EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
Therapeutic Potential Of Inhibiting Eph/ephrin Signalling To Repair The Vascular Endothelium In Septic Shock
Funder
National Health and Medical Research Council
Funding Amount
$664,734.00
Summary
Septic shock is a life-threatening condition usually caused by bacterial infection in the bloodstream. More than 5000 people, including 500 children, die from sepsis each year in Australia. Worldwide, it is the most significant cause of death in children. Sepsis is associated with leakage of fluid and proteins through the cells lining the blood vessels. This project will develop and test a novel treatment for sepsis which focuses on reducing this leakage by blocking the Eph/ephrin proteins.
Mesenchymal Stem Cell Maintenance And Recruitment During Skeletal Repair Are Dependent On EphB-ephrinB Signalling
Funder
National Health and Medical Research Council
Funding Amount
$611,827.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
EphA3, A Novel Target For Leukaemia Stem Cell Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,992.00
Summary
Patients with acute myeloid leukaemia often respond to therapy, but many relapse due to “leukemic stem cells” (LSC), the few cells in the original leukaemia which survive therapy. We focus on a protein (EphA3) which sits on LSCs and helps them interact with their environment. Disrupting this interaction may make these cells vulnerable to therapy. We aim to determine the function of EphA3 on LSCs and optimise the therapeutic use of an antibody against EphA3 which is currently in clinical trial.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
Leukocyte Immunoglobulin-like Receptors Regulate The Function Of The Major Cells Involved In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
An important aspect of the immune system is its ability to maintain a delicate equilibrium between the extremes of reactivity and quiescence. A break in this equilibrium can lead to unchecked activation of immune cells or inability of these cells to mount an effective defence. Potential outcomes of the unchecked activation of cells are autoimmune diseases such as rheumatoid arthritis or allergic diseases such as asthma. A new family of cell surface proteins termed leukocyte immunoglobulin-like r ....An important aspect of the immune system is its ability to maintain a delicate equilibrium between the extremes of reactivity and quiescence. A break in this equilibrium can lead to unchecked activation of immune cells or inability of these cells to mount an effective defence. Potential outcomes of the unchecked activation of cells are autoimmune diseases such as rheumatoid arthritis or allergic diseases such as asthma. A new family of cell surface proteins termed leukocyte immunoglobulin-like receptors (LIRs) has been shown to regulate immune cells by either increasing or decreasing their activity. In this project we will study the role of LIRs in regulating the activity of the major cells involved in allergy and asthma. This study would provide important insights to mechanism(s) of regulation of immune cell activation during protective immune responses such as the fight against infections and cancers and during pathological inflammations such as asthma and rheumatoid arthritis. Understanding the role of the LIRs in the regulation of immune cell activation might lead to new therapeutic strategies aimed at restoring the balance between the inhibitory and activating LIRs.Read moreRead less
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.