Exploiting The Pharmacokinetic And Pharmacodynamic Properties Of Bile Acid Receptor Agonists To Treat Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$653,952.00
Summary
We have generated preliminary data suggesting that chemicals made by the liver, called bile acids, act on fat cells to release a hormone called adiponectin. In liver disease adiponectin has favorable effects, including reducing liver inflammation and fibrosis (scarring). By using drugs that mimic the action of bile acids we expect that adiponectin production by fat cells can be increased, creating a new way to treat patients with chronic liver diseases.
Molecular & Translational Characterisation Of IMiD-Mediated BET-Protein Degradation In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$497,857.00
Summary
Thalidomide-like drugs (called IMiDs) are an essential treatment for multiple myeloma, a common incurable blood cancer. We have discovered that IMiDs destroy proteins that myeloma cells use to ‘read’ cancer-causing genes in their own DNA. We will therefore investigate how important the destruction of these ‘gene readers’ is in myeloma cells, including patient samples. This will set up future studies targeting ‘gene readers’ using IMiDs in combination with other targeted drugs in clinical trials.
Identifying And Preventing The Epithelial Triggers Of Neutrophilic Inflammation In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$961,124.00
Summary
We have identified aberrant immune responses to viruses and bacteria as potential triggers of damaging airway inflammation soon after children are diagnosed with cystic fibrosis after newborn screening. We will investigate the mechanisms underlying these responses and develop therapies with the potential to reduce inflammation and prevent lung disease.
Nanomedicine Targeted Delivery Of Therapeutics To The Placenta To Treat Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$513,148.00
Summary
Preeclampsia, one of the most serious complications of pregnancy, affects around 3-8% of all pregnancies. Sadly, there is no treatment. We have developed a new technique to deliver treatments only to the placenta, sparing the mother and baby from side effects. We will test whether this technique can treat the source of preeclampsia, the placenta, in human and mouse models in our laboratory. This work has potential to offer possibilities of new treatments to other pregnancy complications.
Targeting The Histone Methyltransferase DOT1L For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,127.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Pancreatic cancer is the fourth leading cause of cancer death in adults. In this application, we will define how a protein called histone methyltransferase DOT1L promotes cancer initiation and progression, and whether inhibitors of the histone methyltransferase DOT1L exert efficient anti-cancer effects against neuroblastoma and pancreatic cancer.
MPO-ANCA GN is a major cause of renal failure. Current treatments are toxic and poorly effective. Excessive DNA production resulting in prominent deposits of extracellular DNA are seen in glomeruli of patients with MPO-ANCA GN. This study will look at the pathological role of DNA and in a relevant animal model, use DNase I treatment to dissolve deposited DNA and treat anti-MPO autoimmunity and GN. This evidence will allow the introduction of DNase I in clinical trials.
Plasma Exchange And Glucocorticoids In Anti-neutrophil Cytoplasm Antibody Associated Systemic Vasculitis: A Randomised Controlled Trial (PEXIVAS Australia)
Funder
National Health and Medical Research Council
Funding Amount
$420,110.00
Summary
ANCA-associated vasculitis is a life-threatening disease. The PEXIVAS trial will investigate whether plasma exchange, in addition to immunosuppressive therapy and glucocorticoids, will reduce death and the development of severe kidney failure due to this disease. Additionally, the project will also look at whether using a reduced dose of glucocorticoids is just as effective as larger doses in lessening the infectious complications of treatment.
Hookworm Therapy In Coeliac Disease (CeD), Phase 1b
Funder
National Health and Medical Research Council
Funding Amount
$865,002.00
Summary
Parasitic worms have an amazing ability to manipulate the immune system, and our research group recently discovered how they may hold the key for treating inflammatory diseases such as Coeliac Disease. The aim of my research is to further develop this novel therapy in a clinical trial and study the mechanism of how worms control the immune response, including identifying the molecules that the worm produces that could be produced as a pill-based medication for treating coeliac disease.
UNDERSTANDING THE MOLECULAR MECHANISMS CONTROLLING NUCLEOLAR SURVEILLANCE IN DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$855,972.00
Summary
Alterations in the ability of cells to make ribosomes, the cellular factories that make protein, contribute to a range of diseases including cancer and a class of inherited disorders called ribosomopathies that are rare but largely untreatable. These changes cause disease by controlling the “nucleolar surveillance pathway” that causes cells to either stop dividing or die. Here we propose to identify new genes that regulate this pathway to identify new targets for treating these diseases.