Leonard Foster

Contact Information
Michael Smith Laboratories
University of British Columbia
301-2185 Health Sciences Mall
Vancouver, British Columbia
Canada V6T1Z4
Tel 1-604-822-8311
Fax 1-604-822-2114
foster@chibi.ubc.ca
Lab Website: http://www.chibi.ubc.ca/faculty/foster/labhome

Current Positions

  • Associate Professor, Department of Biochemistry & Molecular Biology

Research Interests

Host-pathogen interactions:
Mammalian-bacterial, honey bee-bacteria, honey bee-mites, honey bee-viruses.

Our lab is focused on quantitative proteomics using stable isotope labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to study biological systems. We cover a wide range of topics including pathogen invasion, infection, protein localization, and mapping protein interactions.

Mass spectrometry-based proteomics:
In order to understand how a complex system works it is extremely useful to know the identities of as many of the components of the system as possible. Commercially available mass spectrometers and database search tools have advanced to the point where experienced laboratories can routinely and reliably identify hundreds or thousands of proteins in exceedingly complex mixtures (i.e. an organelle preparation) using nanoflow high performance liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Typically, complex protein samples are reduced to peptides by highly specific enzymatic digestion (e.g. trypsin cleavage carboxy-terminal of Arg or Lys). The peptides are then resolved by extremely high-resolution reversed-phase chromatography and eluted/ionized directly into a mass spectrometer (MS). The MS, operating in an information-dependent mode, selects and isolates any peptide ions observed and subjects them to tandem mass spectrometry. The observed mass/charge ratio of the peptide and its fragmentation pattern are then used to scan comprehensive protein sequence libraries (e.g. for a human liver sample the data would be searched against the Homo sapiens library) to find the best theoretical match and the peptides are compiled to arrive at a ‘protein hit list’.

In the past few years we have witnessed great advances in methodologies for applying mass spectrometry-based proteomics to answer biologically relevant questions. Some of the most powerful of these methods involve the use of stable isotopes to incorporate a quantitative dimension into the experiment. Thus far, however, quantitative proteomics has yet to be widely applied in mainstream biology. Our group is interested in a multidisciplinary approach to relevant cell biological problems. We develop and apply quantitative proteomic methods to questions involving organelles and how the composition of these compartments change when antagonized. Additionally, we are involved in several projects involving host-pathogen interactions. The knowledge gained from proteomic experiments is then used to direct more in-depth biochemical, bioinformatic and cell biological analysis of the system in order to validate the proteomic results. We have an LTQ-OrbitrapXL and an LTQ-FT from ThermoFisher and an 6520 QTOF and 6430 QQQ from Agilent Technologies. In addition, we have our own 96-well peptide synthesizer for making synthetic standards and a variety of up-stream fractionation methods for enriching specific types of proteins or reducing sample complexity prior to LC-MS/MS.

Current Projects

  • Mapping signaling pathways downstream of and disrupted by Salmonella invasion
  • Finding host targets of effector proteins secreted from pathogenic bacteria
  • Exploring how membrane domains (phagosomes, lipid rafts) change during Salmonella invasion
  • Mapping protein interaction networks using novel, more efficient methods
  • Identifying biomarkers of disease resistance in honey bees
  • Identifying the components of royal jelly required for queen differentiation in honey bees

