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.
Blood clotting is dependent upon platelets. A decline in platelet number, or thrombocytopenia, is a life threatening condition that can result from various diseases or importantly as a side effect of chemotherapy. We are investigating the control of platelet production. A long term goal is to stimulate platelet production in patients by boosting the natural pathways or to generate platelet producing cells for transfusion from a patient's own skin cells by genetic reprogramming.
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.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Molecular Basis For Stress-induced Gene Regulation—a Model System To Understand Transcriptional Deregulation In Cancer And Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Deregulated gene transcription plays a critical role in cancer formation. It is therefore important to understand the molecular basis of gene transcription and how tumour cells hijack the process. In this Project, we will study the molecular basis of stress-inducible gene expression. This is particularly important for understanding the molecular basis of cancer as stress-inducible genes are activated by transcription factors implicated in breast, colon, lung, and prostate cancers.
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Thyroid cancer is the commonest endocrine malignancy, and typically affects younger adults. Despite low mortality rates, local recurrence is not uncommon and re-operative surgery can cause significant morbidity. We are studying genetic variants in thyroid transcription factors associated with thyroid cancer predisposition. Our work will determine the mechanism of this association, and provide new strategies for early diagnosis and prevention of thyroid cancer.
TAF8 is a small protein that is associated with the general transcriptional apparatus. TAF8 is not an essential part of the general transcriptional machinery, but rather a regulatory molecule that appears to dictate how the machinery is used to express different genes. The absence of TAF8 leads to expression of genes controlling cell death. Since the avoidence of cell death is essential to the development of cancer these results will lead to a better understanding of how cancer develops.