Program Director/Principal Investigator (Wolf-Yadlin, Alejandro): BIOGRAPHICAL SKETCH Provide the following information for the Senior/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 Alejandro Wolf-Yadlin POSITION TITLE Assistant Professor Department of Genome Sciences University of Washington eRA COMMONS USER NAME (credential, e.g., agency login) ayadlin EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Universidad de Chile. Santiago, Chile B.S 07/1999 Biotechnology Engineering Universidad de Chile. Santiago, Chile Engineering 04/2001 Biotechnology Engineering Universidad de Chile. Santiago, Chile M.S 04/2001 Chemical Engineering Massachusetts Institute of Technology. Cambridge, PHD 02/2007 Bioengineering MA Harvard University. Cambridge, MA Postdoc 06/2010 Systems Biology A. Personal Statement The overarching goal of our research program focuses on the study of cellular signaling networks, their relationship to gene expression and cellular phenotype. During my first year at UW I have been developing the framework to apply this approach to projects in basic cell biology as well as cancer biology and neurodegenerative and infectious diseases. More specifically, our laboratory focuses on the development and application of new proteomic based technologies to understand cellular signaling networks in the context of cellular homeostasis and disease. We use mass spectrometry to detect and quantify changes in protein expression, post-translational modifications and protein-protein and protein-DNA interactions over a wide range of biological conditions. In parallel, we have developed and are currently using high-throughput techniques to monitor gene expression and cellular phenotype under the same biological conditions we use for proteomics analysis. Finally, we integrate these datasets using and/or developing computational tools to determine the structure and dynamic behavior of signaling and gene-expression networks to reveal causal relationships between our distinct classes of measurements. Although, we are interested in various types of post-translational modifications, currently our main focus is protein phosphorylation. Phosphorylation is one of the most common regulatory mechanisms in the cell. It plays a role in determining various cellular outcomes including proliferation, migration, gene expression, apoptosis, cellular size/shape and differentiation. The question we aim to answer is how dynamic changes in phosphorylation regulate these outcomes and how the information encoded by these modifications is integrated into a single coherent biological response. We are doing this by attempting to find causal relationships between protein phosphorylation, protein-protein interactions, gene expression and cell phenotype. We hope that our efforts will provide a better understanding of the cell and highlight network features that correlate or cause changes in gene expression and/or cell behavior in disease states. B. Positions and Honors Positions and Employment 2007-2010 Postdoctoral Fellow, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 2011Assistant Professor, Department of Genome Science, University of Washington, Seattle, WA Other Experience and Professional Memberships 2011Member of STRIDE Center for Systems & Translational Research on Infectious Disease, University of Washington 2011Member of Proteomic Resource, University of Washington 2011Member of American Society of Mass Spectrometry Honors 2000 2001-2002 European Community alpha scholarship for graduate students Du Pont Fellowship for first year graduate students at MIT PHS 398/2590 (Rev. 06/09) Page 1 Biographical Sketch Format Page Program Director/Principal Investigator (Wolf-Yadlin, Alejandro): 2005 2006 2009 2010 2012 2012 2013 Best Poster award GTCbio 2nd International Conference on Tumor Progression & Therapeutic Resistance Daniel K. Ludwig Fellowship recipient for cancer research Awarded Best Poster at System Biology for Human Disease Conference Invited lecturer: “Lecture Series on Proteomics” at Cold Spring Harbor Laboratory Invited reviewer for SkTech Research Center Development Proposals. The Skolkovo Institute of Science