Marta Emperador – Targeting the extracellular matrix (ECM) in therapy resistant paediatric tumours
|Supervisor:||Dr. Ina Oehme|
|Co-Supervisors:||Prof. Dr. Roland Kappler and Dr. Silvia Boj|
|Secondments:||LMU (Germany) and Hub for Organoids (Netherlands)|
|Enrolment in Doctoral Program:||Helmholtz International Graduate School for Cancer Research|
|PhD awarded by:||University of Heidelberg|
In this project the role of collagen, matrix metalloproteinases (MMPs) and the ECM in therapy resistance and differentiation in primary and therapy resistant relapsed (INFORM) paediatric tumours is to be examined, as well as the possibility of targeting the ECM (e.g. by application of MMP inhibitors or LOX inhibitors) in an effort to overcome therapy resistance. When targeting the ECM, both the response in viability and the cells ability to migrate and invade are to be examined. Viability will be assessed by metabolic activity, trypan blue exclusion and colony formation assays. Through high content imaging an additional layer of information will be added, enabling the discrimination between cytotoxic and cytostatic effects. Invasion and migration will be studied in cell culture bases assays (Boyden-chamber) as well as in a zebrafish larvae model by assessing dissemination of tumor cells from a localized tumor to the tail region of the fish larvae.
We expect to find a novel druggable vulnerability by up- or down-regulated ECM components, which will also allow the elucidation of the pathways involved.