Investigating ECM inhibition of anti-tumour immunity

Invasive malignant cells coerce stromal cells to breakdown the tissue basement membrane and express unusual matrix proteins within the forming tumour microenvironment. The tumour extracellular matrix1 (ECM) is an under-investigated area of cancer biology. However, it is becoming clearer that the ECM may provide inhibitory signals to infiltrating immune cells, supporting the immunosuppressed microenvironment common both in cancer and fibrosis.

We have identified a group of ECM molecules that we call the ‘matrix index’ that are common in many human cancers. A major finding from this work has been the strong correlation of this group of ECM molecules with immunosuppressive phenotypes and poor prognosis in solid tumour patients.

In this project you will investigate the hypothesis that matrix index (MI) molecules communicate with tumour infiltrating immune cells and suppress tumour-immunity. The project is divided into two aims. Aim 1 will look at the effect of the whole tumour ECM on immunity whereas Aim 2 will investigate specific MI proteins to determine the roles of individual MI proteins in the immune response to cancer.

The project will use a combination of 3D in vitro cancer models2, bioinformatics, and antibody production to explore mechanisms of ECM induced cancer inflammation.

References
1. For background on ECM biology please see the following open access review: Hynes R.O. & Naba A., Overview of the matrisome--an inventory of extracellular matrix constituents and functions, Cold Spring Harb Perspect Biol., 2012, 4(1), a004903.

2. For background on the 3D models please see:
https://royalsociety.org/science-events-and-lectures/2016/summer-science-exhibition/exhibits/deconstructing-cancer/

Further details on how to apply for this project can be found using the Apply Online button below.

Informal enquiries
Please contact Dr. Oliver M. Pearce ([Email Address Removed])
How to Apply
Please send your covering letter (detailing why you would like to apply) and CV to [Email Address Removed]. Please indicate the project you would like to apply for. More information on the science underpinning this programme can be found at www.qmul.ac.uk/citi/ and www.ucl.ac.uk/flarre.

Deadline for applications: 1st July 2017.

Interviews will be held in the middle of July 2017.