Research Interests

Our research relies to a large extent on the application of protein chemistry and molecular biology methods, which are used in combination with high resolution NMR spectroscopy. This combined experimental approach provides unique capabilities to study protein and peptide structures as well as their functional properties (metal ion and ligand binding properties, flexibility, membrane binding, etc.). In addition we often make use of molecular dynamics calculations and other biophysical approaches in our research (e.g. fluorescence and circular dichroism spectroscopy, microcalorimetry and mass spectrometry). Our attention is presently focused on a number of different proteins and peptides; moreover we have recently initiated a new metabolomics research program in Calgary.
   
Calcium-binding regulatory proteins are studied through site-directed mutagenesis, enzymatic assays, spectroscopic studies and NMR structure determination. Together these experimental techniques provide very detailed information about protein structure, their metal ion binding sites, and they can define the interaction surfaces for target protein binding. Our work centers on the regulatory calcium binding protein calmodulin and structurally related calcium-binding proteins, such as calcium-dependent protein kinases, caldendrin and the calcium-integrin binding proteins. At the moment we are studying mammalian calcium-binding proteins that play a role in the innate immune response and in brain metabolism. Moreover calcium-regulatory proteins that play a role in the plant stress response are also under study.
   
Bacterial iron uptake is essential for the survival of these microorganisms and consequently the proteins involved in this process are potential targets for the design of novel classes of antibiotics. We have been interested for a long time in proteins that mediate Fe (III) uptake and transport. In the early 90s we developed novel NMR techniques to directly study the binding of metal ions to mammalian Fe (III) transport proteins, such as transferrin and lactoferrin. Currently our interest is primarily focused on bacterial proteins that mediate iron uptake. For example, ferric siderophore binding proteins are characterized by biophysical and structural methods. Furthermore we actively study the transmembrane proteins TonB and ExbD that are involved in the energy transduction pathways that are required for the uptake of ferric iron complexes into the periplasm. More recently we have also initiated studies of the proteins involved in Fe (II) uptake by bacteria.
    
Antimicrobial peptides form an integral part of the innate immune response of humans and many other organisms. We are particularly interested in several tryptophan-rich peptides found in neutrophils or in digests of regular food proteins. Our work is aimed at elucidating the mechanism of action of host defense peptides and proteins. Our studies rely on NMR structure determination of membrane-bound peptides, which are analyzed in combination with microcalorimetry and membrane leakage studies. Recently we have also become involved in studies of structurally unrelated human antimicrobial peptides, such as beta-defensins and hepcidin, which have additional chemokine-like activities or act as iron-regulatory peptide hormones.
   
Metabolomics is an emerging area of NMR spectroscopy and mass spectrometry research, where the full complement of metabolites that is present in a specific biological compartment is determined. By quantitatively analyzing the changes that occur in the metabolite profiles in serum, urine or other biofluid samples obtained from patients, it is thought that some diseases, such as cancer or infectious diseases, might be detected earlier or better managed.  Apart from the potential clinical applications of metabolomics research it also provides a powerful tool to study drug metabolism in plants, compare antibiotic-resistant and -sensitive microorganisms or develop improved microbiological strains for biotechnology applications. Finally, these new technologies, which are still being developed further, can also be used to study the effects of exercise, diet and nutritional suppliments (e.g. vitamins) on the overall health in animal models and possibly in humans.

Courses Taught

Graduate Students

Awards

2001 - AHFMR Scientist Renewal (2001-2006)
2003 - Immigrant of Distinction Award, in recognition of outstanding professional accomplishments (Calgary Immigrant Society)
2004 - Outstanding Achievements in Supervision Award, Faculty of Graduate Studies Univ. of Calgary
2005 - Killam Resident Fellowship, University of Calgary
2006 - AHFMR Scientist Renewal (2006-2013)
2006 - Finalist - Outstanding leadership in Science ASTech Awards
2009 - Roche Diagnostics Award from the Canadian Society for Biochemistry, Molecular and Cell Biology
2011 - Lance Armstrong Chair in Molecular Cancer Epidemiology

Selected publications

Protein and Peptide Research

2012

Rekdal, O., Haug, B.E., Kalaaji, M., Hunter, H.N., Lindin, I, Israelsson, I., Solstad, T., Yang, N., Brandt, M., Mantizilas, D. and Vogel, H.J. (2012) "The relative spatial positions of tryptophans and cationic residues in helical membrane-active peptides determines their cytotoxicity" J. Biol. Chem. 287: 233-244.

