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.
The Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse heart disease.
Is Mitochondiral STAT3 Necessary For K-Ras Induced Myeloid Leukaemias?
Funder
National Health and Medical Research Council
Funding Amount
$425,326.00
Summary
Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dep ....Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dependent metabolic changes in ML.Read moreRead less
Neural Control Of Renin Expression By MicroRNA In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$805,972.00
Summary
We identified that mice bred to have high blood pressure have an overactive nervous system that affects a gene that controls a hormone in the kidney that increases blood pressure. The proposal will determine the effects of a novel treatment to alter the gene to reverse the changes in the kidney and thereby normalizing blood pressure. This will lead to new therapy and reduce the major risk factor of cardiovascular disease.
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
Maternal Recognition Of Fetal Sex In The Regulation Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$455,821.00
Summary
Preterm birth is the largest cause of death in infants and males are more likely to be born preterm than females. We propose that the intrauterine renin-angiotensin system, the activity of which is regulated in a sex-specific manner, plays a critical role in protecting against preterm labour. Our study will further our understanding of the mechanisms of preterm labour and provide new insight into the sex-specific differences in the prevalence of preterm birth.
Identification Of Novel Tumour Suppressors In Ras-mediated Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$580,504.00
Summary
Cancer is a cooperative process, involving mutations in several genes. Activation of the signaling protein, Ras, contributes to ~30% of human cancers, but alone is not sufficient for tumour formation. The identification of cooperating Tumour Suppressors (TSs), and their analysis in the vinegar fly, Drosophila, mammalian cells and mouse models is key to understanding cancer progression and for the development of therapeutic regimes
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
Regulation Of The Placental Renin-angiotensin System By MicroRNAs; Implications For Pregnancies Complicated By Placental Insufficiency?
Funder
National Health and Medical Research Council
Funding Amount
$483,058.00
Summary
Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their ea ....Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their early detection.Read moreRead less