and Technology (SkTech) is a new graduate university outside of Moscow, Russia Invited lecturer: “Lecture Series on Proteomics” at Cold Spring Harbor Laboratory Invited reviewer for SkTech Research Center Development Proposals. The Skolkovo Institute of Science and Technology (SkTech) is a new graduate university outside of Moscow, Russia C. Selected Peer-reviewed Publications (Selected from 10 peer-reviewed publications) Most relevant to the current application 1. * Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM. “ Time-resolved mass spectrometry of tyrosine phosphorylation sites in the EGF receptor signaling network reveals dynamic modules”. Mol Cell Proteomics. 2005; 4(9):1240-50. Epub 2005 Jun 11. 2. Wolf-Yadlin A, Kumar N, Zhang Y, Hautaniemi S, Zaman M, Kim HD, Grantcharova V, Lauffenburger DA, White FM. “Effects of HER2 overexpression on cell signaling networks governing proliferation and migration”. Mol Syst Biol. 2006; 2:54. Epub 2006 Oct 3. 3. Kumar N, Wolf-Yadlin A, White FM, Lauffenburger DA. “Modeling HER2 Effects on Cell Behavior from Mass Spectrometry Phosphotyrosine Data”. PLoS Comput Biol. 2007; 3(1):e4. Epub 2006 Nov 21. 4. * Zhang Y, Wolf-Yadlin A, White FM. “Quantitative Proteomic Analysis of Phosphotyrosine-Mediated Cellular Signaling Networks”. Methods Mol Biol. 2007; 359(14):203-212. 5. Wolf-Yadlin A, Hautaniemi S, Lauffenburger DA, White FM. “Multiple Reaction Monitoring for Robust Quantitative Proteomic Analysis of Cellular Signaling Networks”. Proc Natl Acad Sci U S A. 2007; 104(14):5860-5. Epub 2007 Mar 26. 6. Navare A, Sova P, Purdy DE, Weiss JM, Wolf-Yadlin A, Korth MJ, Chang ST, Proll SC, Krasnoselsky AL, Palermo RE, Katze MG. “Quantitative Proteomic Analysis of HIV-1 Infected CD4+ T Cells Reveals an Early Host Response in Important Biological Pathways: Protein Synthesis, Cell Proliferation, and T-cell Activation”. Virology. 2012; 429(1):3746. 7. Dai X, James RG, Habib T, Singh S, Jackson S, Khim S, Moon RT, Liggitt D, Wolf-Yadlin A, Buckner J, and Rawlings D. “The PTPN22 risk variant promotes systemic autoimmunity by altering lymphocyte selection and activation”. Accepted by Journal of Clinical Immunology. Reference 66963-RG-RV-3. 8. Moore KE, Carlson SM, Cheung P, Chua KF, Wolf-Yadlin A, Gozani O. “Engineering a Natural Affinity Reagent for Detection and Proteomic Analysis of Lysine Methylation”. Accepted by Molecular Cell. Reference D-12-01894R2. 9. James RG, Bosch KA, Yang PT, Robin NC, Toroni RA, Kulikauskas RM, Biechele TL, Berndt JD, von Haller PD, Eng J, Wolf-Yadlin A, Chien AJ, and Moon RT. "Protein Kinase PKN1 represses Wnt/ß-catenin signaling in human melanoma cells”. Submitted. 10. Wagner JP*, Wolf-Yadlin A*, Sevecka M, Grenier JK, Root DE, Lauffenburger DA, and MacBeath G. “Receptor Tyrosine Kinases Fall Into Distinct Classes Based on Their Inferred Signaling Networks”. Submitted. * In all papers marked with an * Wolf-Yadlin A is co-first author. Additional recent publications of importance to the field (in chronological order) 1. Gordus A, Krall JA, Beyer EM, Kaushansky A, Wolf-Yadlin A, Sevecka M, Chang BH, Rush J, MacBeath G. “Linear combinations of docking affinities explain quantitative differences in RTK signaling”. Mol Syst Biol. 2009; 5:235. Epub 2009 Jan 20. 2. Wolf-Yadlin A, Sevecka M, MacBeath, G. “Dissecting Protein Function and Signaling Using Protein Microarrays”. Curr. Opin. Chem. Biol. 2009; 13(4):398-405. Epub 2009 Aug 5. 3. Locasale JW, Wolf-Yadlin A,“Maximum entropy reconstructions of dynamic signaling networks from quantitative proteomics data”. PLoS One. 2009 Aug 26; 4(8):e6522. 4. * Sevecka M, Wolf-Yadlin A, MacBeath, G “Lysate Microarrays Enable High-throughput, Quantitative Investigations of Cellular Signaling”. Mol Cell Proteomics. 2011 Apr; 10(4):M110.005363. Epub 2011 Feb 4. PHS 398/2590 (Rev. 06/09) Page 2 Biographical Sketch Format Page Program Director/Principal Investigator (Wolf-Yadlin, Alejandro): D. Research Support Startup Funds Genome Sciences University of Washington NIH 1DP2OD017358-01, pending Mallinckrodt Foundation Grant 201302 deadline, pending Role: PI PHS 398/2590 (Rev. 06/09) Page 3 Biographical Sketch Format Page