Defining the role of GATA2 in lymphatic vascular development as a means to understanding how GATA2 mutations predispose to human lymphoedema
In collaboration with Professor Hamish Scott’s team at the Centre for Cancer Biology, we recently discovered that inherited mutations in the GATA2 gene predispose carriers to lymphoedema and myelodysplasia syndrome (MDS)-acute myeloid leukaemia (AML) (Kazenwadel et al., Blood, 2012). The fact that patients with GATA2 mutations develop lymphoedema highlighted an important role for GATA2 in lymphatic vessels. Our current work aims to define precisely how GATA2 controls the growth and development of lymphatic vessels, in order to understand how GATA2 mutations result in lymphoedema. Ultimately, we aim to identify new therapeutic targets to which effective therapeutics for the treatment of lymphoedema could be designed.
What we aim to achieve
Lymphatic vessels are of major importance to cancer patients. Cancer cells exploit lymphatic vessels as a “highway” for metastasis and can enter pre-existing lymphatic vessels, or promote the growth of new lymphatic vessels in order to gain access to the lymphatic vascular network and spread throughout the body. Lymphatic vessel damage following lymph node resection results in secondary lymphoedema, a disabling condition for a substantial proportion of cancer patients. There are currently no effective, curative treatments for lymphoedema. By understanding the signals that control the growth and development of lymphatic vessels, we hope to design new therapeutics that either block, or promote lymphatic vessel growth. Blocking agents should prove valuable to prevent cancer metastasis, while growth promoting agents could provide novel therapeutics for the treatment of secondary lymphoedema.
What are the next steps and milestones for your research?
Cancer Council SA's funding has been vital to progress our research and enabled us to gain new insight to the role played by the GATA2 gene in lymphatic vessels. As a result of CCSA funding we have been able to progress our work to the stage where it was awarded competitive grant funding from the NHMRC.
What motivates you to pursue cancer research?
I am motivated by the opportunity for our research to provide improved treatments for cancer patients. By identifying how cancer cells exploit the lymphatic vessel "highway" to spread to other parts of the body, we will gain the opportunity to intervene in this process and prevent metastasis. By understanding how lymphatic vessel growth and development is controlled, we will be able to design agents to promote lymphatic vessel growth and repair and thereby effectively treat lymphoedema, a major problem for cancer patients following surgery.
My message to supporters:
Without the funding provided by Cancer Council SA, we would not have been able to progress our project to the point where it was competitive for a national, 3 year grant from the NHMRC. This funding was invaluable to us. The cancer research community of SA simply would not be able to achieve the progress that has been made without the generous support and hard work of Cancer Council SA.