Hippo signalling in Natural Killer Cells maturation and function
Primary Supervisor: Professor Eric O'Neill
Project Overview
The Hippo signalling pathway is an evolutionary conserved pathway that is involved in proliferation, apoptosis, and tissue homeostasis. Recent research indicates a role for the Hippo kinases, MST1/2, and their downstream effector molecules, YAP/TAZ, in immune cell regulation. Deficiency of MST1 in mice leads to developmentally immature natural killer cells, and reduces NK cytotoxicity, indicating a role for Hippo signalling in both NK development and effector functions. The Hippo regulator RASSF1 is a scaffolding protein with the highest expression in immune cells such as NK cells and CD8+ T-cells compared to epithelial cells. Crucially, tumours often display deregulated RASSF1A:RASSF1C expression due to hypermethylation of the RASSF1A promoter which enables tumorigenesis. The function of RASSF1 in immune cells however is poorly understood. Using a combination of lentiviral-mediated knockdown with cellular and molecular biology tools our aim is to characterize the role of RASSF1, and Hippo signalling in NK cell maturation, cytotoxicity, and immune cell regulation. This will not only allow better understanding of RASSF1 expression dynamics during NK cell maturation or function, but also help to identify (immune-)signals that enable RASSF1A silencing in the tumour microenvironment.
Training Opportunities
- Development and study of mouse and cell models of cancer
- Molecular and metabolic profiling of cells and tissues
- Bioinformatics and biostatistics related to the project
- Molecular and immunological profiling