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Transcript
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