Zebrafish models of vascular disease: lymphatic malformation

Research Opportunity
PhD students, Honours students
Number of Honour Places Available
2
Primary Supervisor Email Number Webpage
Prof Ben Hogan Ben.Hogan@petermac.org
Co-supervisor Email Number Webpage
Dr Kazuhide Okuda

Summary 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 CRISPRinduced 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, liveimaging of development (confocal) and molecular biology approaches.

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 CRISPRinduced
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, liveimaging
of development (confocal) and molecular biology
approaches.



Research Opportunities

PhD students, Honours students
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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