I am a clinician-scientist engaged in basic, translational and clinical breast cancer research, with the long-term goal to identify and exploit novel cancer targets to improve patient outcomes. My research, which covers both sporadic and hereditary forms of breast cancer, is focussed on elucidating the breast epithelial cell hierarchy, in order to identify key regulators responsible for breast epithelial cell proliferation, differentiation and cancer.
I am a cellular biologist studying lineage commitment and differentiation in the mammary gland. Key interests include defining transcriptional regulators that are important for mammary gland development and oncogenesis, and the characterisation of stem cells and other epithelial cell types in breast tissue.
I am a cellular biologist studying lineage commitment and differentiation in the mammary gland. Key interests include defining transcriptional regulators that are important for mammary gland development and oncogenesis, and the characterisation of normal
Isolation And Characterisation Of Mouse Mammary Stem And Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$540,202.00
Summary
We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell ....We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell population is expanded in at least one model of mammary tumours, suggesting that some tumours may arise from the breast stem cell itself. Using mouse models and cellular assays, our aim is to characterise, for the first time, the hierarchy of stem, progenitor ('daughter cells') and mature cells in the mammary gland. These studies will provide insight into the various cell types that give rise to different types of breast cancer. An important evolving concept in cancer biology is that a rare population of cells resident within a tumour, termed 'cancer stem cells', have indefinite growth potential and drive tumour growth. These cells could even account for resistance to conventional anti-cancer treatment, as cells with stem cell-like properties would be able to proliferate extensively and form new tumours. We will apply our knowledge of normal mammary stem cells to determine whether cancer stem cells are indeed present in mouse tumours. Those findings will have direct relevance to human breast cancer. Utlimately, we wish to identify specific cell surface proteins on stem and precursor cells that could provide therapeutic targets. Our studies will provide new insights into the cell types from which breast cancer arise, and how their fate and tumour-forming capacity can be modified by altering gene expression. Delineation of cancer-prone cells and cancer stem cells could reveal new markers and provide new therapeutic strategies to target breast cancer.Read moreRead less
Elucidating The In Vivo Role Of The Pro-survival Gene Mcl-1 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$664,691.00
Summary
Breast cancer strikes one in 8 women by age 85 and is a major cause of morbidity and mortality. Despite recent improvements, the immense breast cancer burden demands new strategies that will radically improve patient outcomes. This project will address a hallmark of cancer: evasion of apoptosis. Understanding the molecular events that promote tumour survival and resistance to therapy represents a key area in cancer biology that has yet to be properly applied to breast cancer.
Cell Survival Pathways As Potential Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$142,914.00
Summary
Cancer cells are characterised by their capacity for relentless growth, survival and evasion of cell death. This proposal will use patient derived xenograft models of primary breast cancer to test the hypothesis that addition of BH3-mimetics could improve response to anti-HER2 therapy. This technique involves transplantation of patient tumours into immune-compromised mice. This represents a useful method for testing new agents.
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.