New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
Phagocytic Clearance And Immune Activation In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Macrophage white blood cells clear malaria infected cells by eating them, by three routes- by recognising ANTIBODIES or COMPLEMENT on the cell surface, or by the cell BINDING directly to the macrophage. Each has different results, such as amounts of cytokines produced. Cytokines clear malaria; in excess they can cause fatal immune pathology. We will investigate how variations in amount of antibody and complement and route of uptake of malaria infected cells might determine malaria outcome.
Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Determinants Of Sustained Virological Response After Discontinuation Of Long-term Nucleoside Analogue Therapy In Chronic Hepatitis B Patients
Funder
National Health and Medical Research Council
Funding Amount
$976,778.00
Summary
Guidelines currently recommend lifelong treatment for patients with chronic hepatitis B, with associated cost and risks of drug resistance and side effects. It has recently been suggested that up to 50% of patients may safely and successfully stop drug after long-term treatment. Our project will identify which patients can safely stop treatment, by performing detailed studies of the human immune system and the hepatitis B virus. This will be an important advance for patient care.
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.