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
I am a medical epidemiologist investigating links between specific infectious agents and specific types of cancer in immune deficient populations. Through the exploration of these relationships, my research aims to allow the prevention of these types of c
Acute myeloid leukaemia (AML) is a major health problem with only about one third of patients being cured. In addition therapies have changed little over the last 20 years. However there is optimism that with greater knowledge of the biochemical changes in AML that are caused by genetic mutations, more effective treatments will be developed. This project therefore aims to increase understanding of the biochemical interplay between two proteins called c-Cbl and Flt3 that are altered in AML.
Activated Dendritic Cell Monoclonal Antibodies As Therapeutics To Prevent Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies i ....A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies in mice that react with human activated dendritic cells and prevent them from inducing immune responses in the test-tube. These antibodies are also likely to be effective in patients, but cannot be used in their present form because mouse antibodies induce an undesirable immune response in humans. We therefore plan to convert them to resemble human antibodies (antibody engineering). Antibodies that react with other types of cell in the body are already used to treat or prevent a variety of conditions, including graft versus host disease, but no one has developed a therapeutic antibody against activated dendritic cells. We are applying to the NHMRC for funding to engineer our antibodies and to test them in test tube experiments and also in mouse models of graft versus host disease. We also plan to study the changes in blood levels of activated dendritic cells in bone marrow transplnt patients. This will provide information on the best time to use our new therapeutic antibodies to prevent graft versus host disease. The aim of this grant application will have been achieved if, after three years, we have a new antibody ready for testing in bone marrow transplant patients.Read moreRead less
Regulatory Dendritic Cells For The Prevention And Treatment Of Graft-versus-Host Disease.
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. These studies will focus on the ability of a newly defined type of white blood called a regulatory dendritic cell to prevent this complication and avoid the requirement for BMT patients to take drugs that suppress their immune system.Read moreRead less