Zebrafish models of vascular disease: lymphatic malformation

Research Opportunity
PhD students, Honours students, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Primary Supervisor Email Number Webpage
Prof Ben Hogan ben.hogan@petermac.org
Co-supervisor Email Number Webpage
Dr Kazuhide Okuda

Summary The Hogan group investigates the development of lymphatic vasculature and the blood brain barrier, which play important roles in the metastatic spread of cancer and vascular disease. We use zebrafish and mice as model systems to study fundamental processes in the developing embryo. Current projects are focussed on signalling and transcriptional mechanisms that control lymphangiogenesis. We are also using large-scale genetic and genomic approaches to discover new genes essential for development of the blood brain barrier. In addition, we are interested in developing imaging tools to visualise key cell signalling events in real time in vascular development and disease models.

Project Details

Lymphatic malformation (also known as lymphangioma) is a rare childhood disease caused by uncontrolled proliferation of the lymphatic endothelium. These malformations are typically present at birth, or soon after, and are largely treated with surgery when possible. The genetic causes of lymphangioma remain to be fully understood but somatic mutations in PIK3CA, impacting the AKT-mTOR pathway, have emerged as causative in many cases. Several potential molecular therapies have been proposed but their relative utilities remain to be fully assessed. The project will generate genetic, inducible, models of lymphangioma in zebrafish and attempt to generate CRISPR-induced models. These will drive vascular malformation by expression of mutant PIK3CA expression. Phenotype will be assessed with molecular markers and confocal imaging. The models generated will ultimately be used to assess the efficacy of a series of candidate therapeutic molecules.  The project will employ transgenesis, pharmacology, live-imaging of development (confocal) and molecular biology approaches



Research Opportunities

PhD students, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


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