We have shown that premature birth leads to abnormalities in kidney structure and function. This project will determine in human infants, whether premature birth when combined with poor growth in the womb leads to an increase in these kidney abnormalities. Using animal studies we will examine specific factors which may adversely impact on kidney growth before and after premature birth. The findings are very relevant to the long-term kidney health of indigenous Australians.
Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.
Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili ....Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.Read moreRead less