Investigating The Dynamic Interactions Between Immune And Cancer Cells Using Two-photon Intravital Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therap ....Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therapeutic approaches.Read moreRead less
Inhibiting Tumour Growth By Targeting EphA3 And Disrupting Tumour Stromal And Vascular Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$645,136.00
Summary
Tumours consist of cancer cells, tumour blood vessels and connective tissue, all of which are different to normal tissues. Many of the cells making up tumour vessels and connective tissue are recruited, during initial growth and subsequent spreading of tumours, from the bone marrow. Our research will examine the presence and function of the EphA3 receptor on these cells during tumour development and assess how our anti-EphA3 antibody inhibits tumour growth by targeting stroma and vasculature.
Targeting Homeobox Genes In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$658,739.00
Summary
Acute myeloid leukaemia (AML) is a common blood cancer with dire clinical prognosis due to a lack of targeted molecular therapies. In this proposal we will identify new ways of targeting transcription factor proteins that are overexpressed in AML and promote leukaemia by repressing normal cellular growth controls. This may lead to novel methods to target leukaemic stem cells to specifically eliminate myeloid leukemia
Genomic Analysis Of The Novel Epigenetic Modifier Smchd1 As A Tumour Suppressor
Funder
National Health and Medical Research Council
Funding Amount
$619,142.00
Summary
Epigenetic modifications are changes made to our DNA that act like punctuation marks in the genome, to instruct the cell when to turn genes on and when to switch them off. Epigenetic control is critical to range of different biological processes, and also goes awry in cancer. We are specifically interested in the role of one new protein involved in epigentic control and characterising its role as a tumour suppressor.
My research projects in the fields of cancer biology, vascular biology and immunology assess molecular mechanisms of vascular remodelling and implications for disease.
Examination Of The Mechanism By Which The Salvador/warts/hippo Complex Restricts Cell Growth And Number
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
Cancer is a disease that results from the generation of surplus cells. These extra unwanted cells are produced as a result of excess cell proliferation and impaired programmed cell death. These important processes can be deregulated in cancers as a result of mutations in many different genes. Many genetic lesions have been reported in different types of cancers but many of the genes that are mutated in these diseases have yet to be identified. To isolate new genes involved in cancer we created r ....Cancer is a disease that results from the generation of surplus cells. These extra unwanted cells are produced as a result of excess cell proliferation and impaired programmed cell death. These important processes can be deregulated in cancers as a result of mutations in many different genes. Many genetic lesions have been reported in different types of cancers but many of the genes that are mutated in these diseases have yet to be identified. To isolate new genes involved in cancer we created random mutations in the vinegar fly, Drosophila, and tested their ability to cause solid cancers. Drosophila is an excellent model organism for this study because many of the pathways that are often perturbed in cancer are conserved between humans and flies. Using this approach we identified several known and novel genes that cause cancerous growths. By studying the human counterparts of these novel genes we identified a potential role for some of these genes in the generation of human cancer. Three of these genes, hippo, salvador and warts, appear to act in concert to restrict cell number. In this study we aim to understand the mechanism by which these genes restrict cell number. To do this we will analyze how the activity of this pathway is controlled and in what tissues it functions. We also plan to discover other key components of this pathway that function downstream of hippo, salvador and warts. To perform these experiments we will use a variety in vitro biochemical techniques as well as experiments in tissue culture cells. We will then verify the results of these experiments in the context of a whole animal. By performing these experiments we hope to gain greater insight into the genesis of cancer.Read moreRead less
Investigating Immune Regulation In The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
Suppressive factors made by cells of the immune system or cancers themselves and immune regulatory T cells inhibit an effective anti-tumour response. My project aims to investigate the mechanism by which these factors and cells mediate their suppressive function. Understanding these processes in the cancer environment will allow the design of more effective cancer therapies.
Prediction Of Clinical Radiosensitivity Caused By Ionising Radiation During Radiotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation bio ....Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation biology research is to develop efficient predictive measures that could identify radiosensitive individuals prior to treatment. This predictive ability would enable the individualisation of radiotherapy radiation doses, which should result in improvement of tumour control rates and a reduction in the incidence of side effects associated with radiotherapy. We aim to understand radiosensitivity at the molecular level using the powerful technology of microarrays. Using microarray technology, thousands of genes can be tested for expression activity simultaneously. We have a unique tissue bank established from many radiosensitive and non-sensitive control radiotherapy patients. The use of microarray technology on samples from this unique tissue bank may enable the gene expression pattern of individuals that display radiosensitivity to be distinguished from the rest of the population. In conjunction, two additional tests will be used to determine who is susceptible to radiosensitive reactions which include assessment of a DNA repair pathway and assessment of the length of the telomeres (Caps on the ends of the chromosomes), both of which have been shown to be involved with radiosensitivy. This experimentation will hopefully lead to the development of a predictive assay for use in the clinic for cancer patients prior to receiving radiotherapy.Read moreRead less