Hippo – a new signalling pathway for melanoma targeting

The Hippo molecular signalling pathway, only recently discovered by A/Prof Harvey and collaborators (Cell 114:457, Nat Cell Biol 15:1176), is a key regulatory mechanism in multiple cancers. For example, data is rapidly emerging that central mediators of Hippo signalling, such as the oncoprotein YAP, drive the growth, survival and metastasis of melanoma. These studies are spurring the development of novel treatments that inhibit YAP function and that are expected to be effective in a range of cancers.

This project will focus on studies of Hippo pathway regulation in melanoma, with a strong translational focus. It is anticipated that the student’s work will define a path to clinical testing of Hippo targeting in melanoma and others cancers. Techniques involved will include working with human tumour specimens and linked clinical data, mouse handling, in vivo drug treatment, immunostaining, flow cytometry, genomics techniques and molecular biology assays.

This project will be supervised by Dr Mark Shackleton (Cancer Development & Treatment Lab) and Associate Professor Kieran Harvey (Cell Growth & Proliferation Lab).

Research interests:
Cancer Development & Treatment Lab: Melanoma is a common cancer and a source of significant morbidity and mortality in our community, particularly among 20-40 year-olds where it is the most common cause of cancer death. As a result, melanoma causes the second/third most years of lost productive life of all cancers in males/females. Disturbingly, the incidence of melanoma is increasing in Australia and deaths attributable to the disease are projected to increase accordingly. Compounding the increasing disease and economic burden imposed by melanoma in our community is the lack of effective therapies for patients with advanced disease.

Our research program seeks to address the problem of melanoma using two approaches. First, through improving understanding of normal melanocyte development, we aim to identify mechanisms of melanomagenesis and thereby develop strategies for improved disease prevention. Second, through use of a highly efficient model of human melanoma progression that replicates closely the biology of this disease in patients, we aim to identify mechanisms of melanoma propagation and metastasis. Our close links with the clinical research activities of the Peter Mac Melanoma Unit enable rapid clinical translation of our lab discoveries in order to help patients.

Cell Growth & Proliferation Lab: Researchers study mechanisms that control organ size during development, and how deregulation of these processes contributes to human cancer.