The Hippo pathway and Yap1 in vascular growth control in development and disease

Lymphatic vessels play roles in the drainage of tissue fluid, trafficking of immune cells and the metastatic spread of cancer. Inhibiting or enhancing the development of new lymphatic vessels has therapeutic potential in a host of diseases including cancer, ocular disease, cardiovascular disease and rare inherited disorders. The Hogan lab uses genetic approaches in zebrafish and mice to discover and characterise new molecular regulators of lymphangiogenesis (the formation of new lymphatics). We recently described a role for Yap1 in lymphangiogenesis in the zebrafish embryo, in response to Vegfc/Vegfr3 signalling. This work, and work from others, has confirmed that the Hippo pathway and Yap are central in vascular growth during development, yet how they control angiogenesis, lymphangiogenesis, vessel proliferation and vascular network patterning remains far from understood.

This PhD candidate will use molecular genetics, biochemical approaches and live imaging of cellular behaviours in zebrafish, mice and cultured human cell lines to understand the mechanistic control of vascular development by the Hippo pathway and Yap. The project will generate novel CRISPR mutants, new transgenic lines and utilise single cell sequencing of developing vasculature. We will also investigate metabolic control by the pathway in vascular growth and development. Finally, the project will have the opportunity to assess tumour vasculature and pathological settings to understand the role of this pathway in vascular disease scenarios.

In the Hogan lab, researchers investigate the development of lymphatic vasculature and the blood brain barrier, which play important roles in the metastatic spread of cancer. Specifically, we aim to:
- Characterise signalling and transcriptional mechanisms that control lymphangiogenesis using studies in zebrafish and mice.
- Discover new genes essential for development of the blood brain barrier using zebrafish genetics.
- Develop imaging methods to visualise signalling in real time during tissue morphogenesis.
- Model cellular pathologies of vasculature in cancer and vascular disease.
https://www.petermac.org/research/labs/ben-hogan

Peter MacCallum Cancer Centre in Melbourne Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
https://www.petermac.org/education/research-education

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program