We have identified a novel gene, Inpp5e, that when mutated causes a disease similar to Joubert syndrome and MORMS disease which leads to abnormal movements, developmental delays, mental retardation, abnormal breathing and eye movement. We have identified a candidate gene for these diseases and have shown that deletion of this gene in mice results in similar pathology. We aim to determine the mechanism by which Inpp5e regulates human development and disease.
Ciliopathies are an emerging group of syndromes in society that have devastating health effects. Ciliopathy patients exhibit a specturm of disorders including polycystic kidneys, extra digits, retinal degeneration and neural tube defects. INPP5E is a gene that is mutated in patients with a ciliopathy syndrome. These studies will determine the role of INPP5E in ciliopathy disease and may identify INPP5E as a novel treatment target.
Fibrosis is a key cause of renal pathology-dysfunction. Relaxin is an endogenous reno-protective factor, and thus has enormous therapeutic potential. However, despite compelling pre-clinical evidence of its efficacy, little is known about relaxin's mechanism of action. These studies will lead to a much better understanding of its signal transduction properties that will allow us to maximise its anti-fibrotic potential; identify new targets for intervention; and design better clinical trials.
This project aims to comprehensively evaluate the role of androgen receptor (AR) signalling in breast cancer by identifying changes in AR signalling and its role in an endocrine resistant setting. Understanding the changes in AR signalling in either treatment-naive or treatment-resistant context would better assist in the identification for opportunities to modulate AR signalling as a therapeutic target in breast cancer.
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.
Overcoming Therapeutic Resistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$924,901.00
Summary
Pancreatic cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth and metastasis. In particular, we will test whether cytokine inhibitors can overcome tumour resistance to chemotherapy.
Cancer causes significant morbidity and mortality in Australia’s aging population. There is strong evidence that abnormal blood vessels in tumours limit drug access and drive metastases. We have identified a molecule which controls vessel remodelling in tumours. In this proposal we will study mechanisms on how the molecule itself is regulated with the aim to normalize blood vessels for improved therapy.
Identifying Novel Genome Instability Signatures In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is the single biggest clinical problem facing the world. An underlying hallmark of cancer is the accumulation of errors in the genetic information of a cell which arises through genomic instability. This research project aims to investigate novel molecules identified by our screening that function in response to genomic instability in cancer. This study is expected to define roles for each molecule in the maintenance of genomic stability and predict for patient diagnosis and outcome.
Understanding The Role Of The IL11-Stat3-Th17 Signaling Axis In Gastrointestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,743.00
Summary
Gastrointestinal cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth. In particular, we will explore the role of a cytokine called Interleukin-11 in these processes to identify novel cancer therapies.
Investigating The Cellular Requirement For STIM1 Phosphorylation And Store-operated Calcium Entry Suppression During Mitosis: Roles In Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$344,900.00
Summary
Cells are constantly interacting with and modifying their surrounding environment. The intracellular calcium signal is one mechanism cells use to translate signals from the microenvironment into cellular responses. This proposal seeks to explore why a key calcium signalling pathway, known as store-operated calcium entry, is specifically silenced during cell division, and to determine how reversing this inhibition affects cell division during normal development and in cancer.