The research in my lab is focused on understanding how cells communicate with their environment and with each other using extracellular signals that induce new programmes of gene expression and regulate cell behaviour.
This phenomenon underpins embryonic development and tissue homeostasis in adult organisms, and its misregulation can cause human diseases, the most widespread being cancer.
The work in my laboratory focuses on ligands of the Transforming Growth Factor β (TGF-β) superfamily, a group of growth and differentiation factors comprising the TGF-βs, Activins, Nodals, BMPs and GDFs. These ligands play critical roles during early vertebrate development in the specification and subsequent patterning of the germ layers, and deregulation of TGF-β and BMP signalling occurs in cancer, and is important for both primary tumour formation and for metastasis.
Our goal is to understand the mechanism whereby these ligands signal from the plasma membrane to the nucleus and how they regulate transcription of target genes via activated complexes of Smad proteins. We want to determine how they function and are regulated during embryonic development, and how their activity is perturbed human disease, in particular, cancer.
To do this we use the powerful combination of an early vertebrate developmental system (zebrafish embryos) with tissue culture systems and mouse tumour models. We use methodologies ranging from molecular, cell and developmental biology to computational modelling. We anticipate that our work will lead to diagnostic and prognostic markers for cancer and eventually to new cancer therapies.
Figure 1: TGF-β superfamily ligands. A general scheme for TGF-superfamily signalling pathways, which are studied in the Hill lab in both early vertebrate development systems (zebrafish) and in tissue culture systems and mouse models. (Click to view larger image)