Research Interests
Signalling Networks and the Tumour Microenvironment
Collagen is the most abundant protein in the human body and its role in maintaining structural integrity is well documented.
However collagen also functions as a signalling molecule and exerts profound influences on cellular behaviour. The Discoidin Domain Receptors (DDRs) are a unique class of Receptor Tyrosine Kinases (RTKs) that bind collagen rather than soluble growth factors. These receptors have been implicated in a number of diseases including osteoarthritis, hepatic fibrosis and cancer.
Our studies focus on the determination of the signalling networks downstream of the DDRs and establishing how these receptors modulate cellular decisions such as cell growth, apoptosis and differentiation. The goal of these studies is to gain new biological insights into the processes by which extrinsic signals from collagen integrate with intrinsic cellular signals to determine cell fate.
Receptor Tyrosine Kinase Coactivation Networks
Genetics and molecular pathology have revealed many of the genes commonly deregulated in cancer.
There is an increasing appreciation that cellular processes are governed by signaling components working within the context of interconnected networks. In particular, it appears that it is the deregulation of signaling networks rather than individual genes that are ultimately responsible for many of the pathogenesis of cancer.
We have previously shown that cancer cells employ receptor tyrosine kinase (RTK) coactivation as a mechanism to maintain network robustness and overcome chemotherapy. In collaboration with clinician-scientists, we build on these studies by extending our proteomic analyses to in vivo and ex vivo models of human tumours.
Our aim is to achieve a better understanding of the information processing principles downstream of multiple RTKs. By determining the mechanisms by which tumour outcomes are controlled by this complex web of RTKs, we hope to develop novel network-based therapeutic strategies for this disease.
Protein Network Team
We use systems biology and engineering approaches to understand how protein signalling networks control cancer outcomes such as chemoresistance and tumour progression.