Huang, H. and Vogel, H.J. (2012) "Purification and istope-labeling of calcium- and integrin-binding protein 1 for structural and functional NMR studies" Meth. Mol. Biol. (Ed. C. Heizmann; in press)

Haney, E.F., Nazmi, K., Bolscher, J.G.M. and Vogel, H.J. (2012) "Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin" Biochem. Biophys. Acta – Biomembranes 1818: 762-775.

Huang, H. and Vogel, H.J. (2012) "Structural basis for the activation of platelet integrin alphaIIb-beta3 by the calcium- and integrin-binding protein 1" J. Am. Chem. Soc. (in press)

2011

Nguyen, L.T., Haney E. F. and Vogel, H.J. (2011) “The expanding scope of antimicrobial peptide structures and their modes of action”  Trends Biotechnol. 29: 464-472.

Huang, H., Ishida, H., Yamniuk, A.P. and Vogel, H.J. (2011) “The solution structures of Ca2+-CIB1 and Mg2+-CIB1 and their interactions with the platelet integin alpha IIb cytoplasmic domain” J. Biol. Chem. 286: 17181-17192.

Gifford, J., Ishida, H. and Vogel, H.J. (2011)  “Fast methionine-based solution structure determination of calcium calmodulin complexes”  J. Biomol. NMR 50: 71-81.

Nguyen, L.T., de Boer, L., Zaat, S.A.J. and Vogel, H.J. (2011)  “Investigating the cationic side chains of the antimicrobial peptide tritipticin: hydrogen-bonding properties govern its membrane disruptive activities”  Biochem. Biophys. Acta-Biomembranes 1808: 2297-2303.

Saponja, J.A. and Vogel, H.J.  (2011)  “Quadrupolar central transition and carbon-13 NMR competition studies of metal ion binding to ovotransferrin”  Can. J. Chem. 89: 779-788.

Nguyen, L., Chau, J.K., Zaat, S.A. and Vogel, H.J. (2011) “Cyclic tritrpticin analogs with distinct biological activities”  Probiotics Antimicrob Proteins 3: 132-143.

Bolscher, J.G.M., Oudhoff, M.J., Nazmi, J.M., Guimaraes, C.P., Haney, E.F., Garcia-Vallejo, J.J., Vogel, H.J., van‘t Hof, W., Ploegh, H.L. and Veerman, E.C. (2011)  “Sortase A as a tool for high yield histatin cyclization”  Faseb J. 25: 2650-2658.

Nguyen, L.T., Kwakman, P.H.S., Chan, D.I., de Boer, L., Zaat, S.A. and Vogel, H.J. (2011) “Profiling platelet antimicrobial chemokines: NMR backbone dynamics studies of the platelet chemokines NAP-2 and TC-1”  Antimicrob. Agents Chemother. 55: 2074-2083.

Krewulak, K.D. and Vogel, H.J. (2011)  “TonB or not TonB, is that the question?”  Biochem. Cell Biol. 89: 87-97.

Chu, B.C. and Vogel, H.J. (2011)  “A structural and functional analysis of type III periplasmic and substrate binding proteins: their role in bacterial siderophore and heme transport”  Biol. Chem. 392: 39-52.

2010

Ishida H. and Vogel H.J. (2010) “The solution structure of a plant calmodulin and the CaM-binding domain of the vacuolar calcium-ATPase BCA1 reveals a new binding and activation mechanism." J. Biol. Chem. 285: 38502-38510.

Nguyen L.T., Chau J.K., Perry N.A., de Boer L., Zaat S.A.J. and Vogel H.J. (2010) “Serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs.” PLoS One 5(9): e12684.

Chan D.I. and Vogel H.J. (2010) “Current understanding of fatty acid biosynthesis and the acyl carrier protein.” Biochem J. 430: 1-19.

Chan D.I., Chu B.C., Lau C.K., Hunter H.N., Byers D.M. and Vogel H.J. (2010) “NMR solution structure and biophysical characterization of Vibrio harveyi acyl carrier protein A75H; effects of divalent metal ions.” J Biol Chem. 285: 30558-30566.

Ulke-Lemée A., Ishida H., Borman M.A., Valderrama A., Vogel H.J., and Macdonald J.A.(2010) “Tropomyosin-binding properties of the CHASM protein are dependent upon its calponin homology domain.” FEBS Lett. 584: 3311-3316.

Chu B.C., Garcia-Herrero A., Johanson T.H., Krewulak K.D., Lau C.K., Peacock R.S., Slavinskaya Z. and Vogel, H.J. (2010) “Siderophore uptake in bacteria and the battle for iron with the host; a bird's eye view.” Biometals 23: 601-11.

