Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.
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
Molecular Pathways Mediating The Anti-tumour Activity Of WIF1
Funder
National Health and Medical Research Council
Funding Amount
$462,342.00
Summary
Osteosarcoma is the most common bone cancer. Treatment often entails aggressive surgery with intensive chemotherapy, although one third of those diagnosed will still die from this disease. We have found that the molecule WIF1 can suppress osteosarcoma growth. In this project we aim to identify genetic modifiers of WIF1, potential WIF1 interactors and define active domains of WIF1 for the development of more effective targeted therapeutics for osteosarcoma.
Definition Of The Role Of Senescence In Tumour-associated Endothelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$583,081.00
Summary
'Cellular senescence' is a mechanism to stop cells growing, and it may protect against tumour growth. However, it may also induce changes in cells leading to 'pro-tumour' effects. We have identified a gene - which we have called SEN1 - which induces senescence in the blood vessels of tumours. This gene may cause alterations in the blood supply to the tumour allowing it to grow and to resist chemotherapy. Understanding this gene may allow us to treat cancer by shutting off its blood supply.
Identification And Targeting Of A Potent NK Cell “checkpoint” In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitizes NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells become hyper-activated and prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy
Enhanced Translation Of Epstein-Barr Virus Nuclear Protein, EBNA1, As A Target Fot T Cell-based Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Epstein-Barr virus, (EBV) is a human herpesvirus associated with a range of human cancers. EBNA1, an important EBV antigen, was thought to be “immunologically silent” however, recent studies from our laboratory show that EBNA1 is recognized by our body's defence system and these observations raise the possibility that EBNA1 may be an exploitable, immuno-therapy target for treating EBV-associated cancers.
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.Read moreRead less
Every cell in our body has an intrinsic orientation that is controlled by a universal set of genes known as polarity genes. Loss of this orientation is a common and early feature of cancer. We have identified the gene Scribble as a gene that controls cell orientation and is essential to prevent the development of prostate cancer. We propose experiments to discover how Scribble controls prostate cancer and whether it can be used to better predict outcome for prostate cancer patients.
Using Connective Tissue Stem Cells To Treat Human Disease.
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
In our recent Cell paper (January 15, 2015), we reported our discovery of two new adult stem cells. One of these, the osteochondroreticular (OCR) bone stem cell (pronounced “ocker” stem cell) has a particular affinity for developing cartilage. We are testing if this cell could be used as a new treatment for osteoarthritis. The second new stem cell we discovered, is called the iRSC, and lies within the intestine. We are studying this cell in the development and treatment of bowel cancer.