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BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Joshua E. Elias Assistant Professor in Chemical and Systems Biology eRA COMMONS USER NAME JOSHELIAS EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Cornell University, Ithaca, NY Harvard Medical School, Boston, MA Harvard Medical School, Boston, MA DEGREE (if applicable) YEAR(s) B.A. 1995-1998 Biology Ph.D. 2000-2006 Cell Biology 2006-2009 Cell biology FIELD OF STUDY A. Personal Statement The combination of liquid chromatography and tandem mass spectrometry (LC-MS/MS) has emerged as the most robust technology available today for performing the in-depth protein identification, quantification and characterization experiments this project demands. Focusing this powerful technology towards the task of identifying new interacting proteins and post-translational modifications will require technical and computational expertise, and biological insight. My graduate and post-graduate work in each of these areas helped advance the nascent proteomics field to its current state: pioneering investigations of complex mixture separation (ref. 15) and multiple proteomics platforms (ref 10); methods for improved spectrum interpretation (refs 12,13), the standard-setting “target-decoy” searching strategy (refs 3,7) and an approach for automating peptide quantification (ref 6). We applied what we learned from these advances to tissue-specific comparisons of posttranslational modifications by phosphorylation (ref 1), with collaborators Denis Selkoe and Bruce Yankner at Harvard Medical School, investigations into regulatory processes central to Parkinson’s and Alzheimer’s diseases (refs 4,5,11), and with Peter Sicinski at the Dana Farber Cancer Institute, a tissue-specific assessment of proteins that interact with Cyclin D1 (ref 2). My lab is extending these accomplishments by pushing the limits of proteomic technologies and computational approaches. Our interests are primarily biology-driven; we are improving our technology so that we can more sensitively, accurately and comprehensively study dynamic protein systems as they relate age-related disorders including heart disease, cancer, and digestive diseases. B. Positions and Honors Positions and Employment 1998-2000 Research Associate, Millennium Pharmaceuticals, Cambridge, MA 1999 Scientific Consultant, Franklin Institute, Philadelphia, PA 2006-2009 Research Fellow in Cell Biology, Harvard Medical School, Boston, MA. Co-advisors: Steven Gygi, Peter Sicinski 2009-present Assistant professor in Chemical and Systems Biology, Stanford Medical School, Palo Alto, CA Other Experience and Professional Memberships 2001-present American Society of Mass Spectrometry (ASMS), Member 2010-present American Society for Biochemistry and Molecular Biology, Member 2010-present Molecular and Cellular Proteomics, Editorial board member C. Selected Peer-reviewed Publications 1. Huttlin, E.L.*, Jedrychowski, M.P.*, Elias, J.E.*, Goswami, T.*, Rad, R., Beausoleil, S.A., Villen, J., Haas, W., Sowa, M.E., Gygi, S.P. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-1189 (2010) [*equal contribution]. 2. Bienvenu, F., Jirawatnotai, S., Elias, J.E., Meyer, C.A., Mzeracka, K., Marson, A., Frampton, G.M., Cole, M.F., Odom, D.T., Odajima, J., Geng, Y., Zagozdzon, A., Jecrois, M., Young, R.A., Liu, X.S., Cepko, C.L., Gygi, S.P., Sicinski, P. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature 463, 374-378 (2010). 3. Elias, J.E. & Gygi, S.P. Target-decoy search strategy for mass spectrometry-based proteomics. Methods Mol Biol 604, 55-71 (2010). 4. Hemming, M.L., Elias, J.E., Gygi, S.P. & Selkoe, D.J. Identification of beta-secretase (BACE1) substrates using quantitative proteomics. PLoS One 4, e8477 (2009). 5. Hemming, M.L., Elias, J.E., Gygi, S.P. & Selkoe, D.J. Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biol. 6, 2314-2328 (2008). 6. Bakalarski, C.E., Elias, J.E., Villen, J., Haas, W., Gerber, S.A., Everley, P.A., Gygi, S.P. The impact of peptide abundance and dynamic range on stable-isotope-based quantitative proteomic analyses. J. Proteome Res. 7, 4756-4765 (2008). 7. Elias, J.E. & Gygi, S.P. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods 4, 207-214 (2007). 8. Gartner, C.A., Elias, J.E., Bakalarski, C.E. & Gygi, S.P. Catch-and-Release Reagents for Broadscale Quantitative Proteomics Analyses. J Proteome Res (2007). 9. Everley, P.A., Bakalarski, C.E., Elias, J.E., Waghorne, C.G., Beausoleil, S.A., Gerber, S.A., Faherty, B.K., Zetter, B.R. & Gygi, S.P. Enhanced analysis of metastatic prostate cancer using stable isotopes and high mass accuracy instrumentation. J Proteome Res 5, 1224-1231 (2006). 10. Elias, J.E., Haas, W., Faherty, B.K. & Gygi, S.P. Comparative evaluation of mass spectrometry platforms used in large-scale proteomics investigations. Nat Methods 2, 667-675 (2005). 11. Xu, J., Zhong, N., Wang, H., Elias, J.E., Kim, C.Y., Woldman, I., Pifl, C., Gygi, S.P., Geula, C. & Yankner, B.A. The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum Mol Genet 14, 1231-1241 (2005). 12. Gibbons, F.D., Elias, J.E., Gygi, S.P. & Roth, F.P. SILVER helps assign peptides to tandem mass spectra using intensity-based scoring. J Am Soc Mass Spectrom 15, 910-912 (2004). 13. Elias, J.E., Gibbons, F.D., King, O.D., Roth, F.P. & Gygi, S.P. Intensity-based protein identification by machine learning from a library of tandem mass spectra. Nat Biotechnol 22, 214-219 (2004). 14. Peng, J., Schwartz, D., Elias, J.E., Thoreen, C.C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D. & Gygi, S.P. A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 21, 921-926 (2003). 15. Peng, J., Elias, J.E., Thoreen, C.C., Licklider, L.J. & Gygi, S.P. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J Proteome Res 2, 43-50 (2003). D. Research Support Ongoing Research Support Damon Runyon New Innovator Award, DRR-13-11 (2011-2013,) Aim 1: Measure differential protein turnover rates between matched cancer cells that are resistant or sensitive to protein homeostasis inhibition. Aim 2: Evaluate the extent to which cancer cells overcome misfolded protein insults by asymmetric cell division. Completed Research Support None Pending Research Support None Overlap None