Biography

Research Interests

The major cause of tooth loss in the U.S. is due to caries, and the cost in health care dollars to treat and retreat this disease amounts to 20-30 billion dollars per year. New and novel ways of treating this disease are needed, such as enhancing remineralization of carious lesions and producing biologically active restorative materials, to offer to patients in the future, alternative treatment modalities, to the conventional restorative materials, amalgam, composite etc. Of particular interest in this search for novel types of treatments is the human non-collagenous proteins, especially phosphophoryn (PP) and dentin sialophosphoprotein (DSP) as they are intimately involved in the mineral nucleation and crystal growth in dentin. We are studying the binding mechanism and how tightly these proteins bind to the surface of hydroxyapatite crystals, and how this binding ultimately affects the growth of the crystals. This is done by taking advantage of the latest developments in the area of nanotechnology. In particular, we use carbon-nanotube tips grown on commercially available Atomic Force Microscope (AFM) tips, and polyamidoamine (PAMM) dendrimers. This allows the charged state of single crystal surfaces to be mapped, and the surface interaction with human dentin non-collagenous proteins examined.

To further clarify the role played by PP in the remineralization (and mineralization) of human dentin, we are investigating how both the quantity and quality, as defined by protein sequence, molecular weight, amino acid and immunoreactivity, affect the mineral composition, crystal orientation and mineral distribution in remineralized (repaired) dentin, on the assumption that this repaired tissue will exhibit certain relevant clinical characteristics, that is: be less susceptible to demineralization; be amenable to the bonding of restorations; and be physiologically functional.

We are also investigating the relationship between PP and DSP secretion and up regulation of certain growth factors that are sequestrated in dentin, with the idea that this will help us to ultimately control reactionary dentin formation. In order to establish a model for this activity, studies include investigating the ability of odontoblasts to specifically express transduced wild type or mutant DSPP in a human tissue culture system and demonstrating human PP and DSP expression under carious lesions. This basic knowledge will be used to design new clinical treatment modalities and intervention approaches to control pulpal responses to caries and induce repair of diseased dentin.

Selected Publications

CLARKSON, B.H., CHANG, S.R., HOLLAND, R.  Phosphoprotein analysis of sequential extracts of human dentin and the determination of the subsequent remineralization potential of these dentin matrices, Caries Research , 32(5): 357-364, 1998

STROTHER, J. M., KOHN, D.H., DENNISON, J.B. and CLARKSON, B.H.  Fluoride release and reuptake in direct tooth colored restorative materials. 

Dent. Materials, 14:129-136, 1998

GU, K, CHANG, S.R., CLARKSON, B.H., RUTHERFORD, B. AND RITCHIE, H.  Human dentin phosphophoryn nucleotide and amino acid sequence.

Eur J. Oral Sci, 10G:1043-1047, 1998

Gu K, Chang SR, Ritchie HH, Clarkson BH, Rutherford RB (2000) Molecular cloning of a human dentin sialophosphoprotein gene. Eur J Oral Sci 108(1):35-42.

Tsai S, Rutherford RB, Clarkson BH, Chiego Jr. DJ, Kohn DH.  Atomic force microscopy/picoindentation to quantify local mechanical properties of human root dentin.
 Proc. Mater. Res. Soc. Symp.: Biomedical Materials (2000) 16:11-13