Downward lab

Oncogene Biology Laboratory

: Areas of interest

Our interests include the mechanisms by which cells respond to external signals that regulate their proliferation and survival, in particular the signalling pathways along which information is transferred leading from cell surface receptors to events in the cell nucleus, and how these are altered during the process of malignant transformation.

We have characterised the molecular details of how Ras oncoproteins, which are mutationally activated in 20 per cent of human tumours, are regulated and how they transmit their signal to the cell through direct binding to multiple effector proteins including Raf and phosphatidylinositol 3-kinase.

We are using whole genome scale RNA interference libraries to identify new components of critical growth regulatory pathways. In addition, we are screening for genes that are required for the survival of Ras transformed, but not normal, cells and also for genes that when disrupted may restore the sensitivity of drug resistant tumour cells to established chemotherapeutic agents.

We are also interested in how these signaling pathways can promote the ability of tumours to hide themselves from the immune system. Removing these immune evasion mechanisms is likely to be necessary to enable complete eradication of tumours during therapy.