What are your scientific interests?
My lab explores how epithelial stem cells maintain tissue homeostasis, regenerate after tissue damage, and form carcinomas. We use genetic manipulation of Drosophila, mouse, and human epithelial organoids to investigate mechanisms of epithelial cell polarity and proliferation control.
Ultimately, we wish to understand how the size and shape of different tissues is encoded in the genome, and how genetic mutations lead to cancer. We also have a strong interest in drug discovery, via high-throughput screening of small molecule libraries, with the aim of identifying novel agents for regenerative medicine and cancer therapy.
Name one tool you can’t do without.
CRISPR knockins and knockouts. We use this approach in all our model systems: fly, mouse and human cells.
What are your goals for your group?
In the beginning, we needed to apply for NHMRC and ARC funding, set up the lab, and start recruiting people to join us. All of these are already in process. Once up and running, we want to go after big questions in stem cell and cancer biology, and translate our findings into the clinic.
Which unresolved question would you most like to answer?
Recently, we have been interested in the Crumbs (CRB) family of cell polarity determinants, which localise apically in epithelial cells to direct cell polarity and also to regulate signal transduction via the Hippo-YAP signalling pathway.
How Crumbs proteins localise to one pole of the cell is still unsolved. During progression to carcinoma, Crumbs is lost from the apical domain just as tumour cells begin to lose their epithelial morphology and become malignant, but we still don’t know why these events happen and whether they might cause activation of YAP to drive tumour cell proliferation, invasion, and resistance to chemotherapy. The implication is that YAP may be an important drug target in almost all advanced human carcinomas.
What’s the best advice you’ve ever received?
As a PhD student at the MRC-LMB in Cambridge, Peter Lawrence (a famous Drosophila researcher) would ask us, “What’s your big question? What is it that you really want to know?” It’s a great question to ask young scientists, because we are trained to solve problems defined by others, whereas becoming an independent scientist means learning to define your own scientific problem – which then guides everything else you do.