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Dr. Harvey A. Goldberg, PhD
Principal Investigator
Assistant Director, Schulich Dentistry
Professor, Dentistry Oral Biology
Professor, Biochemistry
BSc McGill, M.Phil London, PhD Alberta
- Office:
- Phone: 519.661.2182
- Email: hagoldbe@uwo.ca
Dr. Goldberg discovered his passion for bones and the biomineralization process in the 70s when he decided to do his fourth-year undergraduate project on osteogenesis imperfecta, a brittle bone disease. He hasn’t looked back since. This interest has helped Goldberg publish numerous influential papers and receive significant funding for his research.
A recent accomplishment was a Canadian Institutes of Health Research operating grant in 2013. Valued at $750,000, it is funding a project entitled “Functional Characterization of Bone Sialoprotein”. Although Goldberg is the principal investigator on this project, Schulich Medicine & Dentistry’s Graeme Hunter, PhD, and Frank Beier, PhD, have brought and will continue to bring their expertise to the project as well. “We’re interested in biomineralization - how the process of mineral formation in bones and teeth occur,” Goldberg explained.
Twenty years ago, Goldberg and Hunter published a significant paper in Proceedings of the National Academy of Science that showed bone sialoprotein was able to cause the nucleation, or the initial formation, of hydroxyapatite, the mineral found in bones and teeth. “Throughout the years, we have demonstrated this protein to have multiple functions including the ability to bind collagen and mineral, promote bone cell attachment and differentiation and drive mineral formation,” he added.
A few years ago, Goldberg and his team started working on a transgenic mouse line that was missing bone sialoprotein. In a collaborative study with Dr. Martha Somerman from the National Institutes of Health, they looked at the periodontal tissues and discovered major defects of these tissues including a disorganized and detached periodontal ligament, as well as loss of alveolar bone. It became apparent from the studies that bone sialoprotein was critical for the formation of acellular cementum, a lining of the root of the tooth, which is where the collagen of the periodontal ligament inserts into the tooth. If the acellular cementum is deficient or absent like Goldberg and his team saw in the mice, this would lead to defects similar to that seen in periodontal disease but without the inflammation. If the periodontal ligament does not attach to the tooth, ultimately the teeth become loose and the alveolar bone that surrounds the tooth is lost because of disuse.
Goldberg and his team want to figure out the mechanism to account for bone sialoprotein’s roles in bone and tooth formation. His goal is to understand what it does and how it does it, as this information could be used to develop potential therapeutics for periodontal disease and for promoting bone regeneration and repair. In spite of significant research and recent advances, Goldberg said many procedures performed and materials used in dentistry are not always based on solid scientific evidence. This is why he believes research in the field of dentistry is important. “Basic and applied research in dentistry is critical - we don’t want to see oral health professionals performing procedures with products just because companies tell them it’s the way to do things,” he said. “Evidence-based dentistry should be the rule and not the exception.”
Goldberg enjoys conducting his research, and explained providing an answer or proof that addresses a hypothesis is the rewarding part of his work. “Science is 90 per cent boredom because of the numerous control experiments and repetitions of experiments that are required, but we become truly excited with a result that clearly addresses the scientific question,” he said. “That’s the absolute high.”
- What matters from admissions? Identifying success and risk among Canadian dentistry students. Plouffe, R.A., Hammond, R., Goldberg, H.A. and Chahine, S. J. Dent Educ (2018) 82, 515 -523.
- Overlapping Functions of Bone Sialoprotein and Pyrophosphate Regulators in Directing Cementogenesis. Ao, M., Chavez, M., Chu, E., Hemstreet, K., Yin, Y., Yadav, M., Milllan, J.L., Fisher, L., Goldberg, H.A. and Somerman, M. (2017) Bone 105, 134-147
The role of bone sialoprotein in the tendon-bone insertion. Marinovich R, Soenjaya Y, Wallace GQ, Zuskov A, Dunkman A, Foster BL, Ao M, Bartman K, Lam V, Rizkalla A, Beier F, Somerman MJ, Holdsworth DW, Soslowsky LJ, Lagugn-Labarthet F, Goldberg HA. Matrix Biol. 2016 May-Jul;52-54:325-38 - Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice. Soenjaya Y, Foster BL, Nociti FH Jr, Ao M, Holdsworth DW, Hunter GK, Somerman MJ, Goldberg HA. J Dent Res. 2015 Jun 30.
- Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein. Foster BL, Ao M, Willoughby C, Soenjaya Y, Holm E, Lukashova L, Tran AB, Wimer HF, Zerfas PM, Nociti FH Jr, Kantovitz KR, Quan BD, Sone ED, Goldberg HA, Somerman MJ. Bone. 2015 Sep;78:150-64.
Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization. Holm E, Aubin JE, Hunter GK, Beier F, Goldberg HA. Bone. 2015 Feb;71:145-54. - Osteopontin mediates mineralization and not osteogenic cell development in vitro. Holm E, Gleberzon JS, Liao Y, Sørensen ES, Beier F, Hunter GK, Goldberg HA. Biochem J. 2014 Dec 15;464(3):355-64.
- Goiko, M., Dierolf, J., Gleberzon, J.S. Liao, Y., Grohe, B., Goldberg, H.A., de Bruyn, J. and Hunter, G.K. (2013) Peptides of Matrix Gla Protein Inhibit Nucleation and Growth of Hydroxyapatite and Calcium Oxalate Monohydrate Crystals. PLoS One 8(11):e80344.
- Nahar, Q., Quach, D.M.L., Darvish, B., Goldberg, H.A., Grohe, B. and Mittler, S. (2013) Orientation Distribution of Highly Oriented Type I Collagen Deposited on Flat Samples with Different Geometries. Langmuir 29(22):6680-6.
- Nene, S., Hunter, G., Goldberg, H.A, Hutter, J. (2013) Reversible Inhibition of Calcium Oxalate Monohydrate Growth by an Osteopontin Phosphopeptide. Langmuir 29(21):6287-95. PubMed
- de Bruyn J.R., Goiko, M., Mozaffari, M., Bator, D., Dauphinee, R., Liao Y., Fleming, R.L., Bramble, M.S., Hunter, G.K., Goldberg, H.A. (2013) Dynamic Light Scattering Study of Inhibition of Nucleation and Growth of Hydroxyapatite Crystals by Osteopontin. PLoS One 8(2) e56764. PubMed
- Foster, B., Soenjaya, Y., Nociti, F.H., Holm, E., Tran A.B., Zerfas, P.M., Holdsworth, D., Aubin, J.E., Hunter, G.K., *Goldberg, H.A., *Somerman, M. (2013) Deficiency in Acellular Cementum Formation and Periodontal Attachment in Bsp Null Mice. J. Dent Res 92(2) 166-172. (*authors contributed equally) PubMed
- Goldberg H.A. and Hunter, G.K. (2012) ‘Functional Domains of Bone Sialoprotein’ in Phosphorylated Extracellular Matrix Proteins of Bone and Dentin V2: 256-272. (Goldberg, M. ed.) Bentham Science Publishers.
- Kazemi–Zanjani, N., Chen, H.H., Goldberg, H.A., Hunter, G.K. Grohe B., Lagugné–Labarthet, F. (2012) Label–free Mapping of Osteopontin Adsorption to Calcium Oxalate Monohydrate Crystals by Tip–Enhanced Raman Spectroscopy. J Am Chem Soc 134(41):17076-82. PubMed
- Grohe, B., Hug, S., Langdon, A., Jalkanen, J., Rogers, K.A., Goldberg, H.A., Kartunen, M. and Hunter, G.K. (2012). Mimicking the Biomolecular Control of Calcium Oxalate Monohydrate Crystal Growth. The Effect of Contiguous Glutamic Acids. Langmuir 28, 12182-90. PubMed
- Chan, B.P.H., Vincent, K., Lajoie, G.A., Goldberg, H.A., Grohe, B. and Hunter, G.K. (2012) On the Catalysis of Calcium Oxalate Dihydrate Formation by Osteopontin Peptides. Colloids and Surfaces B: Biointerfaces 96, 22-28. PubMed
- Hug, S., Grohe, B., Jalkanen, J., Chan, B., Vincent, K., Galaretta, B., Lagugne-Labarthet, F., Goldberg, H.A. Karttunen, M., and Hunter, G.K. (2012) Mechanism of Inhibition of Calcium Oxalate Crystal Growth by an Osteopontin Phosphopeptide. Soft Matter 8, 1226-1233.
