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.
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.
Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
Understanding Causes Of The Rising Incidence Of Thyroid Cancer – What Can Mutations In The BRAF Oncogene Tell Us About Causes And Diagnostic Pathways For Thyroid Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$610,222.00
Summary
The occurrence of thyroid cancer has increased rapidly over the last 25 years but the cause is unknown. The increase may reflect ‘over-diagnosis’ of less harmful cancers or greater exposure to causes of this cancer. Evidence suggests that a gene mutation (BRAF) in thyroid cancers is important in understanding the drivers of the increase. This study will examine the increase in thyroid cancer by investigating causes and diagnostic pathways considering the presence or absence of BRAF mutations.
Nuclear Receptors And Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$681,979.00
Summary
This project will explore the potential for a nuclear receptor known as the thyroid receptor to suppress growth of breast cancer using cell culture models and mouse models. We hope to show that activating the thyroid receptors leads to a reduction in breast cancer growth providing evidence that the thyroid receptor pathway could be targeted for therapy.
Infant Thyroid Hormone Levels And Long-term Child Educational Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$490,495.00
Summary
Adequate levels of newborn thyroid hormones are essential for brain development.Newborn screening for thyroid hormone deficiency ensures early identification, treatment & prevention of severe intellectual disability.But there is clinical uncertainty in mildly abnormal levels.We will assess thyroid hormone levels & subsequent educational outcomes in 1.5M Australian babies.There is potential to identify infants who, without treatment, may suffer longterm disability & lower educational achievement
Schizophrenia is a serious and debilitating psychotic illness often characterized by delusions: fixed, false beliefs that preoccupy the patient and affect behaviour, and which are resistant to current drug treatments. This project investigates dysfunctions in belief mechanisms that allow delusions to form and be maintained. This will help clinicians design more effective programs of cognitive behavioural therapy for psychosis by allowing more focussed interventions to reduce delusions.
Investigating The Mechanisms That Increase Nerve-evoked Vasoconstriction Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$372,547.00
Summary
People with spinal cord injury not only lose control of their arms and legs but also lose control of their bladder and bowel. They also have poor control of blood pressure and an overfull bladder or bowel can lead to dangerously high blood pressure. In this project, we are investigating how this abnormal high blood pressure is generated. The aim is to develop treatments which target the mechanisms which increase the blood pressure responses elicited by the bladder and bowel.
Preclinical Relaxin Therapy To Reverse Cardiac Fibrosis And Gain Functional Benefits
Funder
National Health and Medical Research Council
Funding Amount
$724,754.00
Summary
Cardiac fibrosis is a key factor promoting heart disease and onset of complications including arrhythmias and heart failure. There is urgent and unmet need of drugs that can reverse fibrosis. By documenting anti-fibrotic action of a peptide hormone relaxin, CIA and his team will test therapeutic effect of relaxin in heart disease models focusing on fibrosis-reversal and functional gain, particularly arrhythmias. This work would promote development of relaxin as a new cardiovascular drug.