insults and responses to shape the proteome, and how signaling circuits evolved to accommodate proteome functional complexity. Some of the current projects in the lab in this area are:


  • Characterization of protein phosphorylation events: Collecting massive data sets to unravel structural, functional and evolutionary features of phosphorylation.
  • Oncogenic kinases and signaling pathways in breast cancer: Quantitative phosphoproteomics to understand signaling networks, and signatures in cancer onset.
  • Signaling and aging: We are studying the signaling mechanisms underlying lifespan extension under dietary restriction, or via inhibition of mTOR.

We also aim to understand how protein concentrations are balanced, regulated and altered through gene expression and degradation to accommodate multiple cellular functions. Specifically, we are studying:


  • Effects of protein phosphorylation in protein stability and degradation: Interplay of multiple post-translational modifications and effects in protein degradation.
  • Protein translation as a mechanism to regulate protein concentration: Studying the mechanisms of protein translation and monitoring protein synthesis using quantitative mass spectrometry.

Publications


Our lab

Swaney, D.L., Beltrao, P., Starita, L., Guo, A., Rush, J., Fields, S., Krogan, N.J., and Villen, J. (2013). Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation. Nature Methods 10, 676–682. PDF Supplementary_info RAW data

Edelman, W.C., Haas, K.M., Hsu, J.I., Lawrence, R.T., and Villen, J. (2014). A practical recipe to survey phosphoproteomes. Methods Mol. Biol. 1156, 389–405.

Lawrence, R.T., and Villen, J. (2014). Drafts of the human proteome. Nat. Biotechnol. 32, 752–753.

Martin-Perez, M., and Villen, J. (2015). Feasibility of protein turnover studies in prototroph S. cerevisiae strains. Anal. Chem. 87, 4008–4014.

Lawrence RT, Perez EM, Hernández D, Miller CP, Haas KM, Irie HY, Lee SI, Blau CA, Villén J. (2015). The proteomic landscape of triple-negative breast cancer. Cell Rep. 11, 630–644.

Swaney DL, Rodríguez-Mias RA, Villén J. (2015). Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover. EMBO Rep. 16,1131–1144.

Lawrence RT, Searle BC, Llovet A and Villén J. Plug and play analysis of the human phosphoproteome by targeted high-resolution mass spectrometry. Nature Methods (2016) Mar 28. doi: 10.1038/nmeth.3811 [Epub ahead of print].

Our collaborations

Helmlinger, D., Marguerat, S., Villen, J., Swaney, D.L., Gygi, S.P., Bähler, J., and Winston, F. (2011). Tra1 has specific regulatory roles, rather than global functions, within the SAGA co-activator complex. EMBO J. 30, 2843–2852.

Beltrao, P., Albanèse, V., Kenner, L.R., Swaney, D.L., Burlingame, A., Villen, J., Lim, W.A., Fraser, J.S., Frydman, J., and Krogan, N.J. (2012). Systematic functional prioritization of protein posttranslational modifications. Cell 150, 413–425.

Ranjitkar, P., Perera, B.G.K., Swaney, D.L., Hari, S.B., Larson, E.T., Krishnamurty, R., Merritt, E.A., Villen, J., and Maly, D.J. (2012). Affinity-based probes based on type II kinase inhibitors. J. Am. Chem. Soc. 134, 19017–19025.

Pruneda, J.N., Smith, F.D., Daurie, A., Swaney, D.L., Villen, J., Scott, J.D., Stadnyk, A.W., Le Trong, I., Stenkamp, R.E., Klevit, R.E., et al. (2014). E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis. EMBO J. 33, 437–449.

Eaton, J.M., Takkellapati, S., Lawrence, R.T., McQueeney, K.E., Boroda, S., Mullins, G.R., Sherwood, S.G., Finck, B.N., Villen, J., and Harris, T.E. (2014). Lipin 2 binds phosphatidic acid by the electrostatic-hydrogen bond switch mechanism independent of phosphorylation. J. Biol. Chem. 289, 18055-66

Chow, J.D.Y.*, Lawrence, R.T.*, Healy, M.E., Dominy, J.E., Liao, J.A., Breen, D.S., Byrne, F.L., Kenwood, B.M., Lackner, C., Okutsu, S., Mas, V.R., Caldwell, S.H., Tomsig, J.L., Cooney, G.J., Puigserver, P.B., Turner, N., James, D.E., Villén, J.#, and Hoehn, K.L.# (2014). Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylation. Mol. Metab. 3, 419–431. (*equal contribution; #co-corresponding)

Eichhorn, S.W., Guo, H., McGeary, S.E., Rodríguez-Mias, R.A., Shin, C., Baek, D., Hsu, S.-H., Ghoshal, K., Villen, J., and Bartel, D.P. (2014). mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol. Cell 56, 104–115.

Resources


We are providing tools and sharing data for some of our publications as web resources. Links are provided below:

People


Villén Lab, October 2015

Current lab members

  • Judit Villen (PI)
  • Miguel Martin (postdoc)
  • Ricard Rodriguez (research scientist)
  • William Edelman (GS graduate student)
  • Rob Lawrence (MCB graduate student)
  • Sam Entwisle (MCB graduate student)
  • Ariadna Llovet (software engineer)

Lab alumni

  • Josep Rubi (software engineer, 2010)
  • Zoi Villasana (MCB rotation, Summer 2011)
  • Pratistha Ranjitkar (postdoc, 2011)
  • Marissa Anderson (summer undergraduate 2011, U. New Mexico)
  • Lindsay Stanford (summer undergraduate 2012, Spelman College)
  • Andrei Chertov (postdoc, 2012)
  • Han-Yin Yang (GS rotation, Winter 2013)
  • Joanne Hsu (undergraduate student, 2011-2013)
  • Elizabeth Perez (summer undergraduate, 2013)
  • Kelsey Haas (undergraduate student & postbac, 2012-2014)
  • Oriol Quilez (visiting student, 2014)
  • Jason Ross (summer undergraduate, 2014)
  • Danielle Swaney (postdoc, 2010-2014)
  • Alex Corella (MCB rotation, Fall 2014)
  • Peter Mosen (visiting master student, 2015)
  • Brian Searle (GS rotation, Winter 2015)
  • Paige Haas (undergraduate student, 2015)
  • Daniel Hernandez (software engineer, 2012-2015)
  • Andrea Costa (visiting scientist, 2015)
  • Kelly Jin (MD3 rotation, Winter 2016)

About


The Villén lab started as part of the Genome Sciences Department at the University of Washington in July 2010.

Contact information

William H. Foege Hall, 3720 15th Ave NE
Seattle, WA 98105


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