The Distinctive Roles Of Tissue Transglutaminase Isoforms In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Neuroblastoma caused by N-Myc oncogene accounts for about one third of the disease and represents a more aggressive subtype with a worse clinical outcome. This project aims to identify factors responsible for N-Myc-induced neuroblastoma initiation and factors sensitizing neuroblastoma cells to anti-cancer drugs, and to provide the basis for clinical trials of a combination therapy in children with neuroblastoma.
Targeting Histone Deacetylases For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,513.00
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 proteins called histone deacetylases promote cancer initiation and progression, and whether combination therapy with an inhibitor of the histone deacetylases and another anti-cancer agent exert efficient synergistic anti-cancer effects in animal models of neuroblastoma and pancreatic cancer.
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.
A Phase II Study Of Continuous, Low-dose LBH 589 (Panobinostat) In Patients With Refractory Solid Tumors, Including CNS Tumors
Funder
National Health and Medical Research Council
Funding Amount
$811,512.00
Summary
Research done recently across three separate Australian laboratories has shown great promise with a new anti-cancer drug LBH589 used for cancers in children and young adults. We wish to start a clinical trial of LBH589 in children and young adult patients with cancer.
Targeting The Class IIa Histone Deacetylases In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Dysfunctional metabolism in skeletal muscle is integral in the development of metabolic diseases, such as obesity and type 2 diabetes. This project will examine proteins that alter the way genes are expressed for their role in dysfunctional metabolism in muscle. This project could uncover new therapies for the treatment of metabolic diseases.
Regulation Of Macrophage Gene Expression And Function By Histone Deacetylases
Funder
National Health and Medical Research Council
Funding Amount
$35,909.00
Summary
Macrophages are white blood cells that play a major role in the development of inflammatory diseases such as rheumatoid arthritis and atherosclerosis, diseases that are a major burden to Australian society. This project aims to characterise the effects of a novel class of potential anti-inflammatory agents on macrophages. Defining how these drugs modify macrophages in disease models will allow design of therapeutics with minimal side effects.
Importance Of Histone Variant H2AZ Acetylation In Gene Activation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,737.00
Summary
DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel canc ....DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel cancer therapeutic target.Read moreRead less
Targeting Histone Deacetylases 1 And 5 To Reduce Inflammation And Bone Loss In Periodontitis.
Funder
National Health and Medical Research Council
Funding Amount
$536,745.00
Summary
Bone loss and tooth loosening are serious complications in periodontitis. Despite the prevalence of this disease current treatments do not directly stop the bone loss. Our recent laboratory studies show inhibiting histone deacetylase (HDAC) activity with very low doses of inhibitors can effectively suppress this bone loss in periodontitis. This project aims to investigate specific targeting inhibitors of HDAC 1 and HDAC 5 to treat periodontitis by enhancing bone formation and reducing bone loss.
Reprogramming Innate Immunity To Combat Inflammatory And Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$1,788,220.00
Summary
Our immune system protects us from infection, but also drives cancer, autoimmune diseases, inflammatory diseases and many other conditions. Innate immunity, a key component of our immune system, mediates the pathology that is associated with these diseases. This research program aims to define innate immune mechanisms that combat infection and/or drive inflammation-mediated diseases. It also aims to deliver novel anti-infective and anti-inflammatory strategies.