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OMB No. 0925-0001/0002 (Rev. 02/04 Approved Through 02/29/2016) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Ofer Levy eRA COMMONS USER NAME (credential, e.g., agency login): leofoster POSITION TITLE: Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY Simon Fraser University, BC B.Sc. 04/1996 Biochemistry University of Toronto, ON Ph.D. Postdoctoral 04/2001 Biochemistry 11/2004 Proteomics University of Southern Denmark, Odense, Denmark Please refer to the Biographical Sketch sample in order to complete sections A, B, C, and D of the Biographical Sketch. A. Personal Statement My background in biochemistry, as well as molecular and cellular biology, combined with formal training in proteomics and analytical chemistry, allows me to bridge both sides of systems biology (the technology required for system-wide measurements and the interpretation of the biology). My laboratory’s current focus is on applying quantitative proteomics to understand many different areas of host-pathogen interactions, including the innate and adaptive responses. We have extensive experience in using a variety of in vitro and cell-based assays, as well as qualitative and quantitative mass spectrometry-based detection techniques, to characterize and quantify changes in protein expression, protein interactions and protein modifications in a variety of systems. One particular focus has been on identifying candidate antigens for vaccine development by characterizing the antigens presented on the surface of antigen-presenting cells challenged with pathogens. As a PI on the grants listed below, I administer the projects, including recruiting all personnel, obtaining biosafety and ethics approvals, and budget oversight. I collaborate locally, nationally and internationally with many researchers across diverse disciplines and collectively have produced multiple peer-reviewed PubMedindexed publications from each project. These projects have typically involved applying proteomics to characterize host-pathogen interactions, along the lines of my own group’s interests. The current application builds on several aspects of my prior work to characterize the host response to vaccination. As my publication record demonstrates, I can and will deliver on the research plans outlined here. Specific publications illustrating expertise in the proteomic side of systems biology include (my trainees are underlined): 1. Lubieniecka, J.M., F. Streijger, N. Stoynov, J. Liu, R. Mottus, T. Pfeifer, B.K. Kwon, J.R. Coorssen, L.J. Foster, T.A. Grigliatti and W. Tetzlaff. “Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.” PLOS ONE. 6.4 (2011): e19247. PMID 21559420. 2. Rogers, L.D., Y. Fang, N.F. Brown, S. Pelech and L.J. Foster. “Phosphoproteomic analysis of Salmonella-infected cells identifies key kinase regulators and SopB-dependent host phosphorylation events.” SCIENCE SIGNALING. 4.191 (2011): rs9. PMID 21934108. 3. Imami, K., A.P. Bhavsar, H. Yu, N.F. Brown, L.D. Rogers, B.B. Finlay and L.J. Foster. “Global impact of Salmonella pathogenicity island 2-secreted effectors on the host phosphoproteome.” MOLECULAR & CELLULAR PROTEOMICS. 12.6 (2013): 1632 – 1643. doi: 10.1074/mcp.M112.026161. PMID 23459991. 4. Kristensen, A.R., J. Gsponer and L.J. Foster. “Protein synthesis rate is the predominant regulator of protein expression during differentiation.” MOLECULAR SYSTEMS BIOLOGY. 9 (2013): 689. doi: 10.1038/msb.2013.47. PMID 24045637. B. Positions and Honors Positions and Employment 1996 - 2001 Doctoral candidate, Programme in Cell Biology, Hospital for Sick Children, Vancouver, Canada 2000 - 2004 Assistant Research Prof., Centre for Experimental BioInformatics, Uni. of Southern Denmark 2005 - 2010 Assistant Professor, Biochemistry & Molecular Biology, University of British Columbia, Canada 2010 - 2015 Associate Professor, Biochemistry & Molecular Biology, University of British Columbia, Canada 2013 - 2015 Director, Centre for High-Throughput Biology, University of British Columbia, Canada 2015 Associate Director, Michael Smith Laboratories, University of British Columbia, Canada 2015 Professor, Biochemistry & Molecular Biology, University of British Columbia, Canada Other Experience and Professional Memberships 2003 – Member, Human Proteome Organization (HUPO) 2005 – Member, Canadian