Risk Factors For The Development Of NAFLD Beyond Insulin Resistence: Genetic, Developmental And Environmental Influences
Funder
National Health and Medical Research Council
Funding Amount
$662,052.00
Summary
Nonalcoholic fatty liver disease (NAFLD) is the presence of fat within the liver and is associated with obesity and diabetes. NAFLD occurs in approximately one in seven Australian adolescents and may lead to cirrhosis and endstage liver disease. This proposal aims to determine what genetic and developmental risk factors lead to NAFLD, in addition to examining the role of diet and exercise. This information will lead to better treatments for this condition.
The CpG Island Methylator Phenotype In Colorectal Cancer - Pathways And Precursors
Funder
National Health and Medical Research Council
Funding Amount
$517,272.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four differen ....Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four different subgroups of bowel tumours, and that each of these may have different physical properties and responses to therapy. We aim to better characterise these subgroups to increase our understanding of how normal bowel can change into a small polyp, that may grow into a cancer. Understanding the gene changes leading to each subtype of bowel cancer will in the future allow the development gene markers for early detection as well as the possibility of individualised patient therapy. We are also studying tiny biopsies of normal bowel tissue from patients either with or without polyps, to try to understand the very earliest changes which may underly the development of a bowel polyp.Read moreRead less
The Role Of Cyp2e1, Alcohol And HCV In Modulation Of Hepatocyte Homeostasis HCV Replication And Resistance To Interferon
Funder
National Health and Medical Research Council
Funding Amount
$455,520.00
Summary
Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerfu ....Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerful mediator of liver injury called tumour necrosis factor alpha. Furthermore we have shown that alcohol metabolism by Cyp2e1 results in an increase in HCV replication and negatively impacts on the anti-viral action of interferon. The studies contained within this proposal aim to build on these exciting new insights by attempting to identify new mediators and mechanisms of liver disease as a consequence of Cyp2e1 expression, alcohol and HCV replication. We will also examine the molecular mechanisms by which alcohol potentiates HCV replication. These studies will assist in developing therapeutic strategies that will benefit alcohol- and HCV-related liver disease.Read moreRead less
Clinical And Microbiological Predictors Of Post-operative Crohn's Disease Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change internat ....The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change international practice.Read moreRead less
Clinical And Microbiological Studies Of Faecal Microbiota Transplantation In Ulcerative Colitis - A Phase II, Multicentre, Randomised Double Blind, Exploratory Proof Of Concept, Placebo Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct ....Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct the inappropriate immune system activation.Read moreRead less
The Epidemiology And Burden Of Liver Disease In Australia With An Emphasis On Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$151,143.00
Summary
Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by ....Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by advanced non alcoholic fatty liver disease.Read moreRead less
Development Of Serum Models That Can Predict Clinical Outcomes In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,694.00
Summary
The overall objective of this project is to develop blood tests that can accurately predict liver related death, liver cancer and liver decompensation respectively for patients with chronic liver disease. Blood tests will also be developed to predict cardiovascular disease in patients with non-alcoholic fatty liver disease. Furthermore, we will evaluate the use of repeated blood tests to assess if this can more accurately predict death and complications compared to a single time point.
How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.