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The Hunter Lab



  

Hunter Laboratory
Protein Regulators of Biomineralization


Ongoing Research
Members of the Hunter Lab
Publications
Research Funding
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ONGOING RESEARCH

Protein - Crystal Interactions

Deposition of crystals in the soft tissues and fluids of the body is known as ectopic calcification, and is responsible for a wide spectrum of human diseases, including dental calculus, gout, atherosclerosis and kidney stones. Ectopic calcification is normally prevented by a system of inhibitor proteins that are either constitutively expressed or induced in response to crystal deposition.  Two important inhibitor proteins are osteopontin (OPN) and matrix gla protein (MGP).  In collaboration with Dr. Harvey Goldberg (Dentistry/ Biochemistry), Dr. Mikko Karttunen (Applied Mathematics) and Dr. Jeff Hutter (Physics & Astronomy), I am studying the interactions of OPN and MGP with two of the crystal phases associated with ectopic calcification: hydroxyapatite (HA), which is found in atherosclerotic plaque; and calcium oxalate monohydrate (COM), which is the most common mineral in kidney stones. 

These studies involve two lines of investigation.  First, we use molecular dynamics simulations to model the adsorption to crystals of “virtual peptides” corresponding to sequences of interest in OPN or MGP.  Second, we synthesize peptides corresponding to these sequences and determine their adsorption to various crystal faces using confocal microscopy and their effects on crystal nucleation and growth using scanning electron microscopy, atomic force microscopy and autotitration.  Using this combination of computational, biochemical and physical techniques, we have identified the amino acids and crystal faces constituting the protein-biomineral interface.  Our studies have led to the proposal that electrostatics and protein flexibility are critical factors in the ability of crystal-binding proteins to regulate biomineralization.

In collaboration with Dr. Walter Siqueira, I am studying the role of saliva proteins in protecting tooth enamel against acid attack.            

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MEMBERS OF THE HUNTER LAB

 

Dr. Graeme Hunter, PhD
Principal Investigator
Schulich Dentistry
Schulich School of Medicine & Dentistry
The University of Western Ontario
London, Ontario, CANADA, N6A 5C1
Phone: 519.661.2185   Fax: 519.850.2459
Emai: graeme.hunter at schulich.uwo.ca

Post Doctoral Fellow

Dr. Bernd Grohe 
Research Scientist 
bgrohe@uwo.ca
Visit Dr. Grohe's website

  

Yinyin(Heidi) Liao - Technician

YinYin (Heidi) Liao
Technician
yliao4@uwo.ca

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SELECTED RECENT PUBLICATIONS

 

J.C.-C. Hu, Y. Hu, C.E. Smith, M.D. McKee, J.T. Wright, Y. Yamakoshi, P. Papagerakis, G.K. Hunter, J.Q. Feng, F. Yamakoshi and J.P. Simmer (2008): Enamel defects and ameloblast-specific expression in enamelin knockout/lacZ knockin mice.  Journal of Biological Chemistry 283, 10858-10871 (DOI 10.1074/jbc.M710565200) Pub Med

A. Langdon, G.R. Wignall, J. O’Young, K. Rogers, E.S. Sørensen, J. Denstedt, B. Grohe, H.A. Goldberg and G.K. Hunter (2009): Kinetics of calcium oxalate crystal growth in the presence of osteopontin isoforms: an analysis by scanning confocal interference microcopy. Calcified Tissue International 84, 240-248 (DOI 10.1007/s00223-008-9215-5) Pub Med

B. Grohe, A. Taller, P.L. Vincent, L.D. Tieu, K.A. Rogers, A. Heiss, E.S. Sørensen, S. Mittler, H.A. Goldberg and G.K. Hunter (2009): The crystallization of calcium oxalates is controlled by molecular hydrophilicity and specific polyanion-crystal interactions.  Langmuir 25, 11635-11646 (DOI 10.1021/la901145d) Pub Med

G.K. Hunter, B. Grohe, S. Jeffrey, J. O’Young, E.S. Sørensen and H.A. Goldberg (2009): Role of phosphate groups in inhibition of calcium oxalate crystal growth by osteopontin. Cells Tissues Organs 189, 44-50 (DOI 10.1159/000151430) Pub Med

J. O’Young, S. Chirico, N. al Tarhuni, B. Grohe, M. Karttunen, H.A. Goldberg and G.K. Hunter (2009). Phosphorylation of osteopontin peptides mediate adsorption to and incorporation into calcium oxalate crystals. Cells Tissues Organs 189, 51-55 (DOI 10.1159/000151724) Pub Med

P.V. Azzopardi, J. O’Young, G. Lajoie, M. Karttunen, H.A. Goldberg and G.K. Hunter (2010):  Roles of electrostatics and conformation in protein-crystal interactions. PLoS One 5(2), e9330 (DOI 10.1371/journal.pone.0009330) Pub Med

S. Hug, G.K. Hunter, H.A. Goldberg and M. Karttunen (2010). Ab initio simulations of peptide-mineral interactions.  Physics Procedia 4, 51–60
(DOI 10.1016 /j.phpro.2010.08.008) Pub Med

G.K. Hunter, J. O’Young, B. Grohe, M. Karttunen and H.A. Goldberg (2010): The flexible polyelectrolyte hypothesis of protein-biomineral interaction.  Langmuir 26, 18639-18646 (DOI 10.1021/la100401r) Pub Med

B. Grohe, B.P.H. Chan, E.S. Sørensen, G. Lajoie, H.A. Goldberg and G.K. Hunter (2011): Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine. Urological Research 39, 327–338 (DOI 10.1007/s00240-010-0360-8)
Pub Med

B. Grohe, J. O’Young, A. Langdon, M. Karttunen, H.A. Goldberg and G.K. Hunter (2011):  Citrate modulates calcium oxalate crystal growth by face-specific interactions.  Cells Tissues Organs 194, 176-181 (DOI 10.1159/000324338) Pub Med

S. Hug, B. Grohe, J. Jalkanen, B. Chan, B. Galarreta, K. Vincent, F. Lagugné-Labarthet,
G. Lajoie, H.A. Goldberg, M. Karttunen and G.K. Hunter (2012): Mechanism of inhibition of calcium oxalate crystal growth by an osteopontin phosphopeptide.  Soft Matter 8, 1226-1233 (DOI 10.1039/c1sm06232h)

J. O’Young, Y. Liao, Y. Xiao, J. Jalkanen, G. Lajoie, M. Karttunen, H.A. Goldberg and
G.K. Hunter (2012). Matrix gla protein inhibits ectopic calcification by a direct interaction with hydroxyapatite crystals.  Journal of the American Chemical Society 133, 18406-18412
(DOI 10.1021/ja207628k) Pub Med

B.P.H. Chan, K. Vincent, G. Lajoie, H.A. Goldberg, B. Grohe and G.K. Hunter (2012): On the catalysis of calcium oxalate dihydrate formation by osteopontin peptides.  Colloids and Surfaces B: Biointerfaces 96, 22-28 (DOI 10.1016/j.colsurfb.2012.03.015)

B. Grohe, S. Hug, A. Langdon, J. Jalkanen, K.A. Rogers, H.A. Goldberg, M. Karttunen and
G.K. Hunter (2012).  Mimicking the biomolecular control of calcium oxalate monohydrate crystal growth: The effect of contiguous glutamic acids.  Langmuir 28, 12182-12190 (dx.doi.org/10.1021/la3018985)

N. Kazemi-Zanjani, H. Chen, H.A. Goldberg, G.K. Hunter, B. Grohe, F. Lagugné-Labarthet (2012).  Label-free mapping of osteopontin adsorption to calcium oxalate monohydrate crystals by tip-enhanced Raman spectroscopy.  Journal of the American Chemical Society
134, 17076-17082

G.K. Hunter (2012): Role of osteopontin in modulation of hydroxyapatite formation.  Calcified Tissue International (in press)


History of Science

G.K. Hunter: Phoebus Levene and the Tetranucleotide Structure of Nucleic Acids. Ambix 46,
73-103 (1999)

G.K. Hunter: Vital Forces: The Discovery of the Molecular Basis of Life, Academic Press (2000)

G.K. Hunter: Light Is a Messenger: The Life and Science of William Lawrence Bragg, Oxford University Press (2004)

G.K. Hunter: Dorothy Mary Crowfoot Hodgkin. In: New Dictionary of Scientific Biography
(N. Koertge, ed.), Vol 3, pp333-339, Charles Scribner’s Sons (2008)

G.K. Hunter: Dorothy Mary Crowfoot Hodgkin. In: New Dictionary of Scientific Biography
(N. Koertge, ed.), Vol 3, pp333-339, Charles Scribner’s Sons (2008)

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RESEARCH FUNDING

 The following agencies support ongoing research in the lab.

NEWS
 

 

 

 

 

 

 

Dr. Graeme Hunter received the Distinguished Scientist Award for Basic Research in Biological Mineralization from the International Association for Dental Research.

This award is designed to stimulate, encourage, and re-cognize basic research in the field of biological mineral-ization. Evidence must be presented of original thought and accomplishment in the field of calcification. This should include work done on the mechanism of mineralization in biologic systems, including teeth, bone, ectopic deposits, or model systems.


PREVIOUS PRESENTATIONS:

38thMeeting of the American Association for Dental Research. Washington, DC, March 3-6, 2010 (keynote address)

FASEB Conference on Osteopontin and Related Proteins. Steamboat Springs, Colorado, August 1-6, 2010

10thInternational Conference on the Chemistry and Biology of Mineralized Tissues. Carefree, Arizona, November 7-12, 2010

Symposium on biomineralization, Materials Research Society fall meeting. Boston, November 29-December 3, 2010 

Department of Chemistry. UWO, February 9, 2011

18th American Conference on Crystal Growth and Epitaxy. Monterey, California, July 3-August 5, 2011 

Department of Chemistry, University of Waterloo, Nov. 23, 2011

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CONTACT INFORMATION 

Please direct research position and other inquiries to:

Dr. Graeme Hunter
Schulich Dentistry
Schulich School of Medicine & Dentistry
The University of Western Ontario
London, ON, CANADA  N6A 5C1
Phone: 519.661.2185
Fax: 519.850.2459
Email: graeme.hunter at schulich.uwo.ca  


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