Download D. Research Support

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.