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.
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.
Understanding The Role Of Class IIa Histone Deacetylases In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$469,779.00
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.
Targeting JMJD6 Gene Gain For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$381,012.00
Summary
Cancer is the most common cause of death from disease in children. Neuroblastoma is the most prevalent solid tumour in early childhood. In this project, we will define the key role of JMJD6 gene gain in neuroblastoma cell proliferation, survival and tumourigenesis. We will also identify a novel therapeutic strategy for the treatment of neuroblastoma.
Defining The Apoptotic And Therapeutic Activities Of Histone Deacetylase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$694,627.00
Summary
HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have used a mouse model of human blood cancers to show that these inhibitors can be used safely to severely limit the growth and spread of blood cancers. HDACi have the ability to inhibit multiple different target proteins (HDACs) and we aim to identify the key HDACs that cancer cells require to remain viable. Such information will lead to a more targeted or rational ....HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have used a mouse model of human blood cancers to show that these inhibitors can be used safely to severely limit the growth and spread of blood cancers. HDACi have the ability to inhibit multiple different target proteins (HDACs) and we aim to identify the key HDACs that cancer cells require to remain viable. Such information will lead to a more targeted or rational approach to chemotherapy using HDACi.Read moreRead less
Identification And Characterization Of A Novel Long Intergenic Noncoding RNA For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Survivors suffer from lifelong disabilities due to chemotherapy. In this application, we will define the role of gene amplification of a long intergenic non-protein-coding RNA in determining the biological effects of a neuroblastoma oncogene, and promoting neuroblastoma initiation and progression. We will also define the anti-cancer efficacy of therapies targeting the long intergenic non-protein-coding RNA.
The Role Of GAPDH Acetylation And HDAC6 In Liver Metabolism And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$635,428.00
Summary
Type 2 diabetes (T2D) is characterised by persistent elevated blood glucose levels. Altered liver metabolism is a key contributor to elevated blood glucose levels in T2D, through uncontrolled synthesis and release of glucose. This project will examine whether regulation of a metabolic enzyme called GAPDH by a process termed acetylation, contributes to normal liver glucose metabolism. This project will also assess whether altered GAPDH acetylation contributes to hyperglycaemia in T2D.
Combating Infectious Diseases By Harnessing Macrophage Functions
Funder
National Health and Medical Research Council
Funding Amount
$688,152.00
Summary
Infectious diseases present a persistent global health threat. For patients with life-threatening diseases caused by bacterial pathogens, antibiotics provide the last resort. Antibiotic resistance, even for newly developed antibiotics, is widespread within the bacterial community. New strategies are urgently needed to combat most bacterial infections. This proposal will investigate a new strategy to train and boost our immune systems to combat infectious diseases.