I am a physiologist working to understand how disturbances during pregnancy can alter fetal development and increase the risk of developing adult onset diseases such as cardiovascular disease, renal disease and diabetes. In particular I am interested in how alterations in kidney development may play a crucial role in disease development.
Mechanisms Involved In Reduced Cardiac Contractility As A Consequence Of Growth Restriction During Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$317,810.00
Summary
Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal phy ....Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal physiology is imperative to subsequetly understand pathological states, such as interuterine growth restriction (IUGR). In Australia, the incidence of IUGR leading to low birth weight babies is 7%. IUGR is caused by maternal undernutrition, maternal smoking-drug use and placental insufficiency. It is associated with an increase in perinatal mortality, respiratory problems, SIDS and morbidity. Epidemiological studies show that low birth weight babies are also at an increased risk of cardiovascular disease, including heart failure, in adult life. To date, there is little information on the impact of fetal growth restriction on the normal development and function of the heart muscle. Understanding the impact of IUGR on heart muscle development will allow the elucidation of the underlying physiological mechanisms linking these two temporally distinct events. This mechanistic understanding will allow improved clinical management of those individuals at risk of cardiovascular disease in adult life arising from IUGR. It may also allow for early intervention strategies that can improve cardiovascular function. Therefore, we propose to examine both the normal developmental changes to E-C coupling so that we can understand how placental insufficiency leading to IUGR impairs normal heart muscle development. This will result in impaired function at a cellular level, which will ultimately manifest as an increased susceptibility of the heart to injury in later life.Read moreRead less
A lack of oxygen in the kidney (hypoxia) is a primary cause of kidney disease, but the mechanisms are not clear. To determine the processes involved, we will take a new approach; combining a mathematical model with studies of kidney oxygen regulation in both normal and diseased kidneys. We will determine the causes of hypoxia in kidney disease, and find out if preventing hypoxia has the potential to be a treatment for kidney disease.
The Consequences Of Simulated Shift Work Exposure During Gestation On The Metabolic Health Of The Adult Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Shiftwork is associated with increased risk for preterm birth & spontaneous abortion. In an animal model simulated shiftwork exposure during pregnancy increases fat deposits & reduces glucose tolerance in the adult offspring, suggesting exposure during pregnancy has lifelong health consequences for the progeny. This project will investigate the impact of shiftwork during gestation on the metabolic health of the offspring, & determine the stage of pregnancy most susceptible.
Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human deve ....Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human development, with consequences for biological and social function and behaviour throughout the lifecourseRead moreRead less
Mechanisms Responsible For Hypertension Caused By Perinatal Omega-3 Fatty Acid Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$280,650.00
Summary
Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) ....Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) for the first time that the essential omega-3 fatty acid, alpha-linolenic acid (ALA), supplied in the early developmental period, affects blood pressure later in life. The work showed that moderate omega-3 fatty acid deficiency in the perinatal period resulted in hypertension, despite reversal of the deficiency at a time months before the assessment of blood pressure. These findings are suggestive of a critical period, during which time the development of normal blood pressure control mechanisms appears, at least partially, dependent upon the supply of omega-3 fatty acids. These findings suggest that omega-3 deficiency early in life may affect fatty acid metabolism, transport or uptake systems, such that re-feeding of the nutrients is functionally ineffective. Alternatively, deficiency of omega-3 fatty acids early in life may arrest development of one or more of the key signalling pathways in the control of blood pressure, such as the Brain Angiotensin System. The influence of dietary omega-3 fatty acid supply, relative to the critical period, on expression of genes involved in the control of blood pressure as well as in fatty acid metabolism, will be defined. Also, the role of the brain angiotensin system in omega-3 fatty acid deficiency-induced hypertension will be determined. We expect that the results of this study will profoundly affect hypertension research, as well as nutrition, particularly that for infants.Read moreRead less
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less