O’Young, J., Liao, Y., Xiao, C., Jalkanen, J., Lajoie, G. Karttunen, M., Goldberg, H.A. and Hunter, G.K. (2011). Matrix Gla Protein Inhibits Ectopic Calcification by a Direct Interaction with Hydroxyapatite Crystals. J. Amer. Chem Soc. 133, 18406-12. PubMed - Tanabe, N., Wheal, B., Kwon, J., Chen, H.H., Shugg, R.P., Sims, S.M., Goldberg, H.A., Dixon, S.J. (2011) Osteopontin Signals through Calcium-NFAT in Osteoclasts: A Novel RGD-Dependent Pathway Promoting Cell Survival. J. Biol Chem 286, 39871-81. PubMed
- Wynnyckyj, C.L., Omelon, S., Willett, T.L, Kyle, K., Goldberg, H. and Grynpas, M.D. (2011) Mechanism of Bone Collagen Degradation due to KOH Treatment. Biochim Biophys Acta 1810, 192-201. PubMed
- McDonald, E.E., Goldberg, H.A., Tabbara, N., Mendes, F.M., and Siqueira, W.L. (2011) Histatin 1 Resists Proteolytic Degradation when Adsorbed to Hydroxyapatite. J. Dent Res 90, 268-273. PubMed
- Forsprecher, J., Zhemeng, Z., Goldberg, H.A., Kaartinen M.T. (2011) Transglutaminase-mediated Oligomerization Promotes Osteoblast Adhesive Properties of Osteopontin and Bone Sialoprotein. Cell Adhesion & Migration 5, 65-72. PubMed
- Tenboll, A., Darvish, B., Hou, W. Duwez, A.-S., Dixon, S.J. Goldberg, H.A. Grohe, B. and Mittler, S. (2010) Controlled Deposition of Highly Oriented Type I Collagen Mimicking In Vivo Collagen Structures. Langmuir 26 (14) 12165-72. PubMed
- Hunter, G.K., O’Young, J., Grohe, B., Karttunen, M. and Goldberg, H.A. (2010) The Flexible Polyelectrolyte Hypothesis of Protein-biomineral Interaction. Langmuir 26, 18639-46. PubMed
- Wine, E, Shen-Tu, G., Gareau, M.G., Goldberg, H.A., Licht, C., Ngan, B-Y, Sorenson, E.S., Greenway, J., Sodek J., Zohar, R. and Sherman, P.M. (2010) Osteopontin Mediates Citrobacter rodentium-Induced Colonic Epithelial Cell Hyperplasia and Attaching-Effacing Lesions. Am J Path 177, 1320-32. PubMed
- Azzopardi, P.V., O’Young, J., Lajoie, G., Karttunen, M., Goldberg, H.A. and Hunter, G.K. (2010) Roles of Electrostatics and Conformation in Protein-Crystal Interactions. PLoS One 5(2):e9330. PubMed
- Baht, G.S., O’Young, J., Borovino, A., Chen HH., Tye, C.E., Karttunen, M., Hunter, G.K. and Goldberg, H.A. (2010) Phosphorylation of Ser136 is Critical for Potent Bone Sialoprotein-Mediated Nucleation of Hydroxyapatite. Biochem J. 428:385-95. PubMed
- Chan, W.D., Goldberg, H.A., Hunter, G.K., Dixon, S.J. and Rizkalla, A.S. (2010) Modification of Polymer Networks with Bone Sialoprotein Promotes Cell Attachment and Spreading. J. Biomed. Materials Res. A 94, 945-52. PubMed