Chan, D.I., Tieleman, D.P. and Vogel, H.J.  (2010) “Molecular dynamics studies of beta-ketoacyl, beta-hydroxyacyl and trans-2-enoyl Acyl Carrier Protein of Escherichia coli”  Biochemistry 49: 2860-2868.

Otten, R., Chu, B., Krewulak, K.D., Vogel, H.J.  and Mulder, F.A.A. (2010) “Comprehensive and cost-effective NMR spectroscopy of methyl groups in large proteins”  J. Am. Chem. Soc. 132: 2952-2960.

Nguyen L.T., Chan, I.D., Boszhard, L., Zaat, S.A.J. and Vogel, H.J.  (2010) “Structures and antimicrobial activities of chemokine-derived carboxy-terminal helical peptides” Biochem. Biophys. Acta - Biomembranes 1798: 1062-1072.

Huang, H., Ishida, H. and Vogel, H.J. (2010)  “The solution structure of the Mg2+ - form of soybean calmodulin isoform 4 reveals unique features of plant calmodulins in resting cells”  Protein Sci. 19: 475-485.

Haney, E.F., Nathoo, S., Vogel, H.J. and Prenner, E.J.  (2010)  “Induction of non-lamellar lipid phases by antimicrobial peptides: a possible link to mode of action”  Chem. Phys. Lipids. 163: 82-93.

2009

Ishida H., Rainaldi M., Vogel H.J. (2009) "Structural studies of soybean calmodulin isoform 4 bound to the calmodulin-binding domain of tobacco mitogen-activated protein kinase phosphatase-1 provide insights into a sequential target binding mode" J Biol Chem. 284: 28292-305.

Llamas M.A., van der Sar A., Chu B.C., Sparrius M., Vogel H.J., Bitter W. "A Novel extracytoplasmic function (ECF) sigma factor regulates virulence in Pseudomonas aeruginosa." PLoS Pathog. (2009):e1000572.

Yamniuk A.P., Burling, H. and Vogel H.J. (2009) "Thermodynamic characterization of the interactions between the immunoregulatory proteins osteopontin and lactoferrin." Mol. Immunol. 46: 2395-2402.

Haney, E.F. and Vogel, H.J. (2009) "NMR of antimicrobial peptides." Annu. Reports NMR Spectroscopy 65:1-51.

Yamniuk, A.P., Ishida, H., Lippert, D., and Vogel, H.J. (2009).  “Thermodynamic effects of non-coded and coded methionine-substitutions in calmodulin”. Biophys. J. 96:1495-1507.

Haney, E.F., Nazmi, K., Lau, F., Bolscher, J.G.M. and Vogel, H.J. (2009).  “Novel lactoferrampin antimicrobial peptides derived from human lactoferrin”.  Biochimie 91: 141-154.

Pushie, M.J. and Vogel, H.J. (2009).  “A potential mechanism for Cu2+-reduction, beta-cleavage and beta-sheet initiation within the N-terminal domain of the prion protein:  Insights from Density Functional Theory and Molecular Dynamics Calculations”.  J. Toxicol. Environm. Health. 72:1040-1059

Lopez, C.S., Peacock, R.S., Crosa, J.H. and Vogel, H.J. (2009).  “Molecular characterization of TonB2 from the fish pathogen Vibrio anguilarum”.  Biochem J. 418: 49-59.

Haney, E.F., Hunter, H.N., Matsuzaki, K. and Vogel, H. J. (2009) “Solution NMR studies of amphibian antimicrobial peptides: linking structure to function?” Biochem. Biophys. Acta - Biomembranes 1788: 1639-1655

Pushie, M.J., Rauk, A., Jirik, F. and Vogel, H.J. (2009) “Can copper binding to the prion protein generate a misfolded form of the protein?” Biometals 22: 159-175.

Yamniuk, A.P., Anderson, K.L., Fraser, M.E. and Vogel, H.J. (2009) “Auxiliary calcium-binding sites can influence the structure of CIB1” Protein Sci. 18: 1128-1134.

2008

Krewulak, K.D. and Vogel, H.J. (2008). “Structural biology of bacterial iron uptake”. Biochem. Biophys. Acta1778: 1781-1804

Yamniuk, A.P., Gifford, J.L., Linse, S. and Vogel, H.J. (2008).  “The effects of metal binding loop mutations on ligand-binding to the calcium- and integrin-binding protein 1:  Evolution of the EF-hand?  Biochemistry 47:1696-1707.

