Department: Medical Biophysics, University of Toronto
Research in our lab is focused on skeletal development. Osteogenic cells develop continuously throughout life from a pool of multipotent mesenchymal stem cells and primitive osteo- and chondroprogenitor cells. Our work addresses both how to characterize and how to control – by endogenously produced or exogenously supplied hormones, cytokines, and growth factors – self-renewal, proliferation and differentiation of the stem, committed progenitor and more mature precursor populations. We have acquired evidence for differentiation stage-specific regulatory pathways and for dose-, and time-dependent biphasic effects of many regulators of interest. We have also developed assays in which transitional stages from very primitive multipotent progenitor cells to the apparently terminally-differentiated post-proliferative cell can be identified based on their molecular profiles. Modeling of expression profiles has predicted an unexpected developmental flexability, i.e., that mesenchymal progenitors may express different developmental bifurcation points and transit different routes to achieve the same end point phenotype. Whether this underlies the endpoint hetereogeneity seen in mature osteoblasts in vitro and in vivo is one area of ongoing studies in the lab. We are also identifying how new mutations that affect skeletal development and bone turnover impact mesenchymal stem cell and osteoprogenitor self-renewal, differentiation and activity.