Research into the prevention and causes of leukaemia and lymphoma in people of all ages. The design of therapeutic agents for the treatment of cancer is an extremely promising avenue of research, with many new drugs entering clinical trials and improving the outcome of cancer treatments.
Understanding the signalling pathways that promote cancer is therefore essential not just for choosing the molecules to target by new drugs, but also to determine which cancers each drug is most appropriate for. We have recently shown that the tumour suppressor proteins, Discs large and Scribble, which were previously implicated in solid tumours, also play a role in regulating the biology of blood cells.
This discovery suggests that Scribble and Discs large might also act as tumour suppressors in lymphocytes. Furthermore, using genetic analyses in the vinegar fly, Drosophila, we have shown that Scribble cooperates with another signalling protein named Notch, to regulate solid tumour progression.
Notch is well known to affect progression of human and mouse leukemias, suggesting that Scribble and Notch might cooperate to affect the onset and progression of leukemia. In this study, we will test for the first time whether Scribble can act as a tumour suppressor in lymphocytes, determine whether Scribble cooperates with Notch in leukemogenesis, and explore the molecular mechanisms by which the Scribble and Notch signalling pathways might interact.
These studies will be performed using fly and mouse models of cancer. These studies will provide opportunities for diagnostic and therapeutic management of leukemia.