Professor Sharpe 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 King's College London), where he established a new basic research department, the Department of Craniofacial Development and Stem Cell Biology. The department, 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. 

His main research interests are the molecular control of tooth development, dental stem cell biology and tooth bioengineering. He has published over 300 research papers including articles in Nature, Science, PNAS and Cell press. He has supervised over 50 PhD students and currently receives funding from the MRC, NIHR and NIH. He is a member of the MRC Centre for Transplantation and Biomedical Research Centre and currently serves on the MRC Regenerative Medicine Research Committee grants panel. 

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. 

Paul Sharpe is now an Emeritus Professor but is still involved in various projects and consulting with the university His current research focuses on understanding dental pulp stem cell function and the development of stem cell-based approaches for new therapies in clinical dentistry.