Selected Publication

  1. Bhavsar AP, Brown NF, Stoepel J, Wiermer M, Martin DD, Hsu KJ, Imami K, Ross CJ, Hayden MR, Foster LJ, Li X, Hieter P, Finlay BB. The Salmonella Type III Effector SspH2 Specifically Exploits the NLR Co-chaperone Activity of SGT1 to Subvert Immunity. PLoS Pathog. 2013 Jul;9(7):e1003518.
  2. Borchers CH, Kast J, Foster LJ, Siu KW, Overall CM, Binkowski TA, Hildebrand WH, Scherer A, Mansoor M, Keown PA; for the Human Proteome Organization Chromosome 6 Consortium. The Human Proteome Organization Chromosome 6 Consortium: Integrating chromosome-centric and biology/disease driven strategies. J Proteomics. 2013 Aug 8.
  3. Chan QW, Chan MY, Logan M, Fang Y, Higo H, Foster LJ. Honey bee protein atlas at organ-level resolution. Genome Res. 2013 Jul 22.
  4. Kristensen AR, Foster LJ. High throughput strategies for probing the different organizational levels of protein interaction networks. Mol Biosyst. 2013 Jul 30;9(9):2201-12.
  5. Imami K, Bhavsar AP, Yu H, Brown NF, Rogers LD, Finlay BB, Foster LJ. Global impact of Salmonella pathogenicity island 2-secreted effectors on the host phosphoproteome.  Mol Cell Proteomics. 2013 Jun;12(6):1632-43.
  6. Chen VC, Kristensen AR, Foster LJ, Naus CC. Association of Connexin43 with E3 Ubiquitin Ligase TRIM21 Reveals a Mechanism for Gap Junction Phosphodegron Control. J Proteome Res. 2012 Dec 7;11(12):6134-46.
  7. Parker R, Guarna MM, Melathopoulos AP, Moon KM, White R, Huxter E, Pernal SF, Foster LJ. Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera). Genome Biol. 2012 Jun 29;13(9):R81.
  8. Somasekharan SP, Stoynov N, Rotblat B, Leprivier G, Galpin JD, Ahern CA, Foster LJ, Sorensen PH. Identification and quantification of newly synthesized proteins translationally regulated by YB-1 using a novel Click-SILAC approach. J Proteomics. 2012 Dec 21;77:e1-e10
  9. Foster LJ. Introduction to Special Issue on phosphoproteomics. Semin Cell Dev Biol. 2012 Oct;23(8):835.
  10. Kristensen AR, Gsponer J, Foster LJ. A high-throughput approach for measuring temporal changes in the interactome. Nat Methods. 2012 Sep;9(9):907-9.
  11. Boscher C, Zheng YZ, Lakshminarayan R, Johannes L, Dennis JW, Foster LJ, Nabi IR.  Galectin-3 protein regulates mobility of N-cadherin and GM1 ganglioside at cell-cell junctions of mammary carcinoma cells. J Biol Chem. 2012 Sep 21;287(39):32940-52.
  12. Prehna G, Li Y, Stoynov N, Okon M, Vuckovic M, McIntosh LP, Foster LJ, Finlay BB, Strynadka NC. The zinc regulated antivirulence pathway of Salmonella is a multiprotein immunoglobulin adhesion system. J Biol Chem. 2012 Sep 21;287(39):32324-37.
  13. Gagné JP, Pic E, Isabelle M, Krietsch J, Ethier C, Paquet E, Kelly I, Boutin M, Moon KM, Foster LJ, Poirier GG. Quantitative proteomics profiling of the poly(ADP-ribose)-related response to genotoxic stress. Nucleic Acids Res. 2012 Sep;40(16):7788-805.
  14. Deng W, Yu HB, de Hoog CL, Stoynov N, Li Y, Foster LJ, Finlay BB.Quantitative proteomic analysis of type III secretome of enteropathogenic Escherichia coli reveals an expanded effector repertoire for attaching/effacing bacterial pathogens. Mol Cell Proteomics. 2012 Sep;11(9):692-709.
  15. Sal-Man N, Biemans-Oldehinkel E, Sharon D, Croxen MA, Scholz R, Foster LJ, Finlay BB. EscA is a crucial component of the type III secretion system of enteropathogenic Escherichia coli. J Bacteriol. 2012 Jun;194(11):2819-28.
  16. Lambertz U, Silverman JM, Nandan D, McMaster WR, Clos J, Foster LJ, Reiner NE. Secreted virulence factors and immune evasion in visceral leishmaniasis. J Leukoc Biol. 2012 Jun;91(6):887-99.
  17. Chen VC, Gouw JW, Naus CC, Foster LJ. Connexin multi-site phosphorylation: Mass spectrometry-based proteomics fills the gap. Biochim Biophys Acta. 2013 Jan;1828(1):23-34.
