Obesity is associated with type 2 diabetes, fatty liver disease, cardiovascular disease and cancer. These inter-related diseases reduce life expectancy and their treatments come at an enormous financial cost. The overriding aim of this work is to understand the molecular and cellular regulation of lipid metabolism in skeletal muscle, liver and adipose tissue, and how this impacts endocrine function to affect the pathogenesis of types 2 diabetes and prostate cancer.
Pattern Recognition Receptors In Inflammation And Infection
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Innate immunity provides our first line of defence against infections, but pathogens can overcome this system. Understanding how microbes disable innate immunity can teach us how to prevent and/or treat infectious diseases. Innate immunity acts by initiating inflammation. Many important acute and chronic diseases develop when this process is dysregulated. Blocking innate immunity thus has potential to treat many diseases. This project aims to understand innate immunity in these contexts.
Most common diseases of ageing like diabetes and cancer have proven intractable because much of our knowledge is limited to individual molecules. This proposal takes a global approach to complex diseases, utilising quantitative high-resolution methods and computational modelling. This research will lead to a completely new way of thinking about complex diseases providing a range of completely novel treatment options.
In patients predisposed to metabolic diseases, excessive fats get delivered to various tissues. About 10 to 15% are converted into sphingolipids, many of which have deleterious effects on tissue function. Blocking sphingolipid production prevents diabetes and most cardiovascular diseases in rodents. We seek to better understand these mechanisms and determine how the observations can be translated into new therapies and better clinical outcomes.
The Molecular Basis By Which IL-6 Family Cytokines And Pathogen Recognition Receptors Promote Inflammation-associated Stomach And Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Lung and stomach cancer are the 2 most lethal cancers world-wide, and represent a growing number of cancers associated with chronic inflammation. However, the genes which trigger inflammation and then promote cancer in certain people remain largely unknown. Using mouse models for these inflammation-associated cancers, together with clinical specimens, our aim is to identify specific genes of the immune system which trigger chronic inflammatory responses that lead to cancer.
Diabetes And Obesity: From Benchtop To Public Health
Funder
National Health and Medical Research Council
Funding Amount
$705,501.00
Summary
Obesity. Novel factors, not related to food intake or physical activity, will be explored as possible causes of obesity. The obesity paradox, in which overweight is associated with reduced mortality, will be examined. Diabetes treatment. Methods will be developed to predict which is the right drug for each individual patient. A study will test the use of nurse-led clinics. A novel insulin delivery mechanism will be developed. Novel causes and consequences of diabetes will be explored.
Pancreatic Islet Inflammation And Its Role In Diabetes And Islet Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
Diabetes is a major health epidemic & diabetic complications are a major cause of morbidity and mortality in our community. My studies have increased our understanding of how inflammation contributes to diabetes but also directly led to the discovery of novel therapies that are been trialed in patients with type 1 diabetes undergoing islet cell transplants. My studies have increased our knowledge of the factors that lead to type 1 diabetes and the development of new treatments.
I am the leading scientist studying a factor named BAFF and discovered its role in autoimmunity. BAFF inhibitors are effective in late stage clinical trials treating lupus patients. Our new work shows that BAFF has other fascinating roles, in particular the ability to control effects from some microbes capable of activating autoimmune and inflammatory reactions. This new work is leading us to the development of an entirely new generation of therapeutics treating autoimmunity and inflammation.
Toll-like Receptors And Innate Immunity: Genes And Pathways Regulating Infectious And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$138,367.00
Summary
The innate immune system is the first line of defence against infectious diseases, but also contributes to the pathology of inflammatory diseases (e.g. rheumatoid arthritis). I study specific genes and pathways used by the innate immune system to (1) understand how the innate immune system prevents infections and how microorganisms overcome these defences, and (2) develop approaches to block inflammation. Outcomes may include new therapies for inflammatory and infectious diseases.
This research aims to advance my novel discoveries of mechanisms through which hormones and enzymes control and coordinate optimal female fertility. The findings are being applied to novel technologies in reproductive medicine. This work further aims to characterize mechanisms of growth and metastasis in reproductive organ cancers. New diagnostics and therapeutics for patients with metastatic reproductive cancers are arising from this research.