Andrushchenko, V.V., Aarabi, M.H., Nguyen, L.T., Prenner, E.J. and Vogel, H.J. (2008).  “Thermodynamics of the interactions of tryptophan-rich cathelicidin antimicrobial peptides with model and natural membranes”.  Biochem. Biophys. Acta-Biomembranes 1778:1004-1014.

Chan, D.I., Hunter, H.N., Tack, B.F. and Vogel, H.J. (2008).  “Human macrophage inflammatory protein 3-alpha:  solution structure, dimerization and anti-infective properties”.  Antimicrob. Agents Chemother. 52:883-894.

Ishida, H., Huang, H., Yamniuk, A.P., Takaya, Y. and Vogel, H.J. (2008).  “The solution structures of two soybean calmodulin isoforms and their relationship to selective target-activation properties.  J. Biol. Chem. 283:14619-14628.

Ishida, H., Borman, M.A., Ostrander, J., Vogel, H.J. and MacDonald, J.A. (2008).  “Solution structure of the calponin homology (CH)-domain from smoothelin-like 1 protein:  a unique apo-calmodulin binding mode and the possible role of the C-terminal CH domain in smooth muscle relaxation”.  J. Biol. Chem. 283:20569-20578.

Pushie, M.J. and Vogel, H.J. (2008).  “Modeling by assembly and molecular dynamics of the low Cu2+ occupancy form of the mammalian prion protein octarepeat region:  gaining insight into Cu2+-mediated beta-cleavage”.  Biophys. J. 95:5084-5091.

Chan, D.I., Stockner, J., Tieleman, D.P., and Vogel, H.J. (2008).  “Molecular dynamics simulations of apo-, holo- and acyl- forms of Escherichia coli acyl carrier protein”.  J. Biol. Chem.  283:33620-33629.

2007

Chu, B., Peacock, R.S. and Vogel, H.J. (2007).  “Bioinformatic analysis of the TonB protein family”.  Biometals 20:467-483.

Rainaldi, M., Yamniuk, A.P., Murase, T. and Vogel, H.J. (2007).  “Calcium-dependent and –independent binding of soybean calmodulin isoforms to the calmodulin binding domain of tobacco MAPK-phosphatase 1”.  J. Biol. Chem. 282:6031-6042.

Gifford, J.L., Walsh, M.P. and Vogel, H.J. (2007).  “Structures and metal binding properties of the calcium-binding helix-loop-helix EF-hand motif”.  Biochem. J. 405:199-221.

Yamniuk, A.P., Silver, D., Anderson, K., Martin, S. and Vogel, H.J. (2007). “Domain stability and metal-induced folding of calcium- and integrin-binding protein”.  Biochemistry 46:7088-7098.

Andrushchenko, V., Vogel, H.J. and Prenner, E.J. (2007).  “Interactions of tryptophan-rich cathelicidin antimicrobial peptides with model membranes studied by differential scanning calorimetry”.  Biochem. Biophys. Acta-Biomembranes 1768:2447-2458.

Haney, E.F., Lau, F. and Vogel, H.J. (2007).  “Solution structures and membrane interactions of bovine lactoferrampin bound to SDS and DPC micelles”.  Biochim. Biophys. Acta-Biomembranes 1768:2355-2364.

Pushie, M.J., Ross, A.R.S. and Vogel, H.J. (2007).  “Mass spectrometric determination of the coordination geometry of diamagnetic copper (II) surrogates for the mammalian prion protein octa-repeat region.  Anal. Chem. 79:5654-5667.

Pushie, M.J. and Vogel, H.J. (2007).  “Molecular dynamics simulations of two tandem octa-repeat sites from the mammalian prion protein in its metal free and fully copper-bound states”.  Biophys. J. 93:3762-3774.

Garcia-Herrero, A., Peacock, S., Howard, S.P. and Vogel, H.J.  (2007). “Solution structure of the periplasmic domain of the TonB complex protein ExbD reveals an unexpected structural homology with siderophore-binding proteins”.  Mol. Microbiol. 66:872-889.

Metabolomics publications (Program developed with Dr. Aalim Weljie)

Bathe, O., Shaykhutdinov, R.A., Kopciuck, K., Weljie, A.M., McKay, R., Sutherland, F., Dixon, E., Sotiropoulus, O., and Vogel, H.J. (2011)  “Feasibility of Identifying pancreatic cancer based on serum metabolomics”  Cancer Epidemiol. Biomarkers. Prev. 20: 140-147.

Duggan, G.E., Hittel, D.S., Vogel, H.J., and Shearer, J. (2011).  “Differentiating short- and long-term effects of diet in the obese mouse using 1H NMR metabolomics”  Diabetes Obes. Metab. 13: 859-862.

Duggan, G.E., Miller, J., Jirik, F.R., and Vogel, H.J. (2011)  “Metabolic profiling of vitamin C deficiency in Gulo-/-mice using NMR spectroscopy”  J. Biomol. NMR 49: 165-173.

Duggan, G.E., Hittel, D.S., Tunnicliffe, J.M., Sensen, C.W., Weljie, A.M, Vogel, H.J. and Shearer, J.  (2011)  “Metabolic responsiveness to short term exercise training in lean and diet-induced insulin resistant mice” J. Appl. Physiol. 110: 1311-1318.

Booth S.C., Workentine M.L., Wen J., Shaykhutdinov R., Vogel, H.J., Ceri H., Turner R.J., Weljie A.M. (2011)  “Differences in metabolism between the biofilm and planktonic response to metal stress”  J. Proteome Res. 10: 3190-3199.

Pushie, M.J., Shaykhutdinov, R., Nazyrova, A., Graham, A. and Vogel, H.J. (2011)  “An NMR metabolomics study of elk inoculated with chronic wasting disease”  J. Toxicol. Environm. Health A. 74: 1476-1492.

Schicho R., Nazyrova A., Shaykhutdinov R., Duggan G., Vogel H.J. and Storr M. (2010) “Quantitative metabolomic profiling of serum and urine in DSS-induced ulcerative colitis of mice by 1H NMR spectroscopy.” J. Proteome Res. 9: 6268-6273

Workentine M.L., Harrison J.J., Weljie A.M., Tran V.A., Stenroos P.U., Tremaroli V., Vogel, H.J., Ceri H. and Turner R.J. (2010) “Phenotypic and metabolic profiling of colony morphology variants evolved from Pseudomonas fluorescens biofilms.” Environ. Microbiol. 12: 1565-77.

White, A.P., Weljie, A.M., Apel D., Zhang P., Shaykhutdinov R., Vogel, H.J., and Surette M.G. (2010) “A global metabolic shift is linked to salmonella multicellular development.” PLoS One 5(7): e11814.

Wishart, D.S., Knox, C., 25 coauthors, Nazyrova, A, Shaykhutdinov, R, Li, L. , Vogel, H.J. and Forsythe, I. (2009) “HMDB: a knowledgebase for the human metabolome” Nucleic Acids Res. 37: D603-D610.

Tremaroli V, Workentine ML, Weljie AM, Vogel HJ, Ceri H, Viti, C, Tatti E, Zhang P, Hynes A, Turner RJ, Zannoni D. (2009) “Metabolomics investigation of bacterial response to metal challenge.” Appl. Environm. Microbiol. 75: 719-728.

Dowlatabadi, R., Weljie, A.M., Thorpe, T.A., Yeung, E.C. and Vogel, H.J.  (2009).  “Metabolic footprinting study of white spruce embryogenesis using NMR spectroscopy”.  Plant Physiol. Biochem. 47: 343-350.

Shaykhutdinov, R.A., MacInnis, G.D., Weljie, A.M. and Vogel, H.J.  (2009). “Quantitative analysis of metabolite concentrations in human urine samples using 13C{1H} NMR spectroscopy”.  Metabolomics 5: 307-317.

Shearer, J., Duggan, G., Weljie, A.M., Hittel, D.M., Wasserman, D. and Vogel, H.J. (2008). “Metabolomic profiling of dietary-induced insulin resistance in the high fat fed C57BL/6J mouse”.  Diabetes, Obes. Metab. 10: 950-958.

Zulak, K.G., Weljie, A.M., Vogel, H.J. and Facchini, P.J. (2008).  “Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium-poppy cell cultures”.  BMC Plant Biol. 8: 5.

Hagel, J.M., Weljie, A.M., Vogel, H.J. and Facchini, P.J. (2008).  “1H NMR metabolite profiling as a functional genomics platform to investigate alkaloid biosynthesis in opium poppy”.  Plant Physiol. 147: 1805-1821.

Weljie, A.M., Newton, J., Jirik, F.R. and Vogel, H.J. (2008).  “Incorporating signals of unknown compounds in quantitative mixture analysis.”  Anal. Chem. 80: 8956-8965.

Wishart, D.S., etc., Li, L., Marrie, T., Sykes, B.D., Vogel, H.J., Querengesser, L. (2007).  "HMDB:  The human metabolome database".  Nucl. Ac. Res. 35: D521-D526.

Weljie, A.M., Dowlatabadi, R., Miller, J.L., Vogel, H.J. and Jirik, F.R. (2007).  “An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy”.  J. Proteome Res. 6: 3456-3464.