Profile and Department: Professor, Laboratory Medicine and Pathobiology, University of Toronto
Lab: Opas’ Lab
Cell commitment and differentiation are governed by many factors, some of them extrinsic (e.g., matrix mechanics), others intrinsic (e.g., tissue-specific transcription factors and signalling pathways), many of which depend on Ca-binding proteins. One such protein is calreticulin, the cell biology of which has been the subject of research in the Opas laboratory for some time. Calreticulin is a ubiquitous calcium-binding chaperone of the ER/SR, which affects Ca homeostasis and gene expression, particularly that of steroid-sensitive and adhesion-related genes.
Our interest is in the role of calreticulin in determining the output of ES cell differentiation. Calreticulin, either by its role in Ca homeostasis or as a chaperone, modulates actions of tissue-specific transcription factors and signalling pathways that control cell lineage specification. The biomechanical properties of the cell growth niche, by modulating cell adhesiveness, shape, and cytoarchitecture, influence the resultant phenotype of ES cells. Cell adhesion and shape are also modulated by calreticulin. Thus, both cell shape and signalling pathways are affected by calreticulin expression level. Consequently, we postulate that the cell fate choice may be controlled by the combinatorial action of calreticulin level of expression and biomechanics of the substratum. Thus our research might be referred to as cytomechanics of differentiation.