Molecular Mechanisms of Lymphangiogenesis in Development and Disease.

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Lymphatic vessels are a vital component of the cardiovascular system and serve several functions critical to embryonic development and adult health. These include: 1. The uptake, transport and return to the bloodstream of tissue fluid and protein. 2. The uptake and transport of lipids from the digestive tract. 3. The transport of cells of the immune system that fight infection. Abnormalities in the development and function of lymphatic vessels are associated with a large number of human diseases. These include primary and secondary lymphoedema, inflammatory diseases such as psoriasis, rheumatoid arthritis and and asthma, and malignancies of the lymphatic vessels such as lymphangiosarcoma and Kaposi's sarcoma. Lymphatic vessels are also critical for the progression of many forms of cancer, by virtue of the fact that tumour cells exploit lymphatic vessels as a transport route for metastases. Diseases in which lymphatic vessels are involved therefore impact on a significant proportion of the Australian population. Our current knowledge of the mechanisms by which the lymphatic vascular network is constructed during embryonic development, and deregulated in disease states, is extremely limited. Once the molecular mechanisms of disease origin are established, much needed novel therapeutics to treat patients suffering from lymphatic vascular diseases can be designed. Treatments targeted to prevent the aberrant growth of lymphatic vessels are vital to halt tumour metastasis and the progress of inflammatory diseases, while treatments targeted to stimulate the development of new lymphatic vessels are necessary to treat diseases in which lymphatic vessels are hypoplastic, such as lymphoedema. This project aims to advance our understanding of lymphatic vascular development and function, in order to provide the opportunity to benefit patients suffering from all spectrums of lymphatic vascular disease.