Society for Biochemistry, Molecular and Cellular Biology (CSBMCB) 2006 – Member, American Society for Biochemistry and Molecular Biology (ASBMB) Honors 1996 – 2001 2002 – 2003 2007 – 2008 2009 2005 – 2010 2005 – 2015 2016 Doctoral Studentship, Visiting Lecturer Medical Research Council of Canada European Molecular Biology Organization Research Award Peter Wall Institute for Advanced Studies Early Career Scholar Early Career Faculty Research Award, Faculty of Medicine, UBC Michael Smith Foundation for Health Research Award Canada Research Chair in Quantitative Proteomics Killam Faculty Research Prize C. Contribution to Science My five most significant contributions to science are as follows: 1) Early in my career I focused on the burgeoning field of organelle proteomics and I was particularly focused on improving the quality of data that was being published in this area. For many years most researchers were only taking a qualitative approach in virtually all applications of proteomics. With my background in biochemistry and cell biology though, I advocated that we could do much more. My most highly cited publication (PNAS, 2003) was perhaps the seminal work in this area, but we have published many other studies showing that very highly accurate maps of subcellular structures can be measured and, with this accuracy, one can then start to explore functional systems biology of these compartments. (a) Rogers, L.D. and L.J. Foster. "The dynamic phagosome proteome and the contribution of the ER". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE U.S.A. 104.47 (2007): 18520 - 18525. PMID 18006660. (b) Zheng, Y.Z., K.B. Berg and L.J. Foster. “Mitochondria do not contain lipid rafts and lipid rafts do not contain mitochondrial proteins.” JOURNAL OF LIPID RESEARCH. 50.5 (May 2009): 988 - 998. PMID 19136664. (c) Foster, L.J., C.L. de Hoog, Y. Zhang, Y. Zhang, X. Xie, V.K. Mootha and M. Mann. "A mammalian organelle map by protein correlation profiling.” CELL. 125.1 (2006): 187 - 199. PMID 16615899. (d) Foster, L.J., C.L. de Hoog and M. Mann. "Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, U.S.A. 100.10 (2003): 5813 - 5818. PMID 12724530. 2) The area of my research with the most direct and immediate application to health practices is in the area of antigen presentation. From the early days of my independent career, I have worked with clinical collaborators to identify immunodominant antigens from Chlamydia trachomatis, the cause of chlamydiosis, a sexually transmitted bacterial infection. By applying a very stringent bioinformatic approach to the treatment of mass spectrometry data, we were able to achieve an extremely high ‘hit rate’ with the antigens we were discovering. Compared to a hit rate of 1% or less with reverse vaccinology approaches, we were able to accurately identify suitable subunit vaccine components with a success rate of 50 to 80%. This has led to a candidate vaccine that is currently in pre-clinical, nonhuman primate trials and that has advanced farther down the clinical development path than any previous Chlamydia vaccine. (a) Karunakaran, K.P., H. Yu, X. Jiang, Q.W.T. Chan, K.M. Moon, L.J. Foster and R.C. Brunham. “Outer membrane proteins preferentially load MHC class II peptides: implications for a Chlamydia trachomatis T cell vaccine.” VACCINE. 33.18 (2015): 2159 – 2166. doi: 10.1016/j.vaccine.2015.02.055. PMID 25738816. (b) b. Yu, H., K.P. Karunakaran, I. Kelly, C. Shen, X. Jiang, L.J. Foster and R.C. Brunham. “Immunization with live and dead Chlamydia muridarum induce different levels of protective immunity in a murine genital tract model: correlation with MHC class II peptide presentation and multifunctional Th1 cells.” JOURNAL OF IMMUNOLOGY. 186.6 (2011): 3615 – 3621. PMID 21296978 (c) Karunakaran, K.P., J. Rey-Ladino, N. Stoynov, K. Berg, C. Shen, X. Jiang, B. Gabel, H. Yu, L.J. Foster* and R.C. Brunham*. "Immunoproteomic discovery of novel T cell antigens from the obligate intracellular pathogen Chlamydia." JOURNAL OF IMMUNOLOGY. 180.4 (2008): 2459 - 2465. PMID 18250455. (d) Ferreira, R.B.R., Y. Valdez, B.K. Coombes, S. Subash, J.W. Gouw, E.M. Brown, Y. Li, G.A. Grassl, L.C.M. Antunes, N. Gill, M. Truong, R. Scholz, L. Reynolds, L. Krishnanc, A.A. Zaferc, N. Sal-Man, M.J. Lowden, S.D. Auweter, L.J. Foster and B.B. Finlay. “A highly effective component vaccine against non-typhoidal Salmonella infections.” MBIO. 6.5 (2015): pii: e01421-15. doi: 10.1128/mBio.01421-15. PMID 26396246. 3) The most recent area where we have started to have an impact is in the area of protein-protein interaction networks, or interactomes. For several years, this area has been dominated by brute-force approaches (e.g., yeast 2-hybrid, affinity-purification of thousands of baits followed by mass spectrometric identification of preys) but these methods have a high false positive rate and are so laborious that they cannot be replicated easily or used to test differential conditions. Recently, we have developed methods and associated informatics for applying the principle of protein correlation profiling to mapping interactomes. We use precise chromatographic co-elution to determine the composition of protein complexes in the cytosol of any cell type. On top of this, we are able to measure how all of the proteins altered its association with each complex in response to a stimuli. Our new method can probe the interactome to the same or greater depth and with equal or greater accuracy than the standard immunoprecipitation/mass spectrometry, yet using 99% less instrument and personnel time. This improvement in throughput is equivalent to the improvement in sequencing capacity that massively parallel sequencing has over Sanger sequencing of DNA. (a) Scott, N.E., L.M. Brown, A.R. Kristensen and L.J. Foster. “Development of a computational framework for the analysis of protein correlation profiling and spatial proteomics experiments.” JOURNAL OF PROTEOMICS. 2014. S1874-3919(14)00524-7. doi: 10.1016/j.jprot.2014.10.024. PMID 25464368. (b) Kristensen, A.R., J. Gsponer and L.J. Foster. “A high-throughput approach for measuring temporal changes in the interactome.” NATURE METHODS. 9.9 (2012): 907 – 909. doi: 10.1038/nmeth.2131. PMID 22863883. (c) Scott, N.E., L.D. Rogers, A. Prudova, N.F. Brown, N. Fortelny, C.M. Overall and L.J. Foster. “Interactome disassembly during apoptosis occurs independent of caspase cleavage.” MOLECULAR CELL. Under review. The URL to a full list of my published work as found on PubMed, appears below: http://www.ncbi.nlm.nih.gov/pubmed/?term=foster+lj D. Research Support Canada Foundation for Innovation Foster (PI) 9/1/13-6/31/16 Immune system polymorphism and Host/Pathogen Interactions An equipment grant for renewing mass spectrometry and other high-content infrastructure Role: PI (with 6 co-applicants) 221BEE Foster (PI) 10/1/15-9/30/19 Genome Canada/Genome BC Sustaining and securing Canada’s honey bees using ‘omic tools This project aims to use proteomics to identify molecular markers diagnostic of disease resistance in honey bees. Role: PI (with 7 co-applicants) MOP-77688 Foster (PI) 10/1/13-9/30/18 Canadian Institutes of Health Research Building a systems biology view of Salmonella-host interactions This grant is aimed at using proteomics to map the direct host binding partners of Salmonella effectors and the host proteins targeted by Salmonella ubiquitylating/deubiquitylated enzymes. Role: PI Discovery Grant 311654-11 Foster (PI) 4/1/11-3/31/16 Natural Sciences & Engineering Research Council Studying honey bee health in in vitro systems This grant is aimed at developing and using in vitro systems for studying host-pathogen interactions in honey bees. Role: PI Brain Canada Kwon (PI) 7/1/16-6/30/19 Biomarkers for Crossing the Translational Divide in Acute Spinal Cord Injury This grant is aimed at identifying proteomic and metabolomic signatures of CSF from acute spinal cord injury patients Role: Co-applicant (with 8 co-applicants) Brain Canada Vocadlo (PI) 7/1/16-6/30/19 Preclinical development of a disease modifying small molecule therapy for Alzheimer disease This grant is aimed at exploring the mechanism of action of a novel Alzheimer’s therapeutic. Role: Co-applicant (with 9 co-applicants) Completed Canada Foundation for Innovation Foster (PI) Leading Edge Fund Immune system polymorphism and host-pathogen interactions This was an equipment grant to renew proteomics infrastructure 9/22/11-12/30/14 107BEE Foster (PI) 4/1/11-12/31/14 Genome Canada/Genome BC Next-generation integrated pest management tools for beekeeping This project aims to use proteomics to identify molecular markers diagnostic of disease resistance in honey bees.