Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
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.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Roles For Gastrin And Hypoxia In Colorectal Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
Our objective is to understand how hormones such as gastrin stimulate the development of colorectal cancer. Our preliminary data shows that the amount of gastrin produced by tumour cells is increased by low oxygen. We will therefore study how the increase in gastrin in response to low oxygen causes a compensatory growth of the tumour. The ability to interfere with this process should allow us to slow tumour growth.
Molecular And Therapeutic Interactions In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$670,409.00
Summary
This project will use our unique preclinical models to unravel the molecular and cellular events underlying the cooperation between two important cancer-causing pathways, PI3K and Apc/Wnt, in driving the development of cancer in the gastrointestinal tract. Our studies will provide critical new insights into the clinical significance of this interaction as well as the potential role of these pathways in the prophylactic and therapeutic actions of aspirin in the context of colorectal cancer.
Elucidating The Role Of Claudin-2 In Tumour Initiation And Metastasis Development From Colorectal Cancer: Consequence For Tumour Relapse
Funder
National Health and Medical Research Council
Funding Amount
$398,993.00
Summary
Mortality from colorectal cancer is often due to the development of metastases. Cancer stem cells (CSC) are suspected to provide a major drive for metastasis development, to resist current therapies, and to initiate tumour relapse. Yet, little is known about mechanisms that control CSC behaviour. Our project investigates the role of claudin-2, a cell adhesion protein that is strongly overexpressed in colorectal cancer, in the regulation of CSCs, metastasis development and tumour relapse.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Investigating Tumour Initiation And Growth In A Panel Of Mice Defective In Epigenetic Reprogramming.
Funder
National Health and Medical Research Council
Funding Amount
$421,600.00
Summary
Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatme ....Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatments in humans.Read moreRead less
Microtubule Cytoskeleton In Tumourigenesis And Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
Over one million cases of lung cancer are diagnosed each year worldwide, making this the leading cause of cancer death. Advanced non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases. We have identified a protein called ?III-tubulin that is often highly expressed in aggressive and drug resistant NSCLC, and is involved in tumour formation. We will examine how ?III-tubulin is working and identify ways to target this protein to stop tumour growth.