Hunter Laboratory
Protein Regulators of Biomineralization

Ongoing Research
Members of the Hunter Lab
Publications
Research Funding
News
Contact Information
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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
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
Email - graeme.hunter@schulich.uwo.ca

	Dr. Graeme Hunter, PhD  Principal Investigator graeme.hunter@schulich.uwo.ca
	Dr. Bernd Grohe  Research Scientist  bgrohe@uwo.ca Visit Dr. Grohe's website
	YinYin (Heidi) Liao Technician yliao4@uwo.ca
	Jari Jalkanen Postdoctoral Fellow jjjalkanen@gmail.com
	Susanna Hug PhD Candidate shug1@uwo.ca
	Jason O'Young Summer Student oyoung@rogers.com

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PUBLICATIONS

• H. Zhang, G.K. Hunter, H.A. Goldberg, G.A. Lajoie and K.K.-C. Yeung. An integrated procedure of selective injection, sample stacking and fractionation of phosphopeptides for MALDI MS analysis.  Analytica Chimica Acta 581, 268-280 (2007)  Pub Med

• R.M. Wazen, C.E. Tye, H.A. Goldberg, G.K. Hunter, C.E. Smith and A. Nanci. In vivo functional analysis of polyglutamic acid domains in recombinant bone sialoprotein. Journal of Histochemistry and Cytochemistry 55, 35-42 (2007)  Pub Med

• J.A.R. Gordon, A.V. Sampaio, T.M. Underhill, G.K. Hunter and H.A. Goldberg. Bone sialoprotein expression affects bone nodule formation and osteoblast differentiation. Bone 41, 462-473 (2007)  Pub Med

• A. Taller, B. Grohe, K.A. Rogers, H.A. Goldberg and G.K. Hunter. Specific adsorption of osteopontin and synthetic polypeptides to calcium oxalate monohydrate crystals. Biophysical Journal 93, 1768-1777 (2007)  Pub Med

• B. Grohe, J. O’Young, A. Ionescu, G. Lajoie, K.A. Rogers, M. Karttunen, H.A. Goldberg and G.K. Hunter.  Control of calcium oxalate crystal growth by face-specific adsorption of an osteopontin phosphopeptide.  Journal of the American Chemical Society 129, 14946-14951 (2007)  Pub Med

• 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. Enamel defects and ameloblast-specific expression in enamelin knockout/lacZ knockin mice.  Journal of Biological Chemistry 283, 10858-10871 (2008)  Pub Med

• G.S. Baht, G.K. Hunter and H.A. Goldberg.  Bone sialoprotein-collagen interaction promotes hydroxyapatite nucleation.  Matrix Biology 27, 600-608 (2008)  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. 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 (2009)  Pub Med

• J.A.R. Gordon, J. Sodek, G.K. Hunter and H.A. Goldberg. Bone sialoprotein stimulates focal adhesion-related signaling pathways: role in migration and survival of breast and prostate cancer cells.  Journal of Cellular Biochemistry 107, 1118–1128 (2009)  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.  The crystallization of calcium oxalates is controlled by molecular hydrophilicity and specific polyanion-crystal interactions.  Langmuir 25, 11635-11646 (2009)  Pub Med

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

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

• J.A.R. Gordon, G.K. Hunter and H.A. Goldberg.  Activation of the mitogen-activated protein kinase pathway by bone sialoprotein regulates osteoblast differentiation.  Cells Tissues Organs 189, 138-143 (2009)  Pub Med

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

• G.S. Baht, J. O’Young, A. Borovina, H. Chen, C.E. Tye, M. Karttunen, G. Lajoie, G.K. Hunter and H.A. Goldberg.  Phosphorylation of Ser136 is critical for potent bone sialoprotein-mediated nucleation of hydroxyapatite crystals.  Biochemical Journal 428, 385-395 (2010)  Pub Med

• W.D Chan, H.A. Goldberg, G.K. Hunter, S.J Dixon and A.S Rizkalla.  Modification of polymer networks with bone sialoprotein promotes cell attachment and spreading.  Journal of Biomedical Materials Research Part A 94, 945-952 (2010)  Pub Med

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

• B. Grohe, B.P.H. Chan, E.S. Sørensen, G. Lajoie, H.A. Goldberg and G.K. Hunter. Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine.  Urological Research DOI 10.1007/s00240-010-0360-8 (published online, Jan 14, 2011  Pub Med

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

G.K. Hunter, J. O'Young, B. Grohe, M. Karttunen, H.A. Goldberg. The Flexible Polyelectrolyte Hypothesis of Protein-Biomineral Interaction. Langmuir 26(24):18639-46 (2010)  Pub Med

• J. O’Young, Y. Liao, Y. Xiao, J. Jalkanen, G. Lajoie, M. Karttunen, H.A. Goldberg and G.K. Hunter.  Matrix Gla Protein Inhibits Ectopic Calcification by a Direct Interaction with Hydroxyapatite Crystals.  Journal of the American Chemical Society (doi/abs/10.1021/ja207628k) Pub Med

• B. Grohe, B.P.H. Chan, E.S. Sørensen, G. Lajoie, H.A. Goldberg and G.K. Hunter. Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine.  Urological Research 39, 327–338 (2011) Pub Med

 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: Michael Smith. In: New Dictionary of Scientific Biography (N. Koertge, ed), Vol. 6, pp478-483, Charles Scribner’s Sons (2008)

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RESEARCH FUNDING

 The following agencies support ongoing research in the lab.

• Canadian Institutes of Health Research
• Canadian Arthritis Network

NEWS

In 2009, Dr. Hunter received the Distinguished Scientist Award for Basic Research in Biological Mineralization from the International Association for Dental Research

Recent and Upcoming presentations:

• 38^thMeeting 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


• 10^thInternational 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


• 18^th 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@schulich.uwo.ca

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