The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
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.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.
Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
Functional Studies On The Role Of DNp73 In Stem Cells And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$428,838.00
Summary
This project investigates the role of the p73 gene in regulating stem cells and facilitating intestinal cancer formation. We hypothesize that when a particular form of this gene (DNp73) is upregulated it prevents differentiation of stem cells and promotes tumour formation. We combine novel approaches in mice and fruit flies to examine the function of DNp73 in stem cells with analysis of human tumour samples. These studies may identify a new target for tumour therapy.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.