Tissue mechanics: A driver of pathogenesis in B-cell non-Hodgkin’s lymphomas (B-NHL) and a therapeutic opportunity?

Applications will be reviewed until a suitable candidate is appointed.

You will be working as part of a highly motivated team in the haematology section of the cancer medicine department; many of our past student have entered a career in academic haematology, or medical research. The project involves working with patient samples in order to understand disease processes in order to discover potential new treatments which will improve lives.

B-NHL are the most common leukaemias in Western countries. Whilst prognosis has improved with the advent of novel therapies the median survival of patients with bulky lymphadenopathy 3-5 years. As with solid tumours, lymphomas, modify their microenvironment in order to facilitate the growth and survival of the malignant cells; and provide protection from therapy. In vitro cultures have been used as models of the lymph node (LN) microenvironment; however, they do not reflect complexity of the tissue, and are 2D. In a similar way, mouse models do not recapitulate the heterogeneity of these diseases. Furthermore, the role of tissue mechanics, well established in the pathogenesis of solid tumours, has not been explored. This is especially surprising as signals from two of the molecules which are of pathogenic and prognostic importance, the B-cell receptor and the integrin α4β1, are modified in response to microenvironmental forces. This PhD project will form part of a strategy to model these interactions in vivo, examining the role of stromal cells together with mechanical and biochemical factor in the pathophysiology of B-NHL. We anticipate that our model will enable us to identify signals that are important in protecting B-NHL cells in LN from treatment; examine ways to overcome them, and thereby increase the life expectancy of this group of patients.

The project is suited to a student with a good MSc. or equivalent in a biological/medical science.

Applicants are encouraged to contact the Principal Supervisor, Dr Kathy Till on: [Email Address Removed] to discuss their application and the project.