Thyroid hormones are regulators of development and metabolism. The lack of concordance of thyroid function and disease in identical twins suggests that environmental effects have a significant role. Quantifying epigenetic modifications, such as DNA methylation, has the potential to identify causal effects from the environment. This research will provide a comprehensive database of DNA methylome alterations that will contribute important insights into thyroid function in health and disease.
Characterization Of Novel Regulators Of Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu ....Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.Read moreRead less
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.
Identification Of Genetic Variants Regulating Thyroid Function In Health And Disease By Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$316,433.00
Summary
Small differences in thyroid function are associated with important clinical outcomes including longevity and cardiovascular disease. We recently completed a Genome Wide Association Study and identified a novel locus associated with blood levels of Thyroid Stimulating Hormone. In this project we will extend that research to study rare genetic variants and examine their association with thyroid function in health and disease.
Understanding The Role Of RAS Mutations In Thyroid Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$463,854.00
Summary
My fellowship will examine the association of RAS mutations in thyroid cancer. RAS proteins are the most mutated in cancer and I will investigate how they work in thyroid cancer. RAS mutated thyroid cancer is more likely to cause death. This grant will be based in the pioneering lab of Prof Fagin at Memorial Sloan Kettering Cancer Center and the Garvan Institute of Medical Research. It is hoped by understanding these mutations, new treatments for thyroid cancer can be developed.