Deciphering mammalian MST/hMOB1/NDR/LATS tumour suppressor networks. (360G-Wellcome-090090_Z_09_Z)
The main objective of my research is to determine how deregulated MST/hMOB/LATS/NDR signalling (also termed mammalian Hippo signalling) contributes to cellular transformation. The main aim is to delineate the key molecular events in mammalian Hippo networks essential for tumour suppression. To achieve this goal I propose the following specific aims: Project 1: Define the molecular role(s) of mammalian NDR1/2 kinases in centrosome biology, the cell cycle and cellular transformation. Project 2: Determine the precise function(s) of LATS2 kinase in cell cycle progression and EMT relating to cancer development. The objective is to decipher mammalian Hippo signalling by selectively manipulating kinase activities or by disrupting specific complexes. To achieve these goals, I will employ an interdisciplinary approach that combines biochemical, molecular and cell biological methods, thereby allowing controlled overexpression, inactivation and depletion/loss of our proteins of choice (p lease see the detailed research plan for details). The precise characterisation of MST/hMOB/LATS/NDR tumour suppressor networks has also the potential to open novel avenues in the pursuit of compounds for cancer treatment. Understanding where, how and why mammalian Hippo signalling is required for tumour suppression will also establish how far NDR/LATS pathway members are suitable therapeutic biomarkers in the fight against human diseases.
£838,863 23 Jun 2009