Dissecting the role of a novel factor in osteosarcoma progression

Osteosarcoma (OS) is the most common bone malignancy that predominately affects children and adolescents, with a secondary peak of incidence in older adulthood. Patients with non-metastatic disease have a 5-year survival rate of close to 70%; however, those with metastatic disease have a 5-year survival rate as low as 19%. Metastasis is a big clinical problem as 15-20% of OS patients present with metastases at diagnosis and 40% will eventually develop metastases. The membrane protein leucine-rich repeat containing 15 (LRRC15) is a novel type I membrane protein, which displays a restricted expression pattern in normal tissue but is highly expressed in many solid tumours. It is highly expressed on the cell surface of both the tumour cells and stromal fibroblasts in mesenchymal-derived tumours, including OS, where there is a potential association between high LRRC15 expression and poor prognosis. There is a particular need for targeted or novel agents that can be used to prevent and/or treat metastatic disease.    

Aims / Approach:

This project aims to investigate the role of LRRC15 in OS. Firstly, we will determine whether LRRC15 is required for migration and invasion of OS cells by manipulating LRRC15 levels and performing migration and invasion assays, that will include standard endpoint transwell assays, as well as more advanced microfluidic-based 3D cell culture chips with chemically defined hydrogels at around 1250Pa stiffness. Such a functional assay assesses directional cell movement in real-time using fluorescently labelled cells and offers significant advantages over the traditional assay. Secondly, we will determine the signalling changes downstream of LRRC15 in OS cells using cutting-edge third generation mRNA sequencing and bioinformatics. Thirdly, we will characterize expression of LRRC15 in FFPE OS samples with linked clinical outcome.

For further details on the project, enquiries should be directed to Dr Paul Reynolds ([Email Address Removed]).

How to apply

Informal application enquiries can be made to [Email Address Removed]. Full applications should be made via the University’s online portal.

Applications should include:

A covering letter

A full curriculum vitae

Supporting document including a list of refereed publications and key conference contributions

Research proposal

School of Medicine, University of St Andrews

The successful applicant will join a thriving research laboratory and will have the opportunity to work in an exciting and collaborative research environment, equipped to the highest international standards. The School of Medicine is located at the core of a highly interactive and vibrant research campus at the forefront of cell signalling and molecular medicine research with a focus on understanding and combating disease.

The School is committed to equal opportunities and values all applicants. The School currently has Athena SWAN bronze accreditation.