Engineering an in vitro model of leukaemic lymph node niche to improve drug screening for adult leukaemia.
Supervisors:
Professor Alison M Michie, School of Cancer Sciences
Professor MJ Salmeron-Sanchez, Centre for Cellular Microenvironment/James Watt School of Engineering
Doctor Hannah Donnelly, School of Molecular Biosciences / Centre for the Cellular Microenvironment
PhD Project Summary:
Chronic lymphocytic leukaemia (CLL) is the most common adult blood cancer in the Western world. CLL is characterised by an accumulation of mature clonal CD5+ B cells in blood, bone marrow and secondary lymphoid organs including lymph nodes (LN), with the survival/proliferation of CLL cells absolutely dependent on interaction with the non-malignant cells within the tumour microenvironment (TME).
The TME within lymphoid organs of CLL patients promotes interaction of the leukaemic clone with the stromal niche, made up of fibroblasts and myeloid lineage cells, and activated-CD4+CD40L+ T lymphocytes. While targeted inhibitors have revolutionized CLL patient treatment, some patients are unresponsive to these novel agents, which may in part be due to TME-associated tumour resistance, highlighting the need for more robust models for drug testing. In this exciting project the student will use state of the art bioengineering approaches to create an accurate model of the LN niche that supports the growth and survival of CLL cells.
This model will then be used to investigate LN-leukaemia biology and develop a model system to screen novel drugs for the treatment of CLL patients.