  18. Ruzzini AC, Ghosh S, Horsman GP, Foster LJ, Bolin JT, Eltis LD. Identification of an acyl-enzyme intermediate in a meta-cleavage product hydrolase reveals the versatility of the catalytic triad. J Am Chem Soc. 2012 Feb 17. [Epub ahead of print]
  19. Ren Q, Wang QS, Firth AE, Chan MM, Gouw JW, Guarna MM, Foster LJ, Atkins JF, Jan E Alternative reading frame selection mediated by a tRNA-like domain of an internal ribosome entry site. Ren Q, Wang QS, Firth AE, Chan MM, Gouw JW, Guarna MM, Foster LJ, Atkins JF, Jan E. Proc Natl Acad Sci U S A. 2012 Jan 13. [Epub ahead of print]
  20. Zhang XX, Chan CS, Bao H, Fang Y, Foster LJ, Duong F. Nanodiscs and SILAC-Based Mass Spectrometry to Identify a Membrane Protein Interactome. J Proteome Res. 2012 Feb 3;11(2):1454-9.
  21. Axerio-Cilies P, See RH, Zoraghi R, Worral L, Lian T, Stoynov N, Jiang J, Kaur S, Jackson L, Gong H, Swayze R, Amandoron E, Kumar NS, Moreau A, Hsing M, Strynadka NC, McMaster WR, Finlay BB, Foster LJ, Young RN, Reiner NE, Cherkasov A. Cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase. ACS Chem Biol. 2012 Feb 17;7(2):350-9.
  22. Ament SA, Chan QW, Wheeler MM, Nixon SE, Johnson SP, Rodriguez-Zas SL, Foster LJ, Robinson GE. Mechanisms of stable lipid loss in a social insect. J Exp Biol. 2011 Nov 15;214(Pt 22):3808-21.
  23. Chan QW, Mutti NS, Foster LJ, Kocher SD, Amdam GV, Wolschin F. The worker honeybee fat body proteome is extensively remodeled preceding a major life-history transition. PLoS One. 2011;6(9):e24794.
  24. Rogers LD, Brown NF, Fang Y, Pelech S, Foster LJ. Phosphoproteomic analysis of Salmonella-infected cells identifies key kinase regulators and SopB-dependent host phosphorylation events. Sci Signal. 2011 Sep 20;4(191):rs9.
  25. Chan QW, Cornman RS, Birol I, Liao NY, Chan SK, Docking TR, Jackman SD, Taylor GA, Jones SJ, de Graaf DC, Evans JD, Foster LJ. Updated genome assembly and annotation of Paenibacillus larvae, the agent of American foulbrood disease of honey bees. BMC Genomics. 2011 Sep 16;12:450.
  26. Shames SR, Bhavsar AP, Croxen MA, Law RJ, Mak SH, Deng W, Li Y, Bidshari R, de Hoog CL, Foster LJ, Finlay BB. The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300. Cell Microbiol. 2011 Oct;13(10):1542-57.
  27. Biemans-Oldehinkel E, Sal-Man N, Deng W, Foster LJ, Finlay BB. Quantitative proteomic analysis reveals formation of an EscL-EscQ-EscN type III complex in enteropathogenic Escherichia coli. J Bacteriol. 2011 Oct;193(19):5514-9.
  28. Zheng YZ, Boscher C, Inder KL, Fairbank M, Loo D, Hill MM, Nabi IR, Foster LJ. Differential impact of caveolae and caveolin-1 scaffolds on the membrane raft proteome. Mol Cell Proteomics. 2011 Oct;10(10):M110.007146.
  29. Chan QW, Parker R, Sun Z, Deutsch EW, Foster LJ. A honey bee (Apis mellifera L.) PeptideAtlas crossing castes and tissues. BMC Genomics. 2011 Jun 3;12:290.
  30. Auweter SD, Bhavsar AP, de Hoog CL, Li Y, Chan YA, van der Heijden J, Lowden MJ, Coombes BK, Rogers LD, Stoynov N, Foster LJ, Finlay BB. Quantitative mass spectrometry catalogues Salmonella pathogenicity island-2 effectors and identifies their cognate host binding partners. J Biol Chem. 2011 Jul 8;286(27):24023-35.
  31. Lubieniecka JM, Streijger F, Lee JH, Stoynov N, Liu J, Mottus R, Pfeifer T, Kwon BK, Coorssen JR, Foster LJ, Grigliatti TA, Tetzlaff W. Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats. PLoS One. 2011 Apr 29;6(4):e19247.

Education

  • Postdoctoral (Proteomics), University of Southern Denmark, Denmark, 2004
  • Ph.D. (Biochemistry), University of Toronto, Canada, 2001
  • B.Sc. (Biochemistry), Simon Fraser University, Canada, 1996

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