Molecular dissection of a mesenchymal stem cell microenvironment


The activation of resident stem cells as a therapeutic approach to enhance tissue repair relies on a detailed understanding of the stem cell populations and their environments. Using the continuously growing mouse incisor as an easily accessible model system where mesenchymal stem cell behaviour is highly polarised, we have identified distinct spatially-located sub-populations of stem cells that have specific roles during tissue homeostasis. In addition, the mechanisms that convert the self-renewing stem cells into non-self-renewing progenitors that can differentiate and their inter-communication are being uncovered.
Tissue repair following tooth dentine damage in teeth is directed by Wnt/-catenin signalling-mediated mobilisation of pulp stem cells. A novel, clinically-applicable approach of enhancing this natural repair, called ReDent, has been developed that enables teeth to repair themselves following trauma or caries removal.
Paul Sharpe is the Dickinson Professor of Craniofacial Biology at Kings College London. He graduated with a degree in biology from York University and a PhD in biochemistry from Sheffield University. Following postdocs in Sheffield, Wisconsin and Cambridge he became lecturer in molecular embryology at the University of Manchester in 1987 where he established a research group working on the molecular control of tooth development. In 1991 he was recruited to his present Chair at the Dental Institute of Guy’s Hospital (later to merge with Kings College), where he established a new basic research department, the Department of Craniofacial Development and Stem Cell Biology. The department, of which he remains head, now consists of 15 academic research groups with over 80 research staff and in 2017 was awarded Centre of Excellence status: Centre for Craniofacial and Regenerative Biology. From 2002-2008 he was Director of Research for the Dental Institute.
In 2004 he was awarded the Craniofacial Biology Research Award by the International Association for Dental Research in recognition of his contribution to the understanding of how teeth develop. In 2006 and 2018 he received the William J Gies award for best publication is Biomaterials and Bioengineering from the same organisation.
His current research focusses on understanding dental pulp stem cell function and the development of stem cell-based approaches for new therapies in clinical dentistry.