Dr. Douglas Hamilton
Associate Professor (Cross Appointment with Dentistry)
Ph.D. University of Glasgow
B.Sc. University of St. Andrews
Phone: 519-661-2111 ext. 58194
1. Design of model systems to assess the factors that govern cellular interactions with bio(active) materials.
Since the experiments by Harrison (1911) and Weiss (1945), it has been long recognized that mammalian cells are senstive to the composition of their microenvironment. Surface chemistry and topography have been observed to influence many cellular processes such as adhesion, spreading, morphology, cytoskeletal organization, proliferation, migration and gene expression. As methods of material fabrication and characterization have evolved, it has become possible to identify the limits of cell sensing and how topographical and chemical cues can influence tissue intergration around implanted materials, as well as in vitro tissue development. We are developing new model systems to evaluate cell response to biomaterial surface characteristics, using state of the art microscopy and proteomic techniques.
2. In vitro and in vivo evaluation of biomaterials and cellular response.
To date, the development of biomaterials has often been driven on an empirical basis, rather than on advances made in the understanding of cell and tissue biology/pathophysiology. Our philosophy on biomaterials development is to use biological data from in vitro and in vivo models to re-design materials that will further promote desired cell behaviour, and advantageous gene and protein expression. Through characterization of the material chemistry and topography, as well as the celluar response, materials can be further adapted where applicable, through the incorporation of biologically active molecules on the surfaces. Our philosophy on this area of research is to identify protein changes using western blotting and immunohistochemistry at different time-points, and then to identify those that are changed at the gene level. Many proteins exist stored in the golgi apparatus and endoplasmic reticulum within cells and are activated rather than transcribed. Therefore, our approach allows separation of gene changes and protein activation. Furthermore, identifcation of critical changes in genes and proteins in differentiated cells will be important for the area of stem cell differentiation, where an understanding of more than general differentiation markes will be required. We envisage developing a rigorous screening system for gene and protein changes in newly implanted, as well as end stage failure, biomaterials. Furthermore, such techniques could be used to identify gene changes in pathologies prior to the onset of implant or biomaterial failure.
3. Use of transgenic mice and proteomic/genomic techniques to assess the role of proteins in biomaterial integration in bone and connective tissue
In vitro analyses of the effects of topographical cues on mammalian cell behaviours have correlated relatively well with in vivo observations. Exactly how substratum topography regulates bone and connective tissue formation at the molecular levle remains unknown. Does short-term protein activation and translation influence long-term tissue development? Our approach to address these questions involves the use of gene knockout mice and state of the art proteomics and genomic techniques. Such an approach could lead to the identification of novel diagnostic markers and therapeutic targets that can be applied to other bone and connective tissue diseases.
For publications, please visit Dr. Hamilton's Google Scholar page.