The Role Of RYK And Eph Receptors In Developmental And Tumour Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
The formation of blood vessels (angiogenesis) is a key process in development of the embryo, wound healing, tumour formation-metastases and in the re-vascularisation of ischeamic limbs. The molecules which control these processess are slowly being characterised. In general belong to a family of molecules called growth factors and theri associated receptor present on the surface of a cell. These molecules can control the number, location and function of specific blood vessels within the body. Rec ....The formation of blood vessels (angiogenesis) is a key process in development of the embryo, wound healing, tumour formation-metastases and in the re-vascularisation of ischeamic limbs. The molecules which control these processess are slowly being characterised. In general belong to a family of molecules called growth factors and theri associated receptor present on the surface of a cell. These molecules can control the number, location and function of specific blood vessels within the body. Recently we have discoverd new members of a family of growth fcators called vascular endothelial growth factors, and demonstrated their ability to promote the growth of blood and lymphatic vessels. In this study we set out to examine the role of another family of growth factor receptors, called RYK (for which we have a granted patent in the USA and Australia) in angiogenesis. functional experiments in mice have demonstrated that RYK can associated with a family of receptors called Eph receptors which play a key role in the remodelling of blood vessels during development and injury. Studying these molecules may tell us why blood vessels know' to be in the correct locations in the body and why in certain disease we see vessels of incorrect structure or location. These studies will form a basis of knowledge to develop rational means to manipulate blood vessel formation in the body, using non-surgical methods. The work will also have application to the areas of cleft palate, craniofacial abnormalities and axon pathfinding.Read moreRead less
Strategies To Enhance Recruitment Of Hematopoietic Stem Cells And Their Differentiation To Retinal Pigment Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$29,627.00
Summary
Age-related macular degeneration (ARMD) is the leading cause of adult blindness in the western world. As the Australian population ages, many more people will suffer from this disease. This project aims to use adult stem cells, called hematopoietic stem cells (HSC) to repair injured vessels in the eye. This approach optimises healthy repair of the retina by facilitating differentiation of HSC into retinal pigment epithelium, the cells whose malfunction is the underlying initiator of the disease.
Translating Molecular Pathology Into Cancer Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$479,882.00
Summary
The aim of this research is focussed on translation of basic science through to the clinic by introducing novel cancer diagnostics and technologies. Other integral aims are to identify new changes in DNA and other cancer cell markers in patients, assess the clinical utility of these as biomarkers (surrogates of cancer behaviour) and to conduct novel clinical trials with newly identified molecular targets of cancer and new therapeutics and combinations to assess their efficacy.
Development Of Anti-CXCR2 Monoclonal Antibodies For Tumour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$174,867.00
Summary
New therapies to treat cancers and inflammatory diseases are urgently required. Our aim is to develop a new treatment for cancer and inflammation, by blocking the chemokine receptor CXCR2 which is central to angiogenesis (blood vessel growth) and inflammation. We have produced a highly effective monoclonal antibody (mAb) inhibitor of CXCR2, that is suitable for preclinical and clinical development. The project aims to examine the efficacy of this mAb in mouse tumour models and inflammation.
Modulating Skin Regenerative Responses To Improve Wound Repair And Fight Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Skin disorders, such as hard to heal wounds or the most common skin cancers, are a major burden on the national health system. Despite their different nature they employ similar mechanisms of response to injury. In this project we intend to develop a comprehensive understanding of the genetic and molecular mechanisms at play to allow clinical interventions to prevent or to cure these disorders.
Understanding The Molecular Pathways That Determine Response To Anti-angiogenic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$209,539.00
Summary
Anti-angiogenesis is an important new approach to treat conditions such as cancer and eye disease. Our study is designed to understand the molecular pathways that lead to patients either being or developing resistance to these treatments. Using advanced cell and molecular biology techniques we will identify ways in which the blood vessels evade these therapies. Once identified these molecules will provide additional targets for developing therapeutics and diagnostics.
GENETIC MANIPULATION OF TUMOURS TO INDUCE IMMUNE REJECTION
Funder
National Health and Medical Research Council
Funding Amount
$396,342.00
Summary
The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expr ....The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expressed in tumour cells will induce protective immune responses against the tumour (ii) to investigate the effectiveness of combination approaches to gene therapy whereby genetic manipulations which cause destruction of tumour cells, or inhibition of blood vessel growth in tumours can be combined with administration of immunologically relevant genes to enhance tumour destruction (iii) to identify molecules which can act as target tumour antigens for the immune response or which are involved in promoting tumour survival so that these genes may be manipulated to enhance the development of anti-tumour immunity. The model we will use to investigate these issues will be malignant mesothelioma (MM). This tumour type is currently untreatable and is resistant to all available forms of therapy. Achievement of the aims described above would lead to the capacity for early treatment of MM. The identification of suitable target antigens has the potential to lead to vaccination protocols for therapy or as a preventative measure. Furthermore, the principles defined in this project will be applicable to the treatment of a variety of other solid tumours which are currently resistant to conventional therapy.Read moreRead less
Can Esomeprazole Improve Outcomes In Women At High Risk Of Pre-eclampsia? A Phase II Placebo-controlled Randomised, Multi-centre Clinical Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,597,125.00
Summary
Pre-eclampsia, recognised through the development of high blood pressure in pregnancy, causes death and/or injury to mothers and babies. An improved understanding of the development of pre-eclampsia has provided opportunities for early prediction and prevention of disease. We will use a powerful predictive model to identify pregnancies at high risk of pre-eclampsia then observe the effect of a novel treatment (esomeprazole) on maternal blood pressure and the development of this disease.
Receptor Tyrosine Kinase Function As Molecular Target In Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$415,788.00
Summary
As molecular cell biologist and protein chemist my motivation for research is to tackle metastatic cancer, one of the principle health burdens of the 21 century. Over the next five years I will lead R&D programs with national and international collaborators that will generate new diagnostic approaches and insights in basic and translational research. These will allow us to develop anti-cancer drugs, which target several of the mechanisms that are active in metastatic cancers.