Clinical And Microbiological Predictors Of Post-operative Crohn's Disease Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change internat ....The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change international practice.Read moreRead less
Muc1 Regulation Of The NLRP3 Inflammasome In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
The mucin Muc1 is an important part of the barrier against infection in the gut, and appears to protect against development of bacterial inflammatory disease. We have identified that Muc1 suppresses activation of the inflammasome (a mechanism by which pathogens cause inflammation). We will now examine how Muc1 does this and explore the importance of this effect on inflammatory disease in the intestine. This may identify novel approaches for protecting against gastric and colorectal cancer.
Prof Kamm is a gastroenterologist interested in developing improved treatments for gastrointestinal and pelvic floor disorders, such as inflammatory bowel disease and functional disorders. He runs basic science, translational and clinical strands of research in parallel across the same areas of interest, developing new treatments that encompass physiological, pharmacological, surgical and psychological therapies.
The CpG Island Methylator Phenotype In Colorectal Cancer - Pathways And Precursors
Funder
National Health and Medical Research Council
Funding Amount
$517,272.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four differen ....Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four different subgroups of bowel tumours, and that each of these may have different physical properties and responses to therapy. We aim to better characterise these subgroups to increase our understanding of how normal bowel can change into a small polyp, that may grow into a cancer. Understanding the gene changes leading to each subtype of bowel cancer will in the future allow the development gene markers for early detection as well as the possibility of individualised patient therapy. We are also studying tiny biopsies of normal bowel tissue from patients either with or without polyps, to try to understand the very earliest changes which may underly the development of a bowel polyp.Read moreRead less
KRAS- And BRAF-Mediated Methylation Signatures In Colorectal Cancers And Polyps
Funder
National Health and Medical Research Council
Funding Amount
$457,076.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. We hypothesise that there are different types of bowel cancer depending on different genes that can be inactivated abnormally, and these subgroups have different clinical features and responses to therapy. We aim to identify the major gene changes that characterise these subgroups, which will in the future allow the development of gene markers for early detection as well as the possibility of individualised patient therapy.
Wnt And MAPK Signalling In The Determination Of Colorectal Neoplasia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$397,179.00
Summary
Polyps are growths in the bowel that may progress to become a bowel cancer. To prevent the development of cancer, these polyps must be removed by timely colonoscopy. There are many different types of bowel polyps, and these are associated with distinct genetic changes and likelihood of recurrence. This study aims to better understand the DNA changes that occur in bowel polyps and how these impact the clinical features of the polyps. In the future this will aid detection and surveillance strategi ....Polyps are growths in the bowel that may progress to become a bowel cancer. To prevent the development of cancer, these polyps must be removed by timely colonoscopy. There are many different types of bowel polyps, and these are associated with distinct genetic changes and likelihood of recurrence. This study aims to better understand the DNA changes that occur in bowel polyps and how these impact the clinical features of the polyps. In the future this will aid detection and surveillance strategies.Read moreRead less
In Vivo Models For Understanding The Cellular And Molecular Pathogenesis Of Barrett's Oesophagus
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce th ....The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce the normal layered structure of the human oesophageal lining in the laboratory and we propose to use these models to address key issues in the biology of Barrett's oesophagus. In aim 1, we wish to determine if the cells in patients with Barrett's have been permanently, or only transiently, altered and to understand the role of gastric acid- bile and accessory cells in this transformation. In aim 2 we will look more closely at the molecular changes that drive the cellular transformation characteristic of Barrett's. We will do this by manipulating the expression of selected genes in human oesophageal cells and assessing the effects of these genes on cell growth and differentiation using our cell culture models. The results of these studies will pave the way for the design of appropriate clinical strategies to treat Barrett's oesophagus and prevent the progression of this premalignant condition to oesophageal adenocarcinoma.Read moreRead less
Studies Of Genetic Predisposition To Develop Serrated Neoplasia In The Colorectum.
Funder
National Health and Medical Research Council
Funding Amount
$308,291.00
Summary
Colorectal Cancer was once believed to develop only from a certain kind of polyp in the colon called the adenoma. However, recently another type of polyp called the hyperplastic polyp was found to also be capable of producing a cancer. In this proposal, we will look at the possibility that the predisposition to form hyperplastic polyps may be inherited in families.
Clinical And Microbiological Studies Of Faecal Microbiota Transplantation In Ulcerative Colitis - A Phase II, Multicentre, Randomised Double Blind, Exploratory Proof Of Concept, Placebo Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct ....Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct the inappropriate immune system activation.Read moreRead less