Growth Factor Directed Developmental And Pathological Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$1,048,507.00
Summary
The formation of new lymphatic vessels occurs in normal development and in diseased tissues in cancer and cardiovascular disease. We have developed an understanding of how lymphatics form in development but we understand far less about how they form in disease. This project will apply multidisciplinary approaches, including genetics and computational biology, to compare how lymphatics form in development and disease. We hope to uncover new ways to manipulate this process for therapeutic gain.
Novel Transcription Factor Regulation Of Lymphatic Vascular Angiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,568.00
Summary
Lymphatic vessels control tissue fluid drainage, inflammatory processes and cancer progression. We have used genetic approaches to discover an unexpected role for a family of factors (transcription factors) that regulate new lymphatic vessel formation. This project will investigate this biological function of these genes in detail in vascular formation. The project aims to generate important knowledge for vascular biology, vascular pathologies, cancer spread and future therapeutics.
The Genetic And Cellular Control Of Lymphangiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$475,534.00
Summary
Lymphatic vessels and veins play major roles in cardiovascular disorders. In many vascular pathologies we need an ability to promote or restrict vessel formation. This research investigates the genes that control the development of new veins and lymphatic vessels. Outcomes will include a greater understanding of how our vasculature is formed, providing new knowledge that should contribute to future lymphatic and vascular therapeutic approaches.
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Understanding How GATA2 Controls Lymphatic Vessel Valve Development
Funder
National Health and Medical Research Council
Funding Amount
$697,942.00
Summary
Mutations in the GATA2 gene cause human lymphoedema as a result of the crucial role that GATA2 plays in controlling the expression of genes important for building functional lymphatic vessels. Here we aim to gain a complete picture of the cellular and molecular events that are controlled by GATA2 in lymphatic vessels and in particular, in lymphatic vessel valves.
Defining The Role Of GATA2 In Lymphatic Vascular Development As A Means To Understanding How GATA2 Mutations Predispose To Human Lymphedema.
Funder
National Health and Medical Research Council
Funding Amount
$718,890.00
Summary
We have discovered that mutations in the transcription factor GATA2 result in human primary lymphedema, a debilitating disorder resulting from the failure of lymphatic vessels to return tissue fluid to the bloodstream. The goal of this application is to define the role of GATA2 in lymphatic vessels, in order to understand how GATA2 mutations cause lymphedema. Ultimately, we aim to identify targets to which desperately needed therapeutics for the treatment of lymphedema could be generated.
The Role Of Tissue Factor Pathway Inhibitor (TFPI) In The Pathogenesis Of Lymphatic Malformations
Funder
National Health and Medical Research Council
Funding Amount
$87,198.00
Summary
Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condit ....Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condition.Read moreRead less
Characterisation Of A Newly Identified, Indispensible, Transcriptional Regulator Of Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$535,224.00
Summary
Lymphatic vessels form via lymphangiogenesis: growth of lymphatics from pre-existing vessels. This process is amenable to therapeutic intervention during metastasis because lymphatics support tumour spread. We discovered a gene that is essential for lymphangiogenesis to occur. We will investigate the control of lymphangiogenesis by this new factor. We aim to understand how it controls lymphatic vessel formation and identify genes within this pathway that have novel therapeutic potential.