Joe Parr

Delineating insulin-action pathways

My background

My interest in stem cell biology originated during a placement with The University of Cambridge where I assisted in a project to enhance the production of thrombocytes for clinical use. My subsequent degrees at The University of York in molecular cell biology and biomedical science nurtured my passion, with projects focusing on stem cell signalling and the numerous roles of insulin. Completing these research projects assured me that undertaking a PhD project would be a rewarding and exciting experience; drawing upon what inspired me during previous study and research, I took the opportunity to further delve into insulin signalling and to investigate the more unconventional pathways associated with this peptide hormone. With emphasis on the proliferative effects of insulin on cancer and the potential to exploit the signalling pathways associated with insulin for the advancement of regenerative medicine, this project combines everything that originally drew me to this field. 


My Project

While best known for its effects on cellular metabolism, the peptide hormone insulin can generate a range of cell responses including proliferation and stem cell differentiation. In addition to diabetes, this implicates insulin in a multitude of human disease states such as the development of cancer, often seen to develop in individuals undergoing treatment for type 2 diabetes mellitus. How insulin is able to bring about different context-specific cellular effects is not well-understood but is critical to advance our understanding of the treatment of diabetes and insulin-associated cancers. 

This project aims to delineate the signalling pathways emanating from insulin receptor stimulation, looking to independently analyse the downstream effects of six insulin-binding receptors, arising from alternative splicing and receptor heterodimerisation, to identify whether the different cellular responses to insulin can be linked back to individual insulin receptors. This will be performed using immortalised human mesenchymal stem cells with particular focus on cell proliferation, osteogenesis, and chondrogenesis, to generate results with physiological relevance to human cancers and musculoskeletal disorders. The ability to selectively stimulate or inhibit these receptors to generate context-specific responses in vitro will be investigated using insulin analogues displaying preferential binding to each of insulin’s receptors. 

The findings of this project may hold promise for the independent management of diabetes and cancer, and enhancement of regenerative therapies dependent on mesenchymal stem cells for the treatment of musculoskeletal conditions such as osteoarthritis.