Promoting Intestinal Stem-cell Mediated Regeneration Following Damage: A Critical Role For Neuregulin 1
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Diseases, infections and pathologies are common clinical problems of the intestine in humans that can lead to loss of intestinal tissue. Individuals with these conditions can experience nutritional problems and severe cases result in death. Promoting regeneration of the damaged tissue is critical to re-establish intestinal function. In this study, we will examine the regenerative potential of a growth factor called Neuregulin1 in the intestine with the aim of facilitating tissue regeneration.
SETD7-dependent Regulation Of Hippo/YAP And Wnt/beta-catenin Pathways In The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Colon cancer accounts for approximately 10% of all cancer-related deaths in Australia. One of the most common causes of colon cancer is a mutation in a signalling pathway called the Wnt/beta-catenin pathway. Despite this knowledge, there are currently no drugs that directly target this pathway to treat colon cancer. We have now identified a new way to control this pathway and have developed a potent and specific drug to block activation of this pathway.
Epigenetic And Functional Decline Of Intestinal Stem Cells During Aging
Funder
National Health and Medical Research Council
Funding Amount
$584,390.00
Summary
Age related changes have been shown to impact on the overall functional properties of the intestinal epithelium, which affects overall nutrition and quality of life in the aged population. This proposal will study the cellular and molecular mechanisms underlying intestine deterioration during aging.
Deciphering The Overlapping Roles Of SSB1 And SSB2 In The Regulation Of Haematopoiesis And Intestinal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$996,631.00
Summary
Our work centres on elucidating the role of two newly identified and related single-stranded DNA binding protein (Ssb1 and Ssb2) in development of blood and gut system. When both genes are deleted mice die with 8 days of knockdown due to bone marrow failure and intestinal atrophy. Our double knockout model parallels the consequences of radiation damage on blood and gut system. Toxicity to these systems is a significant hindrance in delivering anti-tumor therapy.
DOES BCL-G, A BH3-ONLY PROTEIN, PLAY A ROLE IN INFLAMMATION-ASSOCIATED COLON CANCER?
Funder
National Health and Medical Research Council
Funding Amount
$418,587.00
Summary
Deregulation of the function of several members of the Bcl-2 family has been shown to be an aggravating factor in autoimmune diseases and cancer. Bcl-G is a new and poorly characterized member of this family. We have produced essential tools to study the physiological function of Bcl-G, and discovered that it plays a role in inflammatory bowel disease. We now plan to investigate its possible role in inflammation-associated colon cancer.?
Role Of Snail Proteins In Mediating Intestinal Stem Cell Identity
Funder
National Health and Medical Research Council
Funding Amount
$646,698.00
Summary
The lining of the intestine is constantly renewed by stem cells which also contribute to replenishment of this layer following damage caused by trauma, infection or treatments such as chemotherapy. We are studying how a family of gene regulators called Snail proteins act to maintain stem cells in the gut. Snail proteins have also been found to be present at high levels in bowel tumours so we are examining their role in the genesis of tumours and resistance to common treatments.
Mediator Kinase As A Therapeutic Target For Wnt/β-catenin Dependent Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$949,907.00
Summary
Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy ....Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy.Read moreRead less
Interleukin 37 – A Novel Cytokine Therapy For Necrotizing Enterocolitis In The Preterm
Funder
National Health and Medical Research Council
Funding Amount
$748,848.00
Summary
Neonatologists are adept at keeping extremely premature babies alive. But the price is a rising incidence of life-threatening diseases that include necrotising enterocolitis (NEC), a progressive and destructive intestinal inflammation that may require surgery, after which just 30% survive. We have created highly potent variants of the anti-inflammatory molecule interleukin 37 whose actions will improve our understanding of NEC pathogenesis and reveal their therapeutic potential in NEC.
Use Of A Novel Technique To Identify The Sensory Nerve Endings That Respond To Painful Stimuli In The Upper Gastrointestinal Tract And Characterize Their Mechanisms Of Activation
Funder
National Health and Medical Research Council
Funding Amount
$353,243.00
Summary
Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characte ....Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characterise the mechanisms underlying their activation.Read moreRead less
Understanding How Inflammatory Bowel Disease Causes Hypersensitivity Of Colonic Sensory Nerve Endings And Increased Abdominal Pain
Funder
National Health and Medical Research Council
Funding Amount
$589,466.00
Summary
Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inf ....Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inflammation to cause increased abdominal pain.